A Phase I Study of an HIV Vaccine in Healthy, HIV Uninfected Adults

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of Modified Vaccinia Ankara (MVA) Mosaic vaccine in healthy adult participants.

Detailed Description
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This is a Phase I, placebo-controlled (the use of an inactive substance identical in appearance to the active vaccine), double-blind (neither the participant or study personnel will know the identity of the treatment administered) study where participants will be randomized (treatment type assigned by chance) to receive a Modified Vaccinia Ankara (MVA) Mosaic vaccine (at 1x10E8 pfu) or placebo. This design is intended to reduce the likelihood of observer and selection bias, provide control for confounding variables, and aid an unbiased analysis of the study results. The study will include 4 groups of participants, 2 groups having previously been vaccinated with Ad26.ENVA.01 (A recombinant adenovirus [rAd] vaccine for HIV-1) and 2 groups not previously vaccinated with Ad26.ENVA.01. Participants will be randomized in a 4:1 ratio to receive either a MVA Mosaic vaccine or placebo. The trial comprises a 4-week screening period, a 12-week vaccination period during which participants will be vaccinated at baseline (Day 1) and Week 12 (Day 84), and a 40-week follow-up period to the final visit at Week 52.

Official Title
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A Phase I Study of Modified Vaccinia Ankara With Mosaic HIV Inserts in Healthy, HIV-Uninfected Adults, Some of Whom Have Previously Received an Adenovirus Type 26 ENVA.01 Vaccine

Conditions
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Healthy

Intervention / Treatment
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* Biological: MVA Mosaic
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults (determined by medical history, physical examination, and clinical judgment) HIV uninfected Female participants of child bearing potential must have a negative serum β-human chorionic gonadotrophin pregnancy test at the screening visit and immediately prior to each vaccine/placebo administration, practice adequate birth control measures from 28 days prior to the first vaccine/placebo administration through to at least 3 months after the final vaccine/placebo administration Male participants who are sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a double barrier method of birth control, e.g. either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository Exclusion Criteria: Confirmed HIV-1/-2 infection Chronic active hepatitis B or hepatitis C or active syphilis infection. Active syphilis documented by exam or serology unless positive serology is due to past treated infection Within the 12 months prior to enrollment: a history of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranulomavenereum, chancroid, or hepatitis B A woman who is breastfeeding Any clinically significant acute or chronic medical condition that, in the opinion of the investigator, would preclude participation Major surgery within the 4 weeks prior to study entry or planned major surgery through the course of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1- MVA Mosaic<br>Healthy volunteers not previously vaccinated with Ad26.ENVA.01 will be administered Modified Vaccinia Ankara (MVA) Mosaic at Week 0 and at Week 12. | Biological: MVA Mosaic<br>* 0.5 mL (1x10E8 pfu) MVA Mosaic (comprised of MVA Mosaic 1 and MVA Mosaic 2 mixed in a 1:1 ratio before administration) will be administered by intramuscular (IM) injection.<br>|
| Placebo Comparator: Group 2 - Placebo<br>Healthy volunteers not previously vaccinated with Ad26.ENVA.01 will be administered placebo at Week 0 and at Week 12. | Biological: Placebo<br>* 0.5 mL Sodium Chloride Injection USP, 0.9%will be administered by intramuscular (IM) injection.<br>|
| Experimental: Group 3 - MVA Mosaic<br>Healthy volunteers previously vaccinated with Ad26.ENVA.01 will be administered MVA Mosaic at Week 0 and at Week 12. | Biological: MVA Mosaic<br>* 0.5 mL (1x10E8 pfu) MVA Mosaic (comprised of MVA Mosaic 1 and MVA Mosaic 2 mixed in a 1:1 ratio before administration) will be administered by intramuscular (IM) injection.<br>|
| Placebo Comparator: Group 4- Placebo<br>Participants previously vaccinated with Ad26.ENVA.01 will be administered placebo at Week 0 and at Week 12. | Biological: Placebo<br>* 0.5 mL Sodium Chloride Injection USP, 0.9%will be administered by intramuscular (IM) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants who Experience Adverse Events Within 28 days After Vaccination | In addition to the number of participants who experience adverse events within the time frame of 28 days after each vaccination, all adverse events that occur from the signing of the informed consent through to the last study visit (Visit 10 [Day 365]) will be reported. | For 28 days following vaccination on Day 1 and Day 84 | 
| The Number of Participants who Experience Reactogenicity Symptoms Following Vaccination | Reactogenicity symptoms monitored following vaccination will include erythema (redness), induration (hardening), and local pain/tenderness, itching, swelling, or warmth at the site of injection, temperature (fever >37.7 degree Celsius); fatigue (extreme tiredness), headache, myalgia (muscle pain), arthralgia (joint pain), chills, nausea, vomiting, rashes, and itching (general and local) | 1 week following vaccination on Day 1 and Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Humoral Immune Responses | Humoral immune responses will be evaluated by the detection of env-specific binding antibody. | 4 weeks after the second vaccination | 
| Durability of Immune Response | Determined by humoral immune response assays. | 6, 9, and 12 months after the first vaccination | 
| The Number of Participants With T-cell Responses Following Vaccination | T-cell responses to be determined by epitope mapping. | 4 weeks after the second vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Human immunodeficiency virus type 1 (HIV-1) infection, Acquired immunodeficiency syndrome (AIDS), recombinant adenovirus (rAd) vector-based vaccines, Vaccination, Ad26.ENVA.01, Recombinant, Modified Vaccinia Ankara (MVA) vector-based vaccines