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Completed

NCT Number: NCT02429791

Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-1)

The aim of this study was to determine if virologically suppressed human immunodeficiency virus type 1 (HIV-1) infected adults on an antiretroviral regimen (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to a two-drug regimen with dolutegravir (DTG) + rilpivirine (RPV). The study primarily assessed the non-inferiority antiviral activity of switching to DTG + RPV once daily compared to continuation of current antiretroviral regimen (CAR) up to Week 48 with a switch visit for eligible subjects in the CAR group to initiate DTG + RPV therapy at Week 52. CAR included 2 NRTIs plus 1 HIV-1 integrase inhibitor (INI), or 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 protease inhibitor (PI). The study included a 148-week open-label treatment phase, comprising of an Early Switch Phase (Day 1 to Week 52) and a Late Switch Phase (Week 52 to Week 148). The participants fulfilling the study eligibility criteria participated in the Early Switch Phase where they either switched from their CAR to DTG + RPV, or continued taking their CAR, until Week 52. At the end of Early Switch Phase, eligible participants proceeded to the Late Switch Phase where all participants in both DTG + RPV and CAR treatment groups received DTG + RPV therapy until Week 148. After Week 148, eligible subjects were given the opportunity to continue receiving DTG +RPV, in the Continuation Phase.

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

GSK Investigational Site, Ciudad Autonoma de Buenos Aire, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants must have been able to understand and comply with protocol requirements, instructions, and restrictions.
  • Participants must have been likely to complete the study as planned.
  • Participants must have been considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country, etc.).
  • HIV-1 infected men or women of greater than or equal to (>=)18 years of age.
  • Must have been on uninterrupted current regimen (either the initial or second combination antiretroviral therapy [cART] regimen) for at least 6 months prior to screening; Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification. Acceptable stable cART regimens prior to screening include 2 NRTIs plus INI (either the initial or second cART regimen), or an NNRTI (either the initial or second cART regimen), or a Boosted PI (or atazanavir unboosted) (either the initial or second PI-based cART regimen).
  • Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening;
  • Plasma HIV-1 RNA <50 c/mL at Screening;
  • A female may have been eligible to enter and participate in the study if she was of : Non-child-bearing potential either defined as post-menopausal (12 months of spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, Child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: Complete abstinence from intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications and completion of the Follow-up visit; Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion); Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study and this male is the sole partner for that participant; The documentation on male sterility could come from the site personnel's review of participant's medical records, medical examination, and/or semen analysis, or medical history interview provided by her or her partner; Approved hormonal contraception for participants randomly assigned to DTG + RPV arm (and for participants randomly assigned to CAR following switch to DTG + RPV at Week 52) or approved hormonal contraception plus a barrier method for participants assigned to CAR through Week 52; Approved hormonal contraception included: Combined estrogen and progestogen oral contraceptive, Contraceptive subdermal implant, Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches. Any other method with published data showing that the expected failure rate is <1% per year. Any contraception method must have been used consistently, in accordance with the approved product label during treatment with study drug and for at least 2 weeks after discontinuation of study drug and completion of the Follow-Up Visit. The investigator was responsible for ensuring that participants understand how to properly use these methods of contraception. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception.
  • Participants who were willing and able to understand requirements of study participation and provided signed and dated written informed consent prior to screening.
  • For participants enrolled in France: participants were eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion criteria

Exclusionary Criteria prior to screening or Day 1:

  • Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >=50 c/mL.
  • Within the 6 to 12 month window prior to screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.
  • Within the 6 to 12 month window prior to screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements >=50 c/mL.
  • Any drug holiday during the window between initiating first HIV ART and 6 months prior to screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
  • Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement >=400 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen).

Exclusionary medical conditions:

  • Women who were pregnant, breastfeeding or planned to become pregnant or breastfeed during the study.
  • Any evidence of an active Centers for Disease Control and Prevention Category C disease. Exceptions included cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of <200 cells per cubic millimeter (cells/mm^3).
  • Participants with severe hepatic impairment (Class C) as determined by Child-Pugh Classification.
  • Unstable liver disease (as defined by the presence of any of the following: ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), and Hepatitis B surface antibody (HBsAb) as follows: Participants positive for HBsAg were excluded; Participants positive for anti-HBc (negative HBsAg status) and negative for HBsAb were excluded.
  • Participants with an anticipated need for any Hepatitis C virus (HCV) therapy during the Early Switch Phase and for interferon-based therapy for HCV throughout the entire study period.
  • History or presence of allergy to the study drugs or their components or drugs of their class;
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to randomization;
  • Participants who in the investigator's judgment posed a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should have been considered when evaluating for suicide risk;
  • Any pre-existing physical or mental condition which, in the opinion of the Investigator, could have interfered with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which could have compromised the safety of the participants;
  • Any condition which, in the opinion of the Investigator, could have interfered with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to take oral medication;

