E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of HIV-1 Infection |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of HIV-1 Infection |
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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 |
To evaluate the vaccine efficacy (VE) of a heterologous vaccine regimen utilizing Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140 and Mosaic gp140 for the prevention of HIV-1 infection in HIV-1 seronegative cis-gender men and transgender individuals having sex with cis-gender men and/or transgender individuals. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety and reactogenicity of a heterologous vaccine regimen utilizing Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140 and Mosaic gp140 for the prevention of HIV-1 infection in HIV-1 seronegative cis-gender men and transgender individuals having sex with cis-gender men and/or transgender individuals. 2. To evaluate VE at other timepoints and in other analysis populations. 3. To evaluate VE by and adjusting for potential (baseline) confounders. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Potential participant is ≥18 to ≤60 years old on the day of signing the ICF.
● Individual is either: - Cis-gender man having sex with cis-gender men and/or transgender individuals, OR - Transgender woman having sex with cis-gender men and/or transgender individuals, OR - Transgender man having sex with cis-gender men and/or transgender women (transgender man having sex exclusively with transgender men is excluded), OR - Gender non-conforming individual having receptive or insertive anal and/or vaginal condomless intercourse, AND who is considered by the site staff to be at increased risk for HIV-1 infection. The potential participants must in the last 6 months have had: - Any condomless receptive anal or vaginal sex (not included is condomless anal sex within a mutually monogamous relationship ≥12 months if the partner is HIV negative or living with HIV and virally suppressed), OR - Rectal or urethral gonorrhea or chlamydia or incident syphilis, OR - Any stimulant use (eg, cocaine, amphetamine), OR - 5 or more sex partners
● Potential participant is negative for HIV-1 and HIV-2 infection <28 days prior to first vaccination.
● Potential participant must be healthy based on medical history, physical examination, and vital sign measurement performed at screening.
● Contraceptive use by participants assigned female at birth and who have not had sexual reassignment surgery should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies.
● All participants of childbearing potential must: - Have a negative highly sensitive urine or serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening - Have a negative urine β-hCG pregnancy test immediately prior to each study vaccine administration |
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E.4 | Principal exclusion criteria |
● Potential participant shares needles during injection of drugs or any other substance.
● Potential participant has any clinically significant acute or chronic medical condition that in the opinion of the investigator would preclude participation.
● Potential participant received or plans to receive: - licensed live attenuated vaccines - within 28 days before or after planned administration of the first or subsequent study vaccination[s] - other licensed (not live) vaccines - within 14 days before or after planned administration of the first or subsequent study vaccination[s].
● Potential participants choosing to use PrEP. However, once participants are enrolled and received their first vaccination, and they change their mind regarding PrEP usage, they will be allowed to take PrEP according to the site PrEP plan and will continue to receive further vaccinations. ● Potential participant has used investigational research agents within 28 days of randomization.
● Potential participant is a recipient of a HIV-vaccine candidate at any time, or a recipient of other experimental vaccine(s) within the last 12 months prior to Day 1. For participants who received an experimental vaccine (except HIV vaccine) more than 12 months prior to Day 1, documentation of the identity of the experimental vaccine must be provided to the HPX3002/HVTN 706 safety review team, who will determine eligibility on a case-by-case basis.
● Potential participant has received an HIV-related mAb, whether licensed or investigational, within the last 12 months prior to Day 1. For participants who received an HIV-related mAb more than 12 months prior to Day 1, documentation of the identity of the mAb must be provided to the HPX3002/HVTN 706 safety review team, who will determine eligibility on a case-by-case basis.
● Potential participant has been in receipt of blood or Ig products in the past 3 months.
● Potential participant has known allergy or history of anaphylaxis or other serious adverse reactions to vaccines.
● Potential participant has a history of any chronic/recurrent conditions that require regular/recurrent use of oral/parenteral corticosteroids or other immunomodulators/immunosuppressors. Ocular, topical or inhaled steroids are allowed.
● Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study vaccination. History of TTS or HITT |
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E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed HIV-1 infections diagnosed between Month 7 and Month x (with 24≤x≤30) visits in the per-protocol (PP) population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. a) Reactogenicity: Solicited administration site and systemic adverse events for 7 days after each vaccination b) Unsolicited adverse events for 28 days after each vaccination c) Medically-attended adverse events (MAAEs) for the entire duration of the study d) Serious adverse events for the entire duration of the study e) Discontinuations from the study or vaccination due to adverse events
2. Confirmed HIV-1 infections over different time intervals (eg, VE[0-x months], VE[13-x months]) and in different populations (eg, modified intent-to-treat [mITT], mITT-2, full immunization set [FIS])
3. Potential confounders include but are not limited to: demographic characteristics, baseline Ad26 seropositivity status and titer, sexual risk behavior, and pre-exposure prophylaxis (PrEP) use. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. a) 7 days after each vaccination b) 28 days after each vaccination c), d) & e) Throughout the duration of the study
2. Months 0, 3, 6, 7, 9, 12, 13, 15, 18, 21, 24, 27 and 30, every 3 months post Month 30 follow-up visit and exit visit
3. Throughout the duration of the study |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Reactogenicity, Immunogenicity, Patient reported outcomes |
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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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Argentina |
Peru |
Brazil |
Italy |
Mexico |
Poland |
Spain |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 25 |