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Completed

NCT Number: NCT02401828

The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial

48-week open label randomized phase IV investigator initiated intervention study. The purpose of this study is to evaluate whether HIV-1 suppression can be maintained by DTG monotherapy in HIV-1 infected, virologically suppressed patients on cART.

104 adults fulfilling the in and exclusion criteria and on stable cART will be randomized over 2 investigational arms.

The first arm will contain the direct switch population. This population will switch directly from stable cART to Dolutegravir mono-therapy on baseline visit.

The second arm will contain the delayed-switch population. This group will switch from stable cART to Dolutegravir monotherapy 24 weeks after baseline visit.

The main goal is to investigate if Dolutegravir mono-therapy could be non-inferior to cART in virological suppressed HIV-1 infected adults.

If a interim analysis (performed when 40 patients on dolutegravir monotherapy have passed week 12) shows that it is safe to continue the study, an additional 30 patients will be included on top of the 104 patients needed for the primary endpoint analysis. In contrast to the primary endpoint population, these additional 30 patients will have a CD4 nadir <200 but a CD4 >350 at the time of the screening visit. Besides that, these 30 patients will have to fulfill all other in and exclusion criteria of the primary endpoint population (specifically a viral load never >100.000). These 30 patients are part of a pilot study looking at the possibility to broaden the eligible population in a future larger randomized clinical trial.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Erasmus Medical Center

Rotterdam, South Holland, 3000 CA, Netherlands

About this study

DTG Monotherapy will be considered non-inferior to cART if the lower bound of the one sided 97.5%CI for the difference in proportion of patients reaching the primary endpoint is not lower than -12%. For this purpose, a sample size of 52 per arm would provide 80% power at alpha 0.025 to establish non-inferiority of DTG monotherapy compared with cART when the primary endpoint success rate is 95% in both treatment arms.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Documented HIV-1 positive by ELISA or Western Blot or Plasma HIV-RNA >1000 c/ml.
  • 18 years or older.
  • HIV-RNA ≤50 copies/mL for ≥24 weeks.
  • Historical baseline HIV-RNA plasma load <100.000 c/ml
  • CD4 count nadir pre-cART ≥200 cells/mm3
  • Not on strong UGT1A1 or CYP3A4 inducing agents as stated in DTG SPC.
  • General medical condition does not interfere with trial procedures (on investigators' discretion)
  • Females should have no plans of becoming pregnant during the next 18 months after the baseline visit
  • Females are eligible if:
  • They do not plan to become pregnant during the study
  • Negative screening pregnancy test and uses one of the following methods: 1.Abstinence from penile/vaginal intercourse during the study; 2.Double barrier contraceptive methods 1 of which must be condom.

Exclusion criteria

  • Previous virological failure on any ART.
  • Patient without documented anti-HBs antibodies.
  • Subjects positive for hepatitis B at screening (HBsAg+).
  • Any documented genotypic HIV-1 resistance with at least low-level resistance according to stanford HIV drug resistance database
  • No record of the historical baseline plasma viral load available
  • Subjects with concomitant CDC-C opportunistic infections within 90 days of screening.
  • Subjects with history of allergy to INI.
  • Subjects with creatinine clearance <50mL/min according to CKD-EPI.
  • Subjects with hepatic impairment of at least Child-Pugh B.
  • Exposure to experimental drug or experimental HIV-1 vaccine within 90 days of start of DTG.
  • Screening ALT >5x ULN or ALT>3xULN and bilirubin >2 ULN.
  • Patient (man or woman) planning or hoping to conceive a child/become pregnant during the study
  • Patients who cannot take DTG 2 hours before or 6 hours after antacids, calciumcarbonate or iron supplements.

Treatment and study plan

Dolutegravir

Drug

Switch from combination antiretroviral therapy to dolutegravir monotherapy

Other names: Tivicay, S/GSK1349572

Primary outcomes

  1. Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population

    Time frame: 24 weeks

    HIV-RNA <200c/ml at week 24 after baseline

Secondary outcomes

  1. Time to loss of virological response (TLOVR) in the OT population

    Time frame: 1 week

    Time to first of two confirmed HIV-RNA >50c/ml at least 1 week apart

  2. Efficacy of dolutegravir monotherapy in maintaining virological suppression in the entire study population (ITT)

    Time frame: 24 weeks

    HIV-RNA <200c/ml at week 24 after baseline

  3. Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population

    Time frame: 48 weeks

    HIV-RNA <50 & <200 at week 24 & 48

  4. Evaluate safety of Dolutegravir monotherapy (Acquired resistance & Adverse Events according to CDC 4.0)

    Time frame: 60 weeks

    Acquired resistance & Adverse Events according to CDC 4.0

  5. Evaluate the evolution of CD4 associated HIV-1 reservoir

    Time frame: 48 weeks

    Total/integrated HIV-DNA & 2LTR

  6. Evaluate the number and type of INI resistance mutation in patients with virological failure

    Time frame: 48 weeks

    Virological failure: HIV-RNA >200c/ml

  7. Evaluate CD4 cell count change

    Time frame: 48 weeks

    Compare baseline vs. 48 weeks after baseline

  8. Evaluate changes in renal function after 24 and 48 weeks of dolutegravir monotherapy

    Time frame: 48 weeks

  9. Cost effectiveness of DTG monotherapy

    Time frame: 48 weeks

    Cost per QALY during DTG monotherapy in comparison with the costs of therapy with the patient's own cART regimen used before study inclusion

  10. Evaluate change in BMD after 24 and 48 weeks of dolutegravir mono-therapy

    Time frame: 48 weeks

  11. Exploratory analysis of blood pressure, weight, BMI, fasting serum lipids, Framingham risk score, ATP-III treatment goals and inflammatory markers after 24wks of dolutegravir mono-therapy

    Time frame: 48 weeks

  12. Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population

    Time frame: 12 weeks

    HIV-RNA <200c/ml and <50 at week 12 after baseline

Sponsors and collaborators

Lead sponsor

Erasmus Medical Center

Other

Registry information

Acronym: DOMONO

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Mar 30, 2015
Registry last updated
Jan 28, 2020

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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