A Phase 3. Randomized. Active-Controlled. Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 Infected® Treatment-Naive Participants
Hypotheses, Objectives, and Endpoints:
Hypotheses are aligned with objectives in the Objectives and Endpoints table.
The following objectives will be evaluated in participants ≥18 years of age who are infected with ElV-1 and naïve to antiretroviral therapy.
| Total Number of Intervention Groups/Arms | 1 |
| I0 evaluate the antiretrovual acuvitv of DOR/ISL compared to BIC/FIC/TAf assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 Hypothesis (H1): DOR/ISL is non-inferior to BIC/FTC/TAF, as assessed by thc percentage of participants with HIV I RNA < 50 copies/mL at Week 48. A margin of 10 percentage points is used to define non- inferiority |
HIV-1 RNA |
| To evaluate the safety and tolerability of DO/ISL compared with BIC/FTC/TAF as assessed by review of the accumulated safety data through Week 48 |
Adverse events Adverse events leading to discontinuation of study intervention |
| Secondary Objectives | Secondary Endpoints |
|---|---|
| To evaluate the antiretroviral activity of DO/ISL compared with BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 |
HIV-1 RNA |
| To evaluate the antiretroviral activity of DOR/ISL compared with BIC/FTC/TAF as assessed by the percentage of participants with FIV-RNA <200 copies/mL at Week 48 and Week 96 |
HIV-IRNA |
| To evaluate the immunologic eftect ol DOR ISL compared with BIGFIC/Ar. as assessed by the mean change from baseline in CD4+ T-cell count at Week 48 and Week 96 |
CD4+ T-cell count |
| To evaluate the development of Viral drug resistance in participants who receive DOR/ISL and in those who recerve BIC/FTC/TAF |
Viral resistance-associated substitutions |
| To evaluate the effect of DORIST. compared with BIC/FICTAf on weight, as assessed by the mean change from baselin to Weck 48 and Week 96To evaluate the effect of DORIST. compared with BIC/FICTAf on weight, as assessed lower mean increase from from baselin to Weck 48 and Week 96Hypothesis (H3): DO/ISL is superior to BIC/ETC/TAF as assessed by lower mean increase from baseline in weight at Week 96 |
Weight |
| To evaluate the safety and tolerability of DOK/ISL compared with BIC/FICTAF as assessed by review of the accumulated safety data through study duration |
Adverse events Adverse events leading to discontinuation of study intervention |
| Study Phase | Phase 3 |
| Primary Purpose | Treatment |
| Indication | HIV infection |
| Population | Participants ≥18 years of age with HIV-1 who are naive to antiretroviral therapy |
| Study Type | Interventional |
| Intervention Model | Parallel This is a multi site study. |
| Type of Control | Active Control |
| Study Blinding | Double-blind |
| Blinding Roles | Participants or Subjects Sponsor Investigator |
| Estimated Duration of Study | The Sponsor estimates that the study will require approximately 3.0 years from the time the first participant (or their legally acceptable representative) provides documented informed consent until the last participant’s last study-related contact. |
Number of Participants: Approximately 500 participants will be randomized.
Intervention Groups and Duration:
| Arm Name | intervention Name | Unit Dose Strength(s) | Dosage Level(s) | Route of administration | Regimen/Treatment Period | Use |
|---|---|---|---|---|---|---|
| Group 1 | doravirin/islatravir | 100 mg/ 0.25 mg | 100 mg 0.25 mg QD | Oral | Day 1 to Week 96 | Test Product |
| Group 1 | Placebo to bictegravir/ emtricitabine/ tenofovir alafenamide |
10 mg | 0 mg QD | Oral | Day 1 to Week 96 | Placebo |
| Group 2 | bictegravir/ emtricitabine/ tenofovir alafenamide |
50 mg/ 200 mg/ 25 mg QD |
50 mg/ 200 mg/ 25 mg QD |
Oral | Day 1 to Week 96 | Comparator |
| Group 2 | Placebo to doravirine/ islatravir |
0 mg | 0 mg QD | Oral | Day 1 to Week 96 | Placebo |
QD once daily
Study intervention will be extended open-label for participants who become pregnant on treatment and provide documented informed consent to continue study intervention
(DOR/ISL or BIC/FTC/TAF) as specified in Sections 1.3.4 and 8.11.6.
| Total Number of Intervention Groups/Arms | 2 |
| Duration of Participation | Each participant will participate in the study for approximately 2 years from the time the participant provides documented informed consent through the final contact. After a screening phase of up to 45 days, each participant will receive the assigned blinded study intervention for approximately 96 weeks. Participants who discontinue study intervention or who become pregnant will be followed up as described in the protocol. |
| Executive Oversight Committee | Yes |
| Data Monitoring Committee | Yes |
| Clinical Adjudication Committee | No |
Study governance considerations are outlined in Appendix 1.
Study Accepts Healthy Participants: No
A list of abbreviations is in Appendix 9.
