The purpose of this study is to assess the safety and tolerability of various regimens containing adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV), Modified Vaccinia Ankara (MVA)-Mosaic, and/or HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) components and to compare envelope binding antibody responses between the different vaccine regimens.
This is a multicenter (more than 1 hospital or medical school team work on a study), randomized (the study drug is assigned by chance), parallel group (each group of participants will be treated at the same time), placebo-controlled (study in which the experimental treatment or procedure is compared to a pretend treatment with no drug in it to test if the drug has a real effect), and double-blind (neither physician nor participant knows the treatment that the participant receives) study. All eligible participants will be randomly assigned to receive 1 of the 8 vaccine regimens. Participants will receive study vaccines (Ad26.Mos.HIV, MVA-Mosaic, gp140 DP, and placebo) 4 times as per assigned regimen. The study comprises a Screening Period (up to 4 weeks), a Vaccination Period (participants will be vaccinated at Baseline (Week 0), Week 12, Week 24 and Week 48), and a Follow-up Period (up to 48 weeks). A long-term follow-up period (approximately 2 years after Week 96) will continue for participants randomized to the regimen subsequently selected for future studies, based on analysis of Week 28 data. If Week 28 data are inconclusive, Week 52 data will be considered for regimen selection. If no clear decision can be made, the extended follow-up period could include participants from more than 1 group for assessing durability of immune responses. Participants' safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
393
Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelop (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 live attenuated MVA virus-vectored vaccine that has been genetically engineered to express 2 mosaic Gag, Pol, and Env sequences (Mosaic 1 and Mosaic 2). Total dose is 10\^8 plaque-forming unit per 0.5 mL injection administered intramuscularly.
The gp140 DP vaccine containing 50 mcg of total protein, mixed with aluminum phosphate adjuvant (0.425 mg aluminum), per 0.5 mL injection administered intramuscularly.
The gp140 DP vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Normal saline, 0.5 mL injection administered intramuscularly.
Unnamed facility
Aurora, Colorado, United States
Unnamed facility
Miami, Florida, United States
Unnamed facility
Rockville, Maryland, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Austin, Texas, United States
Unnamed facility
Kigali, Rwanda
Unnamed facility
Cape Town, South Africa
Unnamed facility
Durban, South Africa
Unnamed facility
Johannesburg, South Africa
Unnamed facility
Bangkok, Thailand
...and 2 more locations
Percentage of Participants With Solicited Local Adverse Events (AEs) Post Vaccination
Solicited local AEs (at injection site) included erythema, induration, swelling, itching and warmth were collected within 7 days after vaccination.
Time frame: Up to Week 49 (7 days post any dose)
Percentage of Participants With Solicited Systemic Adverse Events (AEs) Post Vaccination
Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), headache, fatigue, myalgia, nausea, vomiting were collected within 7 days after vaccination.
Time frame: Up to Week 49 (7 days post any dose)
Percentage of Participants With Unsolicited Adverse Events Post Vaccination
Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.
Time frame: Up to Week 52 (28 days post vaccination)
Number of Participants With Serious Adverse Events (SAEs) Post Vaccination
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study vaccine. An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product.
Time frame: Serious adverse events (SAEs) were reported up to Week 336 for Group 1 and 2 and up to Week 96 for the other groups (Group 3, 4, 5, 6, 7, and 8). Other adverse events (AEs) were reported for the main study period up to Week 96 for all the groups
Percentage of Responders for Envelop (Env) Clade A, B and C-specific Binding Antibody Titers at Week 28
The Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)- specific binding antibody titer 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 less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline greater than or equal to (\>=) LLOQ. The lower limits of quantification (LLOQs) for this assay were 625, 156.25, 625, and 156.25 endotoxin units per milliliter (EU/mL) for Clade A (92UG037.1), Clade B (1990a), Clade C (Con C), and Clade C (C97ZA.012) respectively.
Time frame: Week 28
Percentage of Responders for Clade C (C97ZA.012) Env Enzyme-linked Immunosorbent Assay (ELISA) Immunoglobulin G1 (IgG1), IgG2, IgG3 and IgG4 Glycoprotein (gp) 140 Binding Antibody
Vaccine-induced binding antibody IgG1, IgG2, IgG3 and IgG4 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, 28.7, 12.4, and 13.2 for IgG1, IgG2, IgG3 and IgG4 respectively. Samples taken after Week 48 (W48) from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.
Time frame: Week 28, 52 and 96
Percentage of Responders for Env ELISA Including Consensus C and Mos1 Antigens
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 LLOQ for this assay is a 50 percent (%) inhibitory concentration (IC50) of 20 (fold-dilution). The lower limits of quantification (LLOQs) for this assay were 625 and 78.125 EU/mL for Clade C (Con C) and Mos1 respectively. Samples taken after W48 from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.
Time frame: Week 28, 52 and 96
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 \<LOD or missing or defined as post-baseline value \>3-fold increase from baseline if baseline \>=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. Samples taken after W48 from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category of Clade A, B, C and Mos 1.
Time frame: Week 16, 26, 28, 52, 78, and 96
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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 is an inhibitory concentration (IC50) of 20 (fold-dilution). Data reported for the responses against Tier 1 HIV strain Clade C (MW965.26) was reported. Samples taken after W48 from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.
Time frame: Week 28 and 52
Percentage of Responders for Binding Antibody Multiplex Assay (BAMA) IgG1-IgG4 and IgA and IgG-t Breadth Antibody
The human immunodeficiency virus (HIV)-1 BAMA employs flow-cytometric-based technology that also utilizes antibody and antigen interactions to test for the presence of specific antibodies in an unknown sample with the added advantage of multiplexing the antigens of interest. Positive and negative control standards were run with each assay to ensure specificity. The positivity threshold was determined per antigen based on the plus (+) 3 standard deviation (SD) on the non-specific background. Sample values had to be greater than or equal to this value and had to be 3-fold over the baseline values with a minimum median fluorescent intensities (MFI) value of 100. Samples taken after W48 from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.
Time frame: Week 16, 28, 52, 78, and 96
Percentage of Responders With Interferon-gamma (IFN-gamma) T Cell Responses 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. The threshold for ELISpot test was based on the 95th percentile (P95) from the baseline values of participants on that test in the study. Samples taken after W48 from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.
Time frame: Week 26, 50, 78 and 96