Safety, Tolerability and Immunogenicity Study of Different Vaccine Regimens of Trivalent Ad26.Mos.HIV or Tetravalent Ad26.Mos4.HIV Along With Clade C Glycoprotein (gp)140 in Healthy Human Immunodeficiency Virus (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/tolerability of the 2 different vaccine regimens of priming with trivalent Ad26.Mos.HIV and boosting with trivalent Ad26.Mos.HIV and Clade C gp140 plus adjuvant or priming with tetravalent Ad26.Mos4.HIV and boosting with Ad26.Mos4.HIV and Clade C glycoprotein (gp)140 plus adjuvant. Immune responses of the different vaccine schedules will be assessed.

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 the Safety/Tolerability and Immunogenicity of 2 Different Prime/Boost Regimens; Priming With Trivalent Ad26.Mos.HIV and Boosting With Trivalent Ad26.Mos.HIV And Clade C Gp140 Plus Adjuvant or Priming With Tetravalent Ad26.Mos4.HIV and Boosting With Tetravalent Ad26.Mos4.HIV and Clade C Gp140 Plus Adjuvant

Conditions
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Healthy

Intervention / Treatment
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* Biological: Ad26.Mos.HIV
* Biological: Ad26.Mos4.HIV
* Biological: Clade C gp140
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are negative for human immunodeficiency virus (HIV) infection at screening Is healthy on the basis of physical examination, medical history, electrocardiogram (ECG), and vital signs measurement performed at screening Are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures Female participants of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [beta hCG]) at the Screening visit, and a negative urine pregnancy test pre-dose on Day 1 Are assessed by the clinic staff as being at low risk for HIV infection 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] PCR test will be used to confirm active versus past HCV infection), active syphilis infection, chlamydia, gonorrhea, or trichomonas . Active syphilis documented by serology unless positive serology is due to past treated infection Has had a thyroidectomy or active thyroid disease requiring medication during the last 12 months (not excluded: a stable thyroid supplementation) Has had major psychiatric illness and/or substance abuse problems during the past 12 months (including hospitalization or periods of work disability) that in the opinion of the investigator would preclude participation Has been in receipt of any licensed vaccine within 14 days prior to the first dose of study vaccine/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
Maximum Age: 50 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 1A: Ad26.Mos.HIV<br>Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12, followed by Ad26.Mos.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 micrograms (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48. | Biological: Ad26.Mos.HIV<br>* Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelope (Env) sequence, and 2 vectors containing mosaic inserts of Gag and Pol sequences (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol). Total dose is 5*10^10 viral particle per 0.5 milliliter (mL) injection administered intramuscularly.<br>Biological: Clade C gp140<br>* Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.<br>|
| Placebo Comparator: Group 1B: Placebo<br>Participants will receive placebo at Weeks 0, 12, 24 and 48. | Drug: Placebo<br>* Normal saline 0.9 percent (%), 0.5 mL injection administered intramuscularly.<br>|
| Experimental: Group 2A: Ad26.Mos4.HIV<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 micrograms (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48. Participants will be included in an optional Long-term Extension (LTE) phase (3 years or 4 years Follow-up after Week 72, every 6 months visit) to assess immunogenicity and safety (serious adverse events [SAEs]). | Biological: Ad26.Mos4.HIV<br>* Recombinant replication-deficient Ad26 vectored vaccine and consists of 4 Ad26 vectors, 2 containing a mosaic insert of envelope (Env) sequence, and 2 vectors containing mosaic inserts of Gag and Pol sequences (Ad26.Mos.1.Env + Ad26.Mos.2S.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol). Total dose is 5*10^10 viral particle per 0.5mL injection administered intramuscularly.<br>Biological: Clade C gp140<br>* Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.<br>|
| Placebo Comparator: Group 2B: Placebo<br>Participants will receive placebo at Weeks 0, 12, 24 and 48. | Drug: Placebo<br>* Normal saline 0.9 percent (%), 0.5 mL injection administered intramuscularly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Local Adverse Events (AEs) Post First Vaccination | Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination. | 7 days after first vaccination on Day 1 (Day 8) | 
| Percentage of Participants With Solicited Local AEs Post Second Vaccination | Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination. | 7 days after second vaccination on Day 85 (Day 92) | 
| Percentage of Participants With Solicited Local AEs Post Third Vaccination | Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination. | 7 days after third vaccination on Day 169 (Day 176) | 
| Percentage of Participants With Solicited Local AEs Post Fourth Vaccination | Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination. | 7 days after fourth vaccination on Day 337 (Day 344) | 
| Percentage of Participants With Solicited Systemic AEs Post First Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination. | 7 days after first vaccination on Day 1 (Day 8) | 
| Percentage of Participants With Solicited Systemic AEs Post Second Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination. | 7 days after second vaccination on Day 85 (Day 92) | 
| Percentage of Participants With Solicited Systemic AEs Post Third Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination. | 7 days after third vaccination on Day 169 (Day 176) | 
| Percentage of Participants With Solicited Systemic AEs Post Fourth Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination. | 7 days after fourth vaccination on Day 337 (Day 344) | 
| Percentage of Participants With Unsolicited AEs for 28 Days After First Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as solicited AEs and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days. | 28 days after first vaccination on Day 1 (Day 29) | 
| Percentage of Participants With Unsolicited AEs for 28 Days After Second Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as solicited AEs and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days. | 28 days after second vaccination on Day 85 (Day 113) | 
| Percentage of Participants With Unsolicited AEs for 28 Days After Third Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as solicited AEs and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days. | 28 days after third vaccination on Day 169 (Day 197) | 
| Percentage of Participants With Unsolicited AEs for 28 Days After Fourth Vaccination | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as solicited AEs and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days. | 28 days after fourth vaccination on Day 334 (Day 362) | 
| Percentage of Participants With Discontinuations From Vaccination Due to AEs | Percentage of participants with discontinuations from vaccination due to AEs were reported. | Up to Week 72 | 
| Percentage of Participants With Serious Adverse Events (SAEs) During Main Study | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. SAE was defined as any AE that resulted in: death, persistent or significant disability/incapacity, required inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, was a congenital anomaly/birth defect and would jeopardize participant and/or required medical or surgical intervention to prevent one of the outcomes listed above. | Up to Week 72 | 
| Percentage of Participants With SAEs During Long Term Extension (LTE) Period | An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. SAE was defined as any AE that resulted in: death, persistent or significant disability/incapacity, required inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, was a congenital anomaly/birth defect and would jeopardize participant and/or required medical or surgical intervention to prevent one of the outcomes listed above. This outcome measure was planned to be analyzed for specified arm only. | From Week 96 to Week 264 | 
| Percentage of Participants With AEs of Special Interest During Main Study | Percentage of participants with AEs of special interest during main study were reported. HIV infection was considered as an AE of special interest. | Up to Week 72 | 
| Percentage of Participants With AEs of Special Interest During LTE Period | Percentage of participants with AEs of special interest during LTE period were reported. HIV infection was considered as an AE of special interest. This outcome measure was planned to be analyzed for specified arm only. | From Week 96 to Week 264 | 
| Percentage of Responders for Envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) Specific Binding Antibody Titers at Week 28 | Percentage of responders for envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) specific binding antibody titers at Week 28 were reported. Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)-specific binding antibody titers were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (>) lower limit of quantification (LLOQ) if baseline value less than (<) LLOQ or missing or defined as post-baseline value >3-fold increase from baseline if baseline value greater than or equal to (>=) LLOQ. | Week 28 | 
| Percentage of Responders for Envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) Specific Binding Antibody Titers at Week 52 | Percentage of responders for envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) specific binding antibody titers at Week 52 were reported. Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)-specific binding antibody titers were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (>) lower limit of quantification (LLOQ) if baseline value less than (<) LLOQ or missing or defined as post-baseline value >3-fold increase from baseline if baseline value greater than or equal to (>=) LLOQ. | Week 52 | 
| Percentage of Responders for Envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) Specific Binding Antibody Titers at Week 72 | Percentage of responders for envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) specific binding antibody titers at Week 72 were reported. Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)-specific binding antibody titers were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (>) lower limit of quantification (LLOQ) if baseline value less than (<) LLOQ or missing or defined as post-baseline value >3-fold increase from baseline if baseline value greater than or equal to (>=) LLOQ. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders for Human Immunodeficiency Virus Neutralizing Antibody (HIV nAb) | The functionality of vaccine-induced antibody responses was investigated by the determination of nAb activity in a virus neutralization assay (VNA) using TZM-bl cells and Env-pseudotyped viruses. The response was defined as post-baseline value >LLOQ. The LLOQ for this assay was an inhibitory concentration (IC50) of 20 (fold-dilution). The data was collected for the responses against Tier 1 HIV strain Clade C (MW965.26 and C97ZA.012). | Weeks 28, 52 and 72 | 
| Percentage of Responders for Env Antibody-dependent Cellular Phagocytosis (ADCP) gp Antibody | The functionality of vaccine-induced antibody responses was investigated by the determination of ADCP. The response was defined as post-baseline value > limit of detection (LOD) if baseline value <LOD or missing or defined as post-baseline value >3-fold increase from baseline if baseline value >=LOD. The lower limits of detection (LODs) for this assay were 5.16, 6.43, 6.49, 4.32 and 4.28 (phagocytic score) for Clade A (92UG037.1), Clade B (1990a), Clade C (Con C), Clade C (C97ZA.012), and Mos1, respectively. | Weeks 28, 52 and 72 | 
| Percentage of Responders With Interferon-gamma (IFN-gamma) T Cell Responses Assessed Using Enzyme-linked Immunospot Assay (ELISpot) | Frozen peripheral blood mononuclear cell (PBMCs) were analyzed by interferon-gamma (IFN-gamma) (ELISpot). The response was defined as post-baseline value >P95 if baseline <P95 or missing or defined as post-baseline value >3-fold increase from baseline if baseline >=P95. | Weeks 26, 52 and 72 | 
| Percentage of Responders for Immunoglobulin G1 (IgG1) and IgG3 Gylcoprotein (gp) 140 Binding Antibody Assessed Using Clade C (C97ZA.012) Env Enzyme-linked Immunosorbent Assay (ELISA) | Vaccine-induced binding antibody IgG1 and IgG3 subclass responses were investigated using Clade C (C97ZA.012) specific ELISAs. The response was defined as post-baseline value >LLOQ if baseline <LLOQ or missing or defined as post-baseline value >3-fold increase from baseline if baseline >=LLOQ. The LLOQs for this assay were 12.3 and 12.4 for IgG1 and IgG3, respectively. | Weeks 28, 52 and 72 | 
| Percentage of Responders for CD4+ and CD8+ T-Cell Responses | Intracellular cytokine staining (ICS) was performed to examine the type of T-cell responding to vaccination. Responder definition was based on the Fisher's exact text between cytokine producing cells and non-producing cells in stimulated versus non-stimulated conditions. | Weeks 28, 52 and 72 | 
| Percentage of Participants With T-cell Development | As per change in planned analysis, this outcome measure was not performed since it was no longer considered relevant to interpret the immunogenicity of the vaccines. | Up to Week 264 |