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

NCT ID: NCT02935686

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-31
• Study Completion Date: 2023-11-22

Brief 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.

Detailed 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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Group 1: Ad26.Mos4.HIV + Clade C gp140

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 microgram (mcg) of total protein mixed with adjuvant (aluminium phosphate) at Week 24 and 48. Participants who receive all 4 vaccinations and are negative for HIV infection at Week 72 can consent to be included in a long-term extension (LTE) phase (approximately 3 years after Week 72).

Group Type: EXPERIMENTAL

Ad26.Mos4.HIV

Intervention Type: BIOLOGICAL

Ad26.Mos4.HIV at a dose of 5\*10\^10 viral particles (vp), administered intramuscularly.

Clade C gp140 plus adjuvant

Intervention Type: BIOLOGICAL

Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 milliliter (mL) injection administered intramuscularly.

Group 2: Ad26.Mos4.HIV + Clade C gp140 + Mosaic gp140

Participants will receive Ad26.Mos4.HIV vaccine at Week 0 and 12; followed by Ad26.Mos4.HIV vaccine + combination of 125 mcg Mosaic gp140 and 125 mcg Clade C gp140 mixed with adjuvant (aluminum phosphate) at Week 24 and 48. Participants who receive all 4 vaccinations and are negative for HIV infection at Week 72 can consent to be included in a long-term extension (LTE) phase (approximately 3 years after Week 72).

Group Type: EXPERIMENTAL

Ad26.Mos4.HIV

Intervention Type: BIOLOGICAL

Ad26.Mos4.HIV at a dose of 5\*10\^10 viral particles (vp), administered intramuscularly.

Clade C gp140/Mosaic gp140 plus adjuvant

Intervention Type: BIOLOGICAL

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.

Group 3: Placebo

Participants will receive a single placebo injection at Weeks 0 and 12, followed by two placebo injections at Weeks 24 and 48.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo Containing 0.9 percent normal saline, administered intramuscularly.

Group 1b: Ad26.Mos4.HIV + gp140 HIV Bivalent Vaccine

Participants enrolled in the LTE phase will receive late boost vaccination Ad26.Mos4.HIV and bivalent gp140 within 4 weeks prior to Week 192 until 4 months after Week 192 (that is, approximately 3 years after the 4th vaccination of the primary vaccination series).

Group Type: EXPERIMENTAL

Ad26.Mos4.HIV

Intervention Type: BIOLOGICAL

Ad26.Mos4.HIV at a dose of 5\*10\^10 viral particles (vp), administered intramuscularly.

gp140 HIV Bivalent Vaccine

Intervention Type: BIOLOGICAL

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).

Group 2b: Placebo

Participants will receive placebo injection at Week 192 -4 weeks/+4 months, that is, approximately 3 years after the 4th vaccination of the primary vaccination series.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo Containing 0.9 percent normal saline, administered intramuscularly.

Interventions

Ad26.Mos4.HIV

Ad26.Mos4.HIV at a dose of 5\*10\^10 viral particles (vp), administered intramuscularly.

Intervention Type: BIOLOGICAL

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: BIOLOGICAL

Placebo

Placebo Containing 0.9 percent normal saline, administered intramuscularly.

Intervention Type: OTHER

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).

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Vaccines & Prevention B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Vaccines & Prevention B.V. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Vaccines & Prevention B.V.

Locations

Alabama Vaccine Research Clinic at UAB

Birmingham, Alabama, United States

Bridge HIV

San Francisco, California, United States

The Hope Clinic at Emory University

Decatur, Georgia, United States

Brigham And Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Fenway Health

Boston, Massachusetts, