Doravirine/Islatravir (DOR/ISL) in Pediatric Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are <18 Years of Age and Weigh ≥35 kg (MK-8591A-028)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04295772 |
Recruitment Status :
Recruiting
First Posted : March 4, 2020
Last Update Posted : February 15, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
HIV-1 Infection | Drug: DOR/ISL | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 45 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2 Clinical Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Doravirine/Islatravir in Pediatric Participants With HIV-1 Infection Who Are Virologically Suppressed or Treatment-Naïve, Are Less Than 18 Years of Age, and Weigh Greater Than or Equal to 35 kg |
Actual Study Start Date : | November 26, 2020 |
Estimated Primary Completion Date : | July 29, 2022 |
Estimated Study Completion Date : | January 26, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: DOR/ISL
Pediatric participants with HIV-1 infection receive DOR/ISL for 96 weeks.
|
Drug: DOR/ISL
100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.
Other Names:
|
- Area under the plasma drug concentration-time curve from 0 to 24 hours post-dose (AUC0-24) of islatravir (ISL) [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28 ]The AUC0-24 of ISL in plasma will be determined at steady state.
- Maximum plasma concentration (Cmax) of ISL [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28 ]The Cmax of ISL in plasma will be determined at steady state.
- Time to reach maximum plasma concentration (Tmax) of ISL [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28 ]The Tmax of ISL in plasma will be determined at steady state.
- Apparent total clearance from plasma (CL/F) of ISL [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28 ]The CL/F of ISL from plasma will be determined at steady state.
- Apparent volume of distribution during terminal phase (Vz/F) of ISL [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28 ]The Vz/F of ISL will be determined at steady state.
- Apparent plasma terminal half-life (t½) of ISL [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28 ]The t½ of ISL in plasma will be determined at steady state.
- AUC0-24 of ISL-triphosphate (ISL-TP) in PBMCs [ Time Frame: Pre-dose, and 4 and 24 hours post-dose on Day 28 ]The AUC0-24 of ISL-TP in PBMCs will be determined at steady state.
- Cmax of ISL-TP in PMBCs [ Time Frame: Pre-dose, and 4, and 24 hours post-dose on Day 28 ]The Cmax of ISL-TP in PBMCs will be determined at steady state.
- C24 of ISL-TP in PBMCs [ Time Frame: 24 hours post-dose on Day 28 ]The C24 of ISL-TP in PBMCs will be determined at steady state.
- Percentage of participants experiencing ≥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 intervention.
- Percentage of participants discontinuing from study treatment 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 intervention.
- Percentage of participants experiencing ≥1 adverse event (AE) [ Time Frame: Up to at least 48 weeks (through study duration) ]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 intervention.
- Percentage of participants discontinuing from study treatment due to an AE [ Time Frame: Up to at least 48 weeks (through study duration) ]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 intervention.
- Percentage of VS participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL [ Time Frame: Week 24 ]The percentage of VS participants with HIV-1 RNA ≥50 copies/mL will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.
- Percentage of VS participants with HIV-1 RNA ≥50 copies/mL [ Time Frame: Week 48 ]The percentage of VS participants with HIV-1 RNA ≥50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of VS participants with HIV-1 RNA ≥50 copies/mL [ Time Frame: Week 96 ]The percentage of VS participants with HIV-1 RNA ≥50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of VS participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 24 ]The percentage of VS participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of VS participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 48 ]The percentage of VS participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of VS participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 96 ]The percentage of VS participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of TN participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 24 ]The percentage of TN participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of TN participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 48 ]The percentage of TN participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of TN participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 96 ]The percentage of TN participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cells in VS participants [ Time Frame: Baseline (Day 1) and Week 24 ]CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in CD4+ T-cells in VS participants [ Time Frame: Baseline (Day 1) and Week 48 ]CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in CD4+ T-cells in VS participants [ Time Frame: Baseline (Day 1) and Week 96 ]CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in CD4+ T-cells in TN participants [ Time Frame: Baseline (Day 1) and Week 24 ]CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in CD4+ T-cells in TN participants [ Time Frame: Baseline (Day 1) and Week 48 ]CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in CD4+ T-cells in TN participants [ Time Frame: Baseline (Day 1) and Week 96 ]CD4+ T-cell counts will be measured by a central laboratory.
- Incidence of viral drug resistance to DOR [ Time Frame: Up to at least 48 weeks (through study duration) ]The incidence of viral drug resistance to DOR will be determined.
