A Safety, Tolerability and Immunogenicity Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With Tetravalent Ad26.Mos4.HIV Along With Either Clade C gp140 Plus Adjuvant OR With a Combination of Mosaic and Clade C gp140 Plus Adjuvant in Healthy HIV Uninfected Adults

Study Overview
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Brief Summary
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The primary purpose of this study is to assess safety/tolerability of the different vaccine regimens and of a late boost vaccination; and to assess envelope (Env)-binding antibody (Ab) responses of the 2 different vaccine regimens.

Detailed Description
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This is a randomized (study medication assigned by chance), double-blind (neither physician nor participant knows the treatment received), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each treatment group will be treated at the same time), multicenter (more than one clinical site) study in healthy human immunodeficiency virus (HIV)-uninfected adults. The main study will be conducted in 3 phases: a 6-week screening period; a 48-week vaccination period; and a follow-up period to the final main study visit at Week 72. A Long-term Extension (LTE) phase (approximately 3 years after Week 72) will be performed for participants randomized to Group 1 or Group 2, who receive all 4 vaccinations and are negative for HIV infection at Week 72. The approximate duration of the study will be approximately 78 weeks for participants not participating in the LTE phase and approximately 222 weeks for participants participating in the LTE phase but not receiving a late boost vaccination and approximately 246 (12-month follow-up) or 294 (24-month follow-up) weeks for participants receiving a late boost vaccination. Participants safety will be monitored throughout the study.

Official Title
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A Randomized, Parallel-group, Placebo-controlled, Double-blind Phase 1/2a Study in Healthy HIV Uninfected Adults to Assess Safety/Tolerability and Immunogenicity of 2 Different Prime/Boost Regimens: Priming With Tetravalent Ad26.Mos4.HIV and Boosting With Tetravalent Ad26.Mos4.HIV and Either Clade C gp140 Plus Adjuvant OR a Combination of Mosaic and Clade C gp140 Plus Adjuvant

Conditions
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Healthy

Intervention / Treatment
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* Biological: Ad26.Mos4.HIV
* Biological: Clade C gp140 plus adjuvant
* Biological: Clade C gp140/Mosaic gp140 plus adjuvant
* Other: Placebo
* Biological: gp140 HIV Bivalent Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be healthy on the basis of medical history, physical examination, and vital signs measurement performed at screening Participants are negative for human immunodeficiency virus (HIV) infection at screening Participants are amenable to HIV-risk reduction counseling and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit All female participants of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) at the screening visit, and a negative urine pregnancy test pre-dose on Day 1 Participants are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures Participant must be enrolled in the LTE phase to receive the late boost vaccination Exclusion Criteria: Has chronic hepatitis B (measured by hepatitis B surface antigen test) or active hepatitis C (measured by hepatitis C virus [HCV] Ab test; if positive, HCV ribonucleic acid [RNA] polymerase chain reaction (PCR) test will be used to confirm active versus past HCV infection), active syphilis infection, chlamydia, gonorrhea, or trichomonas In the 12 months prior to randomization, participant has a history of newly acquired herpes simplex virus type 2 (HSV-2), syphilis, gonorrhea, non-gonococcal urethritis, chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranulomavenereum, chancroid, or hepatitis B Participant has had major surgery (eg, requiring general anesthesia) within the 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned through the course of the study Participant has had a thyroidectomy or active thyroid disease requiring medication during the last 12 months (not excluded: a stable thyroid supplementation) Current or past drug/alcohol use that investigator assesses poses any more than a remotely increased risk of the ability of the participant to comply with the protocol requirements Has been in receipt of any licensed vaccine within 14 days prior to the first dose of study vaccine or placebo, plans to receive within 14 days after the first study vaccination, or plans to receive within 14 days before or after the second, third or fourth vaccination Is a recipient of a prophylactic or therapeutic HIV vaccine candidate at any time, or a recipient of other experimental vaccine(s) within the last 12 months prior to the Day 1 visit (Vaccination 1). For participants who received an experimental vaccine (except HIV vaccine) more than 12 months prior to the Day 1 visit (Vaccination 1), documentation of the identity of the experimental vaccine must be provided to the sponsor, who will determine eligibility on a case-by-case basis

