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

Healthy Clinical Trial

— IPCAVD-012  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02935686
• Other study ID #: CR108207
• Secondary ID: VAC89220HPX2003
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 31, 2017
• Est. completion date: November 22, 2023

Study information

• Verified date: April 2024
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: November 22, 2023
• Est. primary completion date: November 22, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Biological:
• Ad26.Mos4.HIV
Ad26.Mos4.HIV at a dose of 5*10^10 viral particles (vp), administered intramuscularly.
• Clade C gp140 plus adjuvant
Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 milliliter (mL) injection administered intramuscularly.
• Clade C gp140/Mosaic gp140 plus adjuvant
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.

Other:
• Placebo
Placebo Containing 0.9 percent normal saline, administered intramuscularly.

Biological:
• gp140 HIV Bivalent Vaccine
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).

Locations

Country	Name	City	State
Kenya	Walter Reed Project Clinical Research Center	Kericho
Rwanda	Center for Family Health Research/Project San Francisco	Kigali
United States	Alabama Vaccine Research Clinic at UAB	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Fenway Health	Boston	Massachusetts
United States	The Hope Clinic at Emory University	Decatur	Georgia
United States	Columbia University HIV Vaccine Unit	New York	New York
United States	New York Blood Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Strong Memorial Infectious Disease	Rochester	New York
United States	Bridge HIV	San Francisco	California
United States	Seattle Vaccine Trials Unit	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Countries where clinical trial is conducted

United States,  Kenya,  Rwanda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Participants With Adverse events (AEs)	Number of Participants With Adverse events (AEs)	Baseline up to 28 days after each vaccination
Primary	Discontinuations From Vaccination/From Study due to AEs	Discontinuations From Vaccination/From Study due to AEs	Baseline up to Week 72
Primary	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
Primary	Envelope (Env)-specific Binding Antibody (Abs) (Titers and Breadth)	Envelope (Env)-specific Binding Antibody (Abs) (Titers and Breadth)	Baseline up to Week 216
Primary	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	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
Secondary	Env-specific Functional Abs (Phagocytosis Score and Breadth)	Env-specific Functional Abs (Phagocytosis Score and Breadth)	Baseline up to Week 288
Secondary	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
Secondary	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
Secondary	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
Secondary	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