E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the antiretroviral activity of islatravir (ISL) administered with different doses of MK-8507 once-weekly after switching from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) compared to continued treatment with BIC/FTC/TAF once-daily as assessed by the percentage of participants with human immunodeficiency virus type 1 ( HIV-1) ribonucleic acid (RNA) ≥50 copies/mL at Week 48 2. To evaluate the safety and tolerability of ISL + MK-8507 once weekly as assessed by review of the accumulated safety data |
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E.2.2 | Secondary objectives of the trial |
1. Antiretroviral (antiRTV) activity of switch to ISL + MK-8507 vs continued BIC/FTC/TAF treatment at Week 48 2. AntiRTV activity of switch to ISL + MK-8507 vs continued BIC/FTC/TAF treatment at Week 24 3. AntiRTV suppression of switch to ISL + MK-8507 vs continued BIC/FTC/TAF treatment at Week 96 4. Immunologic effect of switch to ISL + MK-8507 vs continued BIC/FTC/TAF treatment based on change from baseline in CD4+ T-cells Weeks 24, 48, and 96 5. AntiRTV suppression & immunologic effect of ISL + MK-8507 based on % with HIV-1 RNA ≥50 copies/mL & change from baseline in CD4+ T-cell count at Week 144 6. Development of viral drug resistance of switch to ISL + MK-8507 vs continued BIC/FTC/TAF treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening 2. Has a screening CD4+ T-cell count ≥200 cells/mm3 (completed by the central laboratory) 3. Has been receiving BIC/FTC/TAF therapy with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥6 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen 4. Is male or female, at least 18 years of age, at the time of signing the informed consent 5. 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 WOCBP OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), 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 - 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 - Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 6. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research |
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E.4 | Principal 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 active HCV coinfection (defined as detectable HCV RNA) or HBV coinfection (defined as HBsAg-positive or HBV DNA positive) (completed by the central laboratory) 4. Has a current (active) diagnosis of acute hepatitis due to any cause 5. 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 6. 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 7. 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 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 treatment period 9. Has a documented or known virologic resistance to: - any of the following MK-8507 or NNRTI resistance-associated substitutions in reverse transcriptase: L100I, K101E, K101P, K103N, K103S, V106A, V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179L, Y181C, Y181I, Y181V, Y188C, Y188H, Y188L, G190A, G190E, G190S, H221Y, P225H, F227C, F227L, F227V, M230I, M230L, L234I, Y318F - any of the following NRTI resistance-associated substitutions in reverse transcriptase: M184I, M184V 10. Has exclusionary laboratory values (completed by the central laboratory) within 45 days prior to Day 1 11. Is female and expecting to conceive or donate eggs at any time during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Percentage of participants with HIV-1 RNA ≥50 copies/mL 2. Percentage of participants with ≥1 adverse event (AE) 3. Percentage of participants discontinuing study intervention due to AE |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Week 48 2. Up to 96 weeks 3. Up to 96 weeks |
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E.5.2 | 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 ≥50 copies/mL 4. Percentage of participants with HIV-1 RNA <50 copies/mL 5. Percentage of participants with HIV-1 RNA <40 copies/mL 6. Percentage of participants with HIV-1 RNA ≥50 copies/mL 7. Percentage of participants with HIV-1 RNA <50 copies/mL 8. Percentage of participants with HIV-1 RNA <40 copies/mL 9. Change from BL in CD4+ T-cell count 10. Change from BL in CD4+ T-cell count 11. Change from BL in CD4+ T-cell count 12. Percentage of participants with HIV-1 RNA ≥50 copies/mL 13. Change from BL in CD4+ T-cell count 14. Incidence of viral drug resistance |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 48 2. Week 48 3. Week 24 4. Week 24 5. Week 24 6. Week 96 7. Week 96 8. Week 96 9. Baseline (Day 1) and Week 24 10. Baseline (Day 1) and Week 48 11. Baseline (Day 1) and Week 96 12. Week 144 13. Baseline (Day 1) and Week 144 14. Up to 144 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open in Part 2 and Part 3 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |