HIV-1 infection and naïve to antiretroviral therapy MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is HIV-1 positive with plasma HIV-1 RNA =500 copies/mL at screening. 2. Is naïve to ART defined as having received =10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening. 3. Is male or female =18 years of age inclusive at the time of signing informed consent. 4. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) OR - Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 5 during the intervention period and for at least 6 weeks, corresponding to the time needed to eliminate any study intervention(s) (eg, 5 terminal half-lives) after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie,noncompliance, recently initiated) in relationship to the first dose of study intervention. - A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention. - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are located in the protocol. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 5. The participant provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 669 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: 1. Has HIV-2 infection. 2. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. 3. Has an active diagnosis of hepatitis due to any cause, including active HBV infection (defined as HBsAg-positive or HBV DNA positive). 4. 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. 5. 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. 6. Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1, including, but not limited to, the following: adefovir, TDF,TAF, FTC, or 3TC. 7. Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any of the prohibited therapies outlined in Section 6.5 from 45 days prior to Day 1 through the study intervention period. 8. Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study intervention period. 9. Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention, as demonstrated by any of the following resistance substitutions (according to the 2017 IAS-USA drug resistance mutations list) [Wensing, A. M., et al 2017]: a. FTC: K65R/E/N or M184I/V b. TAF: K65R/E/N or K70E c. Multi-NRTI resistance substitutions: T69insert, Q151M, or 3 or more of thymidine analogue-associated mutations (M41L, D67N, K70R, L210W, T215F/Y, K219E/Q). d. DOR resistance substitutions: V106A/M, V108I, Y188L, H221Y, P225H, F227C/L, M230I/L, L234I, P236L, or Y318F. 10. Has exclusionary laboratory values (completed by the central laboratory) within 45 days prior to Day 1 11. Is female and is expecting to conceive or donate eggs at any time during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the antiretroviral activity of doravirine/islatravir (DOR/ISL) compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48 2. To evaluate the safety and tolerability of DOR/ISL compared to BIC/FTC/TAF as assessed by review of the accumulated safety data through Weeks 48 and 96 ;Secondary Objective: 1. To evaluate the antiretroviral activity of DOR/ISL compared to BIC/FTC/TAF based on the percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 2. To evaluate the antiretroviral activity of DOR/ISL compared to BIC/FTC/TAF based on the percentage of participants with HIV-1 RNA <40 and <200 copies/mL at Week 48 3. To evaluate the antiretroviral activity of DOR/ISL compared to BIC/FTC/TAF as assessed by the percentage of participants with HIV-1 RNA <40 and <200 copies/mL at Week 96 4. To evaluate the immunologic effect of DOR/ISL as measured by the change from baseline in cluster of differentiation 4+ (CD4+) T-cell count at Weeks 48 and 96 5. To evaluate the development of viral drug resistance in participants who receive DOR/ISL and in those who receive BIC/FTC/TAF 6. To evaluate the effect of DOR/ISL compared to BIC/FTC/TAF on weight, as measured by the mean change from baseline to Weeks 48 and 96 ;Primary end point(s): 1. Percentage of participants with HIV-1 RNA <50 copies/mL 2. Percentage of participants experiencing =1 adverse events (AEs) 3. Percentage of participants discontinuing from study treatment due to AE(s) ;Timepoint(s) of evaluation of this end point: 1. Week 48 2. Up to 98 weeks 3. Up to 96 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of participants with HIV-1 RNA <50 copies/mL 2. Percentage of participants with HIV-1 RNA <40 copies/mL 3. Percentage of participants with HIV-1 RNA <200 copies/mL 4. Percentage of participants with HIV-1 RNA <40 copies/mL 5. Percentage of participants with HIV-1 RNA <200 copies/mL 6. Change from baseline in CD4+ T-cell counts 7. Change from baseline in CD4+ T-cell counts 8. Incidence of viral resistance-associated substitutions (RASs) 9. Incidence of viral resistance-associated substitutions (RASs) 10. Change from baseline in body weight 11. Change from baseline in body weight ;Timepoint(s) of evaluation of this end point: 1. Week 96 2. Week 48 3. Week 48 4. Week 96 5. Week 96 6. Week 48 7. Week 96 8. Up to 48 weeks 9. Up to 96 weeks 10. Week 48 11. Week 96 | — |
Countries
Argentina, Canada, Chile, Colombia, France, Germany, Israel, Italy, Japan, South Africa, Spain, Taiwan, United States
Contacts
Public ContactElizabeth Martin
Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc
Outcome results
None listed