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Ad26.Mos4.HIV + Clade C gp140<br>Participants will receive Ad26.Mos4.HIV vaccine at Week 0 and 12, followed by Ad26.Mos4.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 microgram (mcg) of total protein mixed with adjuvant (aluminium phosphate) at Week 24 and 48. Participants who receive all 4 vaccinations and are negative for HIV infection at Week 72 can consent to be included in a long-term extension (LTE) phase (approximately 3 years after Week 72). | Biological: Ad26.Mos4.HIV<br>* Ad26.Mos4.HIV at a dose of 5*10^10 viral particles (vp), administered intramuscularly.<br>Biological: Clade C gp140 plus adjuvant<br>* Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 milliliter (mL) injection administered intramuscularly.<br>|
| Experimental: Group 2: Ad26.Mos4.HIV + Clade C gp140 + Mosaic gp140<br>Participants will receive Ad26.Mos4.HIV vaccine at Week 0 and 12; followed by Ad26.Mos4.HIV vaccine + combination of 125 mcg Mosaic gp140 and 125 mcg Clade C gp140 mixed with adjuvant (aluminum phosphate) at Week 24 and 48. Participants who receive all 4 vaccinations and are negative for HIV infection at Week 72 can consent to be included in a long-term extension (LTE) phase (approximately 3 years after Week 72). | Biological: Ad26.Mos4.HIV<br>* Ad26.Mos4.HIV at a dose of 5*10^10 viral particles (vp), administered intramuscularly.<br>Biological: Clade C gp140/Mosaic gp140 plus adjuvant<br>* Clade C gp140 and Mosaic gp140 (each 125 mcg of total protein) mixed with aluminum phosphate adjuvant, per 0.5 milliliter (mL) injection, administered intramuscularly.<br>|
| Placebo Comparator: Group 3: Placebo<br>Participants will receive a single placebo injection at Weeks 0 and 12, followed by two placebo injections at Weeks 24 and 48. | Other: Placebo<br>* Placebo Containing 0.9 percent normal saline, administered intramuscularly.<br>|
| Experimental: Group 1b: Ad26.Mos4.HIV + gp140 HIV Bivalent Vaccine<br>Participants enrolled in the LTE phase will receive late boost vaccination Ad26.Mos4.HIV and bivalent gp140 within 4 weeks prior to Week 192 until 4 months after Week 192 (that is, approximately 3 years after the 4th vaccination of the primary vaccination series). | Biological: Ad26.Mos4.HIV<br>* Ad26.Mos4.HIV at a dose of 5*10^10 viral particles (vp), administered intramuscularly.<br>Biological: gp140 HIV Bivalent Vaccine<br>* gp140 HIV Bivalent Vaccine is adjuvanted protein co-formulation with a dosage strength of 80 mcg Clade C protein, 75 mcg Mosaic protein and 425 mcg aluminum (as aluminum phosphate adjuvant).<br>|
| Placebo Comparator: Group 2b: Placebo<br>Participants will receive placebo injection at Week 192 -4 weeks/+4 months, that is, approximately 3 years after the 4th vaccination of the primary vaccination series. | Other: Placebo<br>* Placebo Containing 0.9 percent normal saline, administered intramuscularly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local and Systemic Adverse Events (AEs) | Number of Participants With Solicited Local and Systemic Adverse Events (AEs) | Baseline up to 7 days after each vaccination | 
| Number of Participants With Adverse events (AEs) | Number of Participants With Adverse events (AEs) | Baseline up to 28 days after each vaccination | 
| Discontinuations From Vaccination/From Study due to AEs | Discontinuations From Vaccination/From Study due to AEs | Baseline up to Week 72 | 
| Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) of Confirmed Human Immunodeficiency Virus (HIV) Infection | Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) of confirmed HIV infection. | Baseline up to Week 288 | 
| Envelope (Env)-specific Binding Antibody (Abs) (Titers and Breadth) | Envelope (Env)-specific Binding Antibody (Abs) (Titers and Breadth) | Baseline up to Week 216 | 
| Number of Participants with AESIs of Thrombosis With Thrombocytopenia Syndrome (TTS) | Number of participants with AESIs of TTS will be reported. Thrombotic events and/or symptomatic thrombocytopenia are considered to be potential AESIs. | Baseline up to Week 216 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Env-specific Neutralizing Antibody (nAbs) (Titers and Breadth) (for Tier 1 and Tier 2 Viruses) | Env-specific Neutralizing Antibody (nAbs) (Titers and Breadth) (for Tier 1 and Tier 2 Viruses) | Baseline up to Week 288 | 
| Env-specific Functional Abs (Phagocytosis Score and Breadth) | Env-specific Functional Abs (Phagocytosis Score and Breadth) | Baseline up to Week 288 | 
| Env-specific Binding Ab Isotypes (Immunoglobulin A [IgA], IgG1-4) (Titers and Breadth) | Env-specific Binding Ab Isotypes (Immunoglobulin A [IgA], IgG1-4) (Titers and Breadth) | Baseline up to Week 288 | 
| Interferon (IFN)-gamma Peripheral Blood Mononuclear Cell (PBMC) Responders to Mosaic and Potential T-cell Epitope (PTE) peptide pools of Env/Group-specific Antigen (Gag)/ Polymerase (Pol) | Interferon (IFN)-gamma Peripheral Blood Mononuclear Cell (PBMC) Responders to Mosaic and Potential T-cell Epitope (PTE) peptide pools of Env/Group-specific Antigen (Gag)/ Polymerase (Pol) | Baseline up to Week 288 | 
| Cluster of Differentiation (Cd)4+ and Cd8+ T-Cell Functionality (Percentage [%] Cells Producing I-alpha, IFN-gamma, Interleukin [IL-2], IL-4, Tumor Necrosis Factor [TNF]-alpha) | Cluster of Differentiation (Cd)4+ and Cd8+ T-Cell Functionality (Percentage [%] Cells Producing I-alpha, IFN-gamma, Interleukin [IL-2], IL-4, Tumor Necrosis Factor [TNF]-alpha) | Baseline up to Week 288 | 
| T-Cell Development With Emphasis on Follicular Helper T-Cells and Memory Differentiation | T-Cell Development With Emphasis on Follicular Helper T-Cells and Memory Differentiation | Baseline up to Week 288 |