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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
201
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.
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.
Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Normal saline 0.9 percent (%), 0.5 mL injection administered intramuscularly.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
San Francisco, California, United States
Unnamed facility
Decatur, Georgia, United States
Unnamed facility
Silver Spring, Maryland, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Rochester, New York, United States
Unnamed facility
Philadelphia, Pennsylvania, United States
Unnamed facility
Seattle, Washington, United States
Unnamed facility
Kigali, Rwanda
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Week 72
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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Weeks 28, 52 and 72
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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.
Time frame: 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.
Time frame: Up to Week 264