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NCT Number: NCT04375800

Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Aged 4 Weeks to <12 Years and <45 kg (MK-1439-066)

This is a single-group, open-label, multi-site study in pediatric participants with human immunodeficiency virus type 1 (HIV-1) infection, aged 4 weeks to <12 years and weighing <45 kg, who are treatment-naive (TN) or have been virologically suppressed (VS) on stable combination antiretroviral therapy (cART) for ≥3 months with no history of treatment failure. The primary objectives are:

* To evaluate the steady state pharmacokinetics (PK) of doravirine (DOR) [MK-1439] when given in combination with 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) or as part of the fixed-dose combination (FDC) of DOR/lamivudine (3TC)/tenofovir disproxil fumarate (TDF) in participants ≥6 to <12 years and weighing ≥14 to <45 kg. * To evaluate the safety and tolerability of DOR when given with 2 NRTIs or as part of the FDC of DOR/3TC/TDF, in participants ≥6 to 12 years and weighing ≥14 to <45 kg, through Week 24.

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Key information

Conditions

Human Immunodeficiency Virus (HIV) Infection 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

4 week–11 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinica Somer ( Site 1003), Rionegro, Antioquia, Colombia

Loading trial locations.

About this study

Participants who complete the Week 96 visit will be eligible to enroll in an Extension Study and receive DOR until it is commercially available, or for up to an additional 224 weeks (whichever comes first).

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Has human immunodeficiency virus type 1 (HIV-1) infection confirmed at screening
  • Has appropriate treatment history defined as treatment-naïve (TN) or with documented virologic suppression (HIV-1 ribonucleic acid [RNA] <50 copies/mL) on stable combination antiretroviral therapy (cART) for ≥3 months
  • Body weight is >3 kg to <45 kg
  • If female, is not pregnant or breastfeeding, and one of the following applies:
  • Is not a woman of childbearing potential (WOCBP)
  • Is a WOCBP using an acceptable form of contraception, or is abstinent
  • If a WOCBP must have a negative pregnancy test (urine or serum) within 24 hours of the first dose of study intervention

Study Extension Inclusion Criteria:

  • Has completed the Week 96 visit
  • Is considered, in the opinion of the investigator, to have derived benefit from treatment with doravirine (DOR) plus the 2 nucleoside/nucleotide analog reverse transcriptase inhibitor (NRTIs) selected by the investigator, or doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), by Week 96 of the study
  • Is considered, in the opinion of the investigator, to be a clinically appropriate candidate for additional treatment with DOR regimens (DOR plus 2 NRTIs selected by the investigator or DOR/3TC/TDF)
  • Understands the procedures in the study extension and has provided (or have the participant's legally acceptable representative, if applicable, provide) documented informed consent/assent to enter the study extension and continue treatment with DOR regimens (DOR plus 2 NRTIs selected by the investigator or DOR/3TC/TDF) until it is available locally in countries participating in the study or for up to an additional 224 weeks (whichever comes first)

Exclusion criteria

  • Has evidence of renal disease
  • Demonstrates evidence of liver disease
  • Has clinical or laboratory evidence of pancreatitis
  • Has any history of malignancy
  • Has presence of any active acquired immunodeficiency syndrome (AIDS)-defining opportunistic Infection
  • Has an active diagnosis of hepatitis, including hepatitis B co-infection
  • Has current active tuberculosis and/or is being treated with a rifampicin-containing regimen
  • Has a medical condition that precludes absorption or intake of oral pellets/granules
  • Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study or interfere with participating for the entire duration of the study
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or other prohibited therapy
  • Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from 45 days prior to Day 1 through the treatment period
  • Has a documented or known virologic resistance to DOR
  • Has any history of viremia (HIV RNA >1000 copies/mL) after at least 3 months on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen

Treatment and study plan

Doravirine

Drug

Administered orally

Other names: MK-1439

2 NRTIs

Drug

Administered orally

DOR/3TC/TDF

Drug

Administered orally

Other names: MK-1439A

Primary outcomes

  1. Area Under the Concentration-Time Curve (AUC) From 0 to 24 Hours Postdose (AUC0-24hr) of Doravirine (DOR) Following Once-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive pharmacokinetic (PK) sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr.

  2. Maximum Concentration (Cmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax.

  3. Concentration at 24 Hours (C24) of DOR Following Once-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine C24.

  4. Time to Maximum Concentration (Tmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Tmax.

  5. AUC From 0 to 12 Hours Postdose (AUC0-12hr) of DOR Following Twice-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine AUC0-12hr.

  6. Cmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Cmax.

  7. Concentration at 12 Hours (C12) of DOR Following Twice-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine C12.

  8. Tmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Tmax.

  9. Percentage of Participants With ≥1 Adverse Event (AE)

    Time frame: Up to 24 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  10. Percentage of Participants With a Grade 3 or 4 AE

    Time frame: Up to 24 weeks

    Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated" (Grade 3), or "potentially life-threatening events" (Grade 4).