Exclusionary Treatments prior to Screening or Day 1:

  • Use of medications which were associated with Torsades de Pointes.
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
  • Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses.
  • Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to Day 1 of this study.
  • Participants who were participating or anticipated to be selected to participate in any other interventional study, with the exception of the DEXA sub-study 202094, after randomization
  • A history of use of any regimen consisting of only single NNRTI therapy (even if only for peri-partum treatment), or only single or dual NRTI therapy prior to starting cART.
  • Current or prior history of etravirine (ETR) use.
  • Current use of tipranavir/ritonavir or fosamprenavir/ritonavir.
  • Participants receiving any prohibited medication and who were unwilling or unable to switch to an alternate medication.

Exclusionary Laboratory Values or Clinical Assessments at Screening:

  • Evidence of viral resistance based on the presence of any resistance associated major PI, INI, NRTI, or NNRTI mutation and integrase (IN) resistance associated substitution R263K in any available prior resistance genotype assay results.
  • Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities. A single repeat test was allowed during the Screening period to verify a result.
  • Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
  • Alanine aminotransferase (ALT) >=5 × upper limit of normal (ULN), or ALT >=3 × ULN and bilirubin >=1.5 × ULN (with greater than [>] 35% direct bilirubin).
  • Corrected QT interval (QTc [Bazett]) >450 milliseconds or QTc (Bazett) >480 milliseconds for participants with bundle branch block. The QTc was the QT interval corrected for heart rate according to Bazett's formula (QTcB).

Treatment and study plan

DTG 50 mg

Drug

Participants received one oral tablet of 50 mg DTG daily administered concomitantly with RPV. Each DTG tablet contained 52.62 mg dolutegravir sodium salt, which was equivalent to 50 mg dolutegravir free acid.

RPV 25 mg

Drug

Participants received one oral tablet of 25 mg RPV daily administered concomitantly with DTG along with a meal. Each RPV tablet contained 27.5 mg of rilpivirine hydrochloride, which was equivalent to 25 mg of RPV.

CAR

Drug

CAR included the following combinations: 2 NRTIs + 1 INI, 2 NRTIs + 1 NNRTI, or 2 NRTIs + 1 PI

Primary outcomes

  1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm

    Time frame: Week 48

    Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG + RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.

    Plasma samples were collected for quantitative analysis of HIV-1 RNA.

Secondary outcomes

  1. Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Weeks 24 and 48

    Time frame: At Weeks 24 and 48

    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  2. Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 24 Using Snapshot Algorithm

    Time frame: Week 24

    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity of DTG + RPV once daily compared to continuation of CAR. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA.

  3. Number of Participants With Common Non-serious Adverse Event (AE), Any Serious AE (SAE), AE of Maximum Toxicity Grade 1, 2, 3 or 4 and AE Leading to Discontinuation (AELD)

    Time frame: Up to Week 411 or study discontinuation

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize participant or may require medical or surgical intervention were categorized as SAE. AEs were graded as per Division of Acquired Immunodeficiency Syndrome (DAIDS) grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Common AEs were those with >5% incidence for either treatment.

  4. Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks

    Time frame: Up to 48 weeks

    Blood samples were collected to evaluate alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, blood urea nitrogen (BUN), total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-Baseline in clinical chemistry over 48 weeks was summarized. Clinical chemistry toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a chemistry toxicity.

  5. Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities Over 48 Weeks

    Time frame: Up to 48 weeks

    Blood samples were collected to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count and platelet count. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-Baseline in hematology over 48 weeks was summarized. Hematology toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a hematology toxicity.