- Incidence of viral drug resistance to ISL [ Time Frame: Up to at least 48 weeks (through study duration) ]The incidence of viral drug resistance to ISL will be determined.
- Mean score on a 5-point visual analog facial hedonic scale assessing ease or difficulty associated with swallowing the DOR/ISL tablet [ Time Frame: Day 1 and Day 28 ]The palatability and acceptability of the DOR/ISL tablet will be measured by a 5-point facial hedonic scale depicting various degrees of pleasure/displeasure that was modified from a Wong-Baker scale. Scores range from 1 ("worst swallowability/most discomfort") to 5 ("easiest swallowability/no discomfort at all"). Scores will be determined on Days 1 and 28.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | up to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Is HIV-1 positive, is <18 years of age, and weighs ≥35 kg at screening.
- VS Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA <50 copies/mL and has been receiving continuous, stable oral 2-drug or 3-drug combination ART ± PK booster with documented viral suppression for ≥3 months prior to signing informed consent/assent
- TN Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA ≥500 copies/mL and is naive to ART defined as having received <=10 days of prior therapy with any antiretrovirals following HIV-1 diagnosis other than pre-exposure prophylaxis (PrEP) or potentially exposed person (PEP)
- If female, is not pregnant or breastfeeding, and is either 1) not a woman of childbearing potential (WOCBP) or 2) is a WOCBP and is using acceptable contraception or is abstinent.
Exclusion Criteria:
- Has HIV-2 infection.
- Has hypersensitivity or other contraindication to any of the components of the study drugs as determined by the investigator.
- Has an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive).
- Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma.
- Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate.
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 45 days prior to Day 1 through the study treatment period.
- Is currently taking long-acting cabotegravir-rilpivirine.
- 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 study treatment period.
- Has a documented or known virologic resistance to DOR.
- Has exclusionary laboratory values.
- Is female and expecting to conceive or donate eggs at any time during the study.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04295772
Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
United States, Maryland | |
Johns Hopkins University ( Site 1800) | Recruiting |
Baltimore, Maryland, United States, 21287 | |
Contact: Study Coordinator 410-614-3917 | |
United States, North Carolina | |
Duke University ( Site 1807) | Recruiting |
Durham, North Carolina, United States, 27710 | |
Contact: Study Coordinator 919-360-9199 | |
Italy | |
Azienda Ospedaliera Luigi Sacco ( Site 1300) | Recruiting |
Milano, Italy, 20157 | |
Contact: Study Coordinator +393485847837 | |
IRCCS Ospedale Pediatrico Bambino Gesu ( Site 1301) | Recruiting |
Roma, Italy, 00165 | |
Contact: Study Coordinator +390668592190 | |
Russian Federation | |
Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 1507) | Recruiting |
Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660049 | |
Contact: Study Coordinator +79029431209 | |
Infectious Clinical Hospital #2 ( Site 1501) | Recruiting |
Moscow, Moskva, Russian Federation, 105275 | |
Contact: Study Coordinator +79037143865 | |
FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1500) | Recruiting |
Saint Petersburg, Sankt-Peterburg, Russian Federation, 196645 | |
Contact: Study Coordinator +78124649329 | |
Saratov Regional Center for Prophylaxis and Control of AIDS ( Site 1505) | Recruiting |
Saratov, Saratovskaya Oblast, Russian Federation, 410009 | |
Contact: Study Coordinator +78452201809 | |
Thailand | |
Chulalongkorn University ( Site 1602) | Recruiting |
Bangkok, Krung Thep Maha Nakhon, Thailand, 10330 | |
Contact: Study Coordinator +6622564930 | |
Siriraj Hospital ( Site 1601) | Recruiting |
Bangkok, Krung Thep Maha Nakhon, Thailand, 10700 | |
Contact: Study Coordinator +6624180545 |
Study Director: | Medical Director | Merck Sharp & Dohme Corp. |
Responsible Party: | Merck Sharp & Dohme Corp. |
ClinicalTrials.gov Identifier: | NCT04295772 |
Other Study ID Numbers: |
8591A-028 2019-003597-10 ( EudraCT Number ) MK-8591A-028 ( Other Identifier: Merck Protocol Number ) |
First Posted: | March 4, 2020 Key Record Dates |
Last Update Posted: | February 15, 2021 |
Last Verified: | February 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
URL: | http://engagezone.msd.com/ds_documentation.php |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Infection 4'-ethynyl-2-fluoro-2'-deoxyadenosine Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |