This is a Phase I, randomized, double-blind, placebo-controlled clinical study to define the safety and immunogenicity resulting from a rapid dose-escalating vaccination schedule as compared to that of a co-administered, dose-consistent vaccination schedule. Participants randomized to receive vaccines will get either dose-consistent injections of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV or rapid, dose-escalating injections of CH505 TF chTrimer+ALFQ with an Ad26.Mos4.HIV prime, followed by dose-consistent injection of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV
Male or female, aged 18 to 50 years, inclusive, at the time of enrollment
Willing and able to read, sign, and date the informed consent form
Demonstrates an understanding of the study with a passing score (90% or greater) on the TOU by the third attempt, before study-related procedures are performed
Willing and able to comply with study requirements and be available to attend visits for the duration of study participation
first diagnosed within the 12 weeks prior to screening; or
worsening in terms of clinical outcome in the 24 weeks prior to screening; or
involves the need for medication that may pose a risk to the participant's safety or impede assessment of adverse events or immunogenicity if they participate in the study.
Hemoglobin ≥11.0 g/dL for females; ≥12.5 g/dL for males
Parallel
Ad26.Mos4.HIV in CH505 TF chTrimer + ALFQ [Arm 1a]
Biological/VaccineParticipants in Arm 1a will receive dose consistent injections (5x10\^10 vp/0.5 mL) of Ad26.Mos4.HIV in a 0.5 mL injection volume and dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1 and 57
CH505 TF chTrimer + ALFQ [Arm 1a]
Biological/VaccineParticipants in Arm 1a will receive a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169.
Placebo [Arm 1a]
Biological/VaccineParticipants in Arm 1a will receive dose-consistent 0.5 mL injection and a 1.1 mL injection of Placebo on Study Days 1 and 57, followed by a 1.1 mL injection of Placebo on Study Day 169.
Ad26.Mos4.HIV in CH505 TF chTrimer +ALFQ [Arm 2a]
Biological/VaccineParticipants in Arm 2a will receive a lower dose of Ad26.Mos4.HIV (2.5x10\^10 vp/0.25 mL) in a 0.25 mL injection volume and a lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS-21) in a 0.5 mL injection volume on Study Day 1. Participants in Arm 2a will receive an injection Ad26.Mos4.HIV (5x10\^10 vp/0.5 mL) in a 0.5 mL injection volume and CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 57.
CH505 TF chTrimer +ALFQ [Arm 2a]
Biological/VaccineParticipants in Arm 2a will receive a rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume). Participants in Arm 2a will receive a injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169.
Placebo [Arm 2a]
Biological/VaccineParticipants in Arm 2a will receive a 0.25 mL injection and a 0.5 mL injection of Placebo on Study Day 1; followed by 0.5 mL, 0.5 mL, and 0.9 mL injections of Placebo on Study Days 4, 8, and 15, respectively; followed by a 0.5 mL injection and a 1.1 mL injection of Placebo on Study Day 57; followed by a 1.1 mL injection of Placebo on Study Day 169.
CH505 TF chTrimer + ALFQ [Arm 1b]
Biological/VaccineParticipants in Arm 1b will receive dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1, 57, and 169.
Placebo [Arm 1b]
Biological/VaccineParticipants in Arm 1b will receive a 1.1 mL injection of Placebo on Study Days 1, 57, and 169.
CH505 TF chTrimer + ALFQ [Arm 2b]
Biological/VaccineParticipants in Arm 2b will receive a lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) in a 0.5 mL injection volume on Study Day 1. Participants in Arm 2b will receive a rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume). Participants in Arm 2b will receive a injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Days 57 and 169.
Placebo [Arm 2b]
Biological/VaccineParticipants in Arm 2b will receive a 0.5 mL injection of Placebo on Study Days 1, 4, and 8; followed by a 0.9 mL injection of Placebo on Study Day 15; followed by a 1.1 mL injection of Placebo on Study Days 57 and 169.
Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration
Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration.
Occurrence, severity, and relationship to vaccination of unsolicited adverse events after candidate vaccine administration
Occurrence, severity, and relationship to vaccination of unsolicited adverse events after candidate vaccine administration.
Occurrence of serious adverse events (SAEs) following candidate vaccine administration
Occurrence of serious adverse events (SAEs) following candidate vaccine administration.
Occurrence of adverse events of special interest (AESIs) following candidate vaccine administration
Occurrence of adverse events of special interest (AESIs) following candidate vaccine administration.
Quantify IgG binding antibodies to HIV Env in terms of magnitude, breadth, and durability between Arms
Quantify IgG binding antibodies to HIV Env in terms of magnitude between Arms. HIV-specific Binding Antibody ELISA Assays will be performed to detect plasma IgG and IgA binding antibodies to HIV-1 Envelope antigens and assess their magnitude between Arms.
Quantify neutralizing antibodies to HIV Env in terms of magnitude, breadth, and durability between Arms
Quantify rate of neutralizing antibodies to HIV Env in terms of magnitude between Arms. Neutralizing Antibody Assays will be measured as a function of reductions in luciferase (Luc) reporter gene expression after a single round of infection in TZM-bl cells using high throughput analysis.
Characterize binding antibody Fc engagement to a panel of HIV Envs as assessed by Antibody Profiling
Characterize binding antibody Fc engagement to a panel of HIV Envs. Antibody Profiling will be conducted to assess antibody breadth and correlation of Fc receptor usage with antibody function.The current capacity for Antibody Profiling is the assessment of over 300 samples in one experiment. The beads presenting the HIV antigens will be distributed robotically in a high-throughput manner into 384 well plates. Similarly, the samples will be diluted robotically and incubated with the beads. Detection reagents will be added to the wells after washing. These detection reagents are inclusive of subclass, isotype, and Fc receptor usage.
Characterize rate of B-cell specificity by quantifying antigen-specific responses as assessed through B-cell ELISPOT
Characterize rate of B-cell specificity by quantifying antigen-specific responses as assessed through B-cell ELISPOT
Characterize magnitude of cell-mediated immune responses elicited across vaccination regimens (including antigen -specific CD4 and CD8 T cell responses) assessed by CD4 and CD8 cellular response assays and after stimulation with HIV-specific antigens.
Characterize and assess the magnitude of cell-mediated immune responses elicited across vaccination regimens including but not limited to antigen -specific CD4 and CD8 T cell responses as assessed by CD4 and CD8 cellular response assays and after stimulation with HIV-specific antigens.
Phenotype innate immune cells (NK cells) as assessed by flow cytometry
Characterize cytokines elicited by vaccine regimens
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U.S. Army Medical Research and Development Command
Lead sponsor
Janssen Vaccines & Prevention B.V.
Collaborator
Henry M. Jackson Foundation for the Advancement of Military Medicine
Collaborator
Duke University
Collaborator
Walter Reed Army Institute of Research (WRAIR)
Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Makerere University Walter Reed Project
Collaborator