  6. Mean Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess hs-CRP. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  7. Mean Change From Baseline in Cystatin C at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess cystatin C. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  8. Mean Change From Baseline in D-Dimer at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess D-Dimer. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  9. Mean Change From Baseline in Fatty Acid Binding Protein 2 (FABP) and Soluble Cluster Designation (CD)14 at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess FABP and soluble cluster designation (CD)14. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  10. Mean Change From Baseline in Soluble CD163 and Oxidized Low Density Lipoprotein (LDL) at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess soluble CD163 and oxidized LDL. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  11. Mean Change From Baseline in Retinol Binding Protein (RBP), Serum Creatinine and Glucose at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess RBP, serum creatinine and glucose. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  12. Mean Change From Baseline in Urine Phosphate at Week 48

    Time frame: At Week 48

    Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine phosphate. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  13. Mean Change From Baseline in Beta-2-microglobulin (B2M) (Blood and Urine), Urine RBP and 25 Hydroxy-vitamin D (Blood) at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess B2M and 25 hydroxy-vitamin D. Urine samples were collected to assess B2M and RBP. Change from Baseline was calculated as value at indicated time point minus Baseline value. For 25 hydroxy-vitamin D, analysis of changes from Baseline was performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.

  14. Mean Change From Baseline in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio at Week 48

    Time frame: At Week 48

    Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine albumin/creatinine ratio and urine protein/creatinine ratio. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  15. Mean Change From Baseline in Bone-specific Alkaline Phosphatase, Procollagen 1 N-terminal Propeptide, Osteocalcin, Type I Collagen C-Telopeptides and Soluble Vascular Cell Adhesion Molecule (sVCAM) at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type I Collagen C-Telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. For bone-specific alkaline phosphatase, procollagen 1-N-propeptide, osteocalcin and type 1 collagen C-telopeptide, analyses of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.

  16. Mean Change From Baseline in Interleukin 6 (IL-6) at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess IL-6. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  17. Mean Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Week 48

    Time frame: At Week 48

    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess insulin resistance. Change from Baseline was calculated as value at indicated time point minus Baseline value. The homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) index, the product of basal glucose and insulin levels divided by 22.5 (1,2), is regarded as a simple, inexpensive, and reliable surrogate measure of insulin resistance.

  18. Mean Change From Baseline in Fasting Lipids at Weeks 24 and 48

    Time frame: At Week 24 and at Week 48

    Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  19. Number of Participants With Genotypic Resistance- Early Switch Phase

    Time frame: Up to Week 52

    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (Rilpivirine [RPV], Dolutegravir [DTG], Emtricitabine [FTC], Tenofovir [TDF], Darunavir/r [DRV/r]) in participants Meeting CVW Criteria has been presented.

  20. Number of Participants With Genotypic Resistance-DTG+RPV Group Through Early and Late Switch Phase

    Time frame: Up to Week 148

    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, Elvitegravir [EVG], Raltegravir [RAL], Delavirdine [DLV], Efavirenz [EFV], Etravirine [ETR], Nevirapine [NVP], RPV, Lamivudine [3TC], Abacavir [ABC], FTC, TDF, Zidovudine [ZDV], Stavudine [d4T], Didanosine [ddI], Atazanavir/r [ATV/r], DRV/r, Fosamprenavir/r [FPV/r], Indinavir/r [IDV/r], Lopinavir/r [LPV/r], Nelfinavir [NFV], Ritonavir [RTV], Saquinavir/r [SQV/r], Tipranavir/r [TPV/r]) in participants Meeting CVW Criteria has been presented.

  21. Number of Participants With Genotypic Resistance-CAR Group Through Late Switch Phase

    Time frame: Post-Late switch (LS) Baseline (Week 52) up to Week 148

    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented.

  22. Number of Participants With Phenotypic Resistance-Early Switch Phase

    Time frame: Up to Week 52

    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, RAL, EVG, RPV, ETR, 3TC, ABC, FTC, TDF, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented.

  23. Number of Participants With Phenotypic Resistance-DTG+RPV Group Through Early and Late Switch Phase

    Time frame: Up to Week 148

    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented.

  24. Number of Participants With Phenotypic Resistance-CAR Group Through Late Switch Phase

    Time frame: Post-LS Baseline (Week 52) up to Week 148

    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented.

  25. Pre-dose Concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in Participants Switching to DTG + RPV-DTG+RPV Group Through Early and Late Switch Phase

    Time frame: Pre-dose at Week 4, 24, 48, 56, 76 and 100

    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24, 48, 56, 76, and 100. Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the early + late switch phase.

  26. Pre-dose Concentrations of DTG and RPV at Weeks 56, 76 and 100 in Participants Switching to DTG+RPV-CAR Group Through Late Switch Phase

    Time frame: Pre-dose at Weeks 56, 76 and 100

    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 56, 76, and 100. Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the late switch phase.

