| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 10021881 - Infections and infestations |
|
| 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 following switch to Doravirine/Islatravir (DOR/ISL) compared to continued treatment with Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) as
assessed by the percentage of participants with Human Immunodeficiency Virus 1 (HIV-1) RNA ≥50 copies/mL at Week 48
2.To evaluate the safety and tolerability of switch to DOR/ISL compared
to continued treatment with BIC/FTC/TAF as assessed by review of the accumulated safety data through Week 48 |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the antiretroviral activity as assessed by the percentage of participants with HIV-1 RNA >50 copies/mL at Week 96
2. To evaluate the antiretroviral activity as assessed by the percentage of participants with HIV-1 RNA >50 copies/mL at Week 144
3. To evaluate the antiretroviral activity as assessed by the percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 48
4. To evaluate the antiretroviral activity as assessed by the percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 96
5. To evaluate the antiretroviral activity as assessed by the percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 144
6. To evaluate the immunologic effect as measured by change from baseline in CD4+ T-cell count at Weeks 48, 96 and 144
7. To evaluate the development of viral drug resistance
8. To evaluate the effect on body weight to Weeks 48, 96 and 144
9. To evaluate the safety and tolerability through Week 144 |
|
| 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 been receiving BIC/FTC/TAF therapy with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen
3.Is male or female, at least 18 years of age at the time of signing the 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), 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
5.The participant (or legally acceptable representative) has provided documented 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 |
|
| 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 an active diagnosis of hepatitis due to any cause, including active HBV coinfection (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.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
7.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
8.Has a documented or known virologic resistance to DOR, as demonstrated by any of the following DOR resistance substitutions in reverse transcriptase: V106A/M, V108I, Y188L, H221Y, P225H, F227C/L, M230I/L, L234I, P236L, or Y318F
9.Has exclusionary laboratory values (completed by the central laboratory) within 45 days prior to Day 1
10.Is female and expecting to conceive or donate eggs at any time during the study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1.Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
2.Percentage of participants with one or more adverse events (AEs) up to Week 48
3.Percentage of participants who discontinued study intervention due to an AE up to Week 48 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Week 48
2. Week 48
3. Week 48 |
|
| E.5.2 | Secondary end point(s) |
1. Percentage of participants with HIV-1 RNA >50 copies/mL at Week 96
2. Percentage of participants with HIV-1 RNA >50 copies/mL at Week 144
3. Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 48
4. Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 96
5. Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 144
6. Change from baseline in CD4+ T-cell count at Week 48
7. Change from baseline in CD4+ T-cell count at Week 96
8. Change from baseline in CD4+ T-cell count at Week 144
9.Percentage of participants with viral drug resistance-associated substitutions at Week 48
10. Percentage of participants with viral drug resistance-associated substitutions at Week 96
11. Percentage of participants with viral drug resistance-associated substitutions at Week 144
12. Change from baseline in body weight at Week 48
13. Change from baseline in body weight at Week 96
14. Change from baseline in body weight at Week 144
15. Percentage of participants with one or more AEs up to Week 144
16. Percentage of participants who discontinued study intervention due to an AE up to Week 144 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 96
2. Week 144
3. Week 48
4. Week 96
5. Week 144
6. Baseline and Week 48
7. Baseline and Week 96
8. Baseline and Week 144
9. Week 48
10. Week 96
11. Week 144
12. Baseline and Week 48
13. Baseline and Week 96
14. Baseline and Week 144
15. Week 144
16. Week 144 |
|
| 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 | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 |
| Eligible participants will be given the option to continue treatment with DOR/ISL as open label |
|
| 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 | 2 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 39 |
| 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 |
| Puerto Rico |
| Australia |
| Canada |
| Japan |
| United States |
| Austria |
| Finland |
| France |
| Germany |
| Italy |
| Spain |
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
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