  11. Percentage of Participants With Events of Death

    Time frame: Up to 24 weeks

    The percentage of participants with events of death at Week 24 will be reported.

  12. Percentage of Participants Discontinuing From Study Intervention Due to an AE

    Time frame: Up to 24 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  13. Percentage of Participants Discontinuing From Study Intervention Due to a Drug-Related AE

    Time frame: Up to 24 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to the study interventions.

Secondary outcomes

  1. Plasma Concentration of DOR

    Time frame: Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks

    Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks.

  2. Plasma Concentration of Lamivudine (3TC) Following Once-Daily Dosing of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) as an Age-Appropriate Fixed-Dose Combination (FDC)

    Time frame: Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks

    Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks.

  3. Plasma Concentration of Tenofovir (TFV) Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

    Time frame: Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks

    Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks.

  4. AUC0-24hr of 3TC Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr of 3TC.

  5. AUC0-24hr of TFV Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr of TFV.

  6. Cmax of 3TC Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax of 3TC.

  7. Cmax of TFV Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

    Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

    Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax of TFV.

  8. Percentage of Participants With ≥1 AE at Week 48

    Time frame: Up to 48 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  9. Percentage of Participants With ≥1 AE at Week 96

    Time frame: Up to 96 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  10. Percentage of Participants With Grade 3 or 4 AE at Week 48

    Time frame: Up to 48 weeks

    Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated" (Grade 3), or "potentially life-threatening events" (Grade 4).

  11. Percentage of Participants With Grade 3 or 4 AE at Week 96

    Time frame: Up to 96 weeks

    Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated" (Grade 3), or "potentially life-threatening events" (Grade 4).

  12. Percentage of Participants With Events of Death at Week 48

    Time frame: Up to 48 weeks

    The percentage of participants with events of death at Week 48 will be reported.

  13. Percentage of Participants With Events of Death at Week 96

    Time frame: Up to 96 weeks

    The percentage of participants with events of death at Week 96 will be reported.

  14. Percentage of Participants Discontinuing From Study Intervention Due to AE at Week 48

    Time frame: Up to 48 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  15. Percentage of Participants Discontinuing from Study Intervention Due to AE at Week 96

    Time frame: Up to 96 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  16. Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 48

    Time frame: Up to 48 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to the study interventions.

  17. Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 96

    Time frame: Up to 96 weeks

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to the study interventions.

  18. Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL at Week 24

    Time frame: Up to 24 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL.

  19. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48

    Time frame: Up to 48 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  20. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96

    Time frame: Up to 96 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  21. Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 24

    Time frame: Up to 24 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  22. Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48

    Time frame: Up to 48 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  23. Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96

    Time frame: Up to 96 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  24. Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 24

    Time frame: Up to 24 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  25. Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48

    Time frame: Up to 48 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  26. Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96

    Time frame: Up to 96 weeks

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  27. Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 24

    Time frame: Baseline (Day 1) and Week 24

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  28. Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 48

    Time frame: Baseline (Day 1) and Week 48

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  29. Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 96

    Time frame: Baseline (Day 1) and Week 96

    Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.

  30. Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 24

    Time frame: Baseline (Day 1) and Week 24

    CD4+ T-cell counts will be performed at the central laboratory.

  31. Change From Baseline in CD4+ T-Cell Counts at Week 48

    Time frame: Baseline (Day 1) and Week 48

    CD4+ T-cell counts will be performed at the central laboratory.

  32. Change From Baseline in CD4+ T-Cell Counts at Week 96

    Time frame: Baseline (Day 1) and Week 96

    CD4+ T-cell counts will be performed at the central laboratory.

  33. Viral Resistance-Associated Substitutions (RASs) to DOR or Other Treatment Components

    Time frame: Up to 96 weeks

    The presence of viral RASs to DOR or other treatment components will be monitored for up to 96 weeks.

  34. Percentage of Participants Adhering to DOR or to the FDC of DOR/3TC/TDF

    Time frame: Up to 96 weeks

    Adherence to DOR or to the FDC of DOR/3TC/TDF will be monitored for up to 96 weeks.

  35. Assessment of Palatability/Acceptability of Oral Pellets/Granules of DOR or the FDC of DOR/3TC/TDF

    Time frame: Day 28

    Palatability/acceptability will be based on scores on the 5-point facial hedonic scale (FHS). FHS scores will be tabulated and summarized by mean and standard deviation (SD), on Day 28. The highest possible FHS score is 5, with higher scores indicative of greater palatability.

Study contacts

Contact information is provided by the study sponsor or research team.

Toll Free Number

CONTACT

[email protected]

1-888-577-8839

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Phase 2 Clinical Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Participants With HIV-1, Who Are 4 Weeks to Less Than 12 Years of Age and Weigh Less Than 45 kg

Important dates

Study start
2021
Primary completion
2028
Study completion
2034
First posted
May 5, 2020
Registry last updated
Jul 8, 2026

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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