  27. Pre-dose Concentrations of DTG and RPV at Weeks 2, 4 and 8 in the First 20 Participants Who Switch From Efavirenz (EFV) or Nevirapine (NVP) to DTG + RPV

    Time frame: Pre-dose at Week 2, 4 and 8

    Two blood samples were collected pre-dose for DTG and RPV at Weeks 2,4 and 8 only for the first 20 participants who switch from EFV or NVP to DTG + RPV. One blood sample was collected pre-dose for EFV or NVP at Week 2 for the first 20 participants who switch from EFV or NVP to DTG + RPV.

  28. Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm by Baseline Third Agent Treatment Class

    Time frame: Week 48

    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the FDA snapshot algorithm was assessed by Baseline third agent class to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy of DTG +RPV compared to continuation of CAR. Plasma samples were collected for quantitative analysis of HIV-1 RNA. The analysis was done using Cochran-Mantel Haenszel test stratified by current antiretroviral third-agent class and age group.

  29. Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Week 48 by Baseline Third Agent Treatment Class

    Time frame: At Week 48

    Blood samples were collected for CD4 cell count assessment by flow cytometry was carried out to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Value at Day 1 was considered as Baseline. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  30. Number of Participants With Any AE, AELD or AE With Grade 1, 2, 3 or 4 Toxicity Over 48 Weeks by Baseline Third Agent Treatment Class

    Time frame: Up to 48 weeks

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any AE, AELD or AE with maximum grade toxicity experienced by any one participant over 48 weeks by Baseline third agent class (INI, NNRTI, or PI) was summarized. AEs were graded as per DAIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.

  31. Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class

    Time frame: Up to 48 weeks

    Blood samples were collected to evaluate ALT, albumin, ALP, AST, total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, BUN, total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value at Day 1 was considered as Baseline. Number of participants who experienced maximum toxicity grade post-Baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INI, NNRTI, PI) was summarized. Clinical chemistry toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.

  32. Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class

    Time frame: Up to 48 weeks

    Blood samples were collected to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Value at Day 1 was considered as Baseline. Number of participants who experienced maximum toxicity grade post-Baseline in hematology parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized. Hematology toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.

  33. Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class

    Time frame: Up to Week 48

    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were to be collected at Day 1. Number of participants with genotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome has not been analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.

  34. Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class

    Time frame: Up to Week 48

    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were to be collected at Day 1. Number of participants with phenotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome was not analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.

  35. Change From Baseline in Fasting Lipids at Weeks 24 and 48 by Baseline Third Agent Treatment Class

    Time frame: At Week 24 and at Week 48

    Blood samples were collected at Baseline (Day 1), Weeks 24 and 48 to assess fasting lipids which included total cholesterol (CHO), LDL cholesterol, HDL cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  36. Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase

    Time frame: At Week 4, Week 24 and Week 48

    Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in participant. Symptom count is the sum of number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is unweighted sum of the bother item scores for each symptom. Symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). Last observation carried forward (LOCF) was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value. Day 1 was considered as Baseline value.

  37. Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV Group Through Early and Late Switch Phase

    Time frame: At Week 56, Week 76, Week 100 and Week 148

    Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in participant. Symptom count is the sum of number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is unweighted sum of the bother item scores for each symptom. Symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score).

    LOCF was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value. Day 1 was considered as Baseline value.

  38. Change From LS Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 56, 76, 100 and 148-CAR Group Through Late Switch Phase

    Time frame: At Week 56, Week 76, Week 100 and Week 148

    Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in participant. Symptom count is the sum of number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is unweighted sum of the bother item scores for each symptom. Symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). LOCF was used as primary method of analysis. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value. Value at Week 48 was considered as LS Baseline value.

  39. Change From Baseline Treatment Satisfaction Using the HIV Treatment Satisfaction Questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase

    Time frame: At Week 4, Week 24 and Week 48

    HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  40. Change From Baseline Treatment Satisfaction Using HIV TSQ at Weeks 56, 76, 100 and 148 - DTG+RPV Group Through Early and Late Switch Phase

    Time frame: At Week 56, Week 76, Week 100 and Week 148

    HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  41. Change From LS Baseline Treatment Satisfaction Using HIV TSQ at Weeks 56, 76, 100 and 148-CAR Group Through Late Switch Phase

    Time frame: At Week 56, Week 76, Week 100 and Week 148

    HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Value obtained at Week 48 was considered as LS Baseline value. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value.

  42. Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class-DTG+RPV Group Through Continuation Phase

    Time frame: Up to Week 411

    For all participants who met virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were collected at Day 1. Number of participants with genotypic resistance to DTG or RPV for those meeting virologic withdrawal criteria in subgroups, stratified based on baseline third agent treatment class (NNRTI, INI, PI) were summarized.

  43. Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class-DTG+RPV Group Through Continuation Phase

    Time frame: Up to Week 411

    For all participants who met virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were collected at Day 1. Number of participants with phenotypic resistance to DTG or RPV for those meeting virologic withdrawal criteria in subgroups, stratified based on baseline third agent treatment class (NNRTI, INI, PI) were summarized.

  44. Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class- CAR Group Through Continuation Phase

    Time frame: Week 52 to Week 411

    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were analyzed in an attempt to obtain genotype data on as many samples as possible. Number of participants with genotypic resistance to CAR for those meeting virologic withdrawal criteria in subgroups, stratified based on baseline third agent treatment class (INI) were summarized.

  45. Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class- CAR Group Through Continuation Phase

    Time frame: Week 52 to Week 411

    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were analyzed in an attempt to obtain phenotype data on as many samples as possible. Number of participants with phenotypic resistance to CAR for those meeting virologic withdrawal criteria in subgroups, stratified based on baseline third agent treatment class (INI) were summarized.

  46. Number of Participants With Genotypic Resistance-DTG+RPV Group Through Continuation Phase

    Time frame: Up to Week 411

    Plasma samples were collected for participants meeting the CVW criteria (previous plasma HIV-1 RNA >=50 c/mL and current plasma HIV-1 RNA >= 200 c/mL) to evaluate any potential genotypic evolution of resistance. Genotypic resistance data for the following drugs was presented: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r.

  47. Number of Participants With Phenotypic Resistance-DTG+RPV Group Through Continuation Phase

    Time frame: Up to Week 411

    Plasma samples were collected for participants meeting the CVW criteria (previous plasma HIV-1 RNA >=50 c/mL and current plasma HIV-1 RNA >= 200 c/mL) to evaluate any potential phenotypic evolution of resistance. Phenotypic resistance data for the following drugs was presented: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r.

  48. Number of Participants With Genotypic Resistance-CAR Group Through Continuation Phase

    Time frame: Week 52 to Week 411

    Plasma samples were collected for participants meeting the CVW criteria (previous plasma HIV-1 RNA >=50 c/mL and current plasma HIV-1 RNA >= 200 c/mL) to evaluate any potential genotypic evolution of resistance. Genotypic resistance data for the following drugs was presented: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r.

  49. Number of Participants With Phenotypic Resistance- CAR Group Through Continuation Phase

    Time frame: Week 52 to Week 411

    Plasma samples were collected for participants meeting the CVW criteria (previous plasma HIV-1 RNA >=50 c/mL and current plasma HIV-1 RNA >= 200 c/mL) to evaluate any potential phenotypic evolution of resistance. Phenotypic resistance data for the following drugs was presented: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r.

Other outcomes

  1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 Using the Snapshot Algorithm-DTG+RPV Group Through Early and Late Switch Phase

    Time frame: At Weeks 100 and 148

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.

  2. Change From Baseline in CD4+ Lymphocyte Count at Weeks 100 and 148-DTG+RPV Group Through Early and Late Switch Phase

    Time frame: At Weeks 100 and 148

    Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  3. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 Using the Snapshot Algorithm-CAR Group Through Late Switch Phase

    Time frame: At Weeks 100 and 148

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.

  4. Change From LS Baseline in CD4+ Lymphocyte Count at Weeks 100 and 148-CAR Group Through Late Switch Phase

    Time frame: At Weeks 100 and 148

    Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value.

Sponsors and collaborators

Lead sponsor

ViiV Healthcare

Industry

Collaborators

  • GlaxoSmithKline
  • Janssen Pharmaceuticals

Registry information

Official study title

A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Dolutegravir Plus Rilpivirine From Current INI-, NNRTI-, or PI-based Antiretroviral Regimen in HIV-1-Infected Adults Who Are Virologically Suppressed

Important dates

Study start
2015
Primary completion
2016
Study completion
2023
First posted
Apr 29, 2015
Registry last updated
Sep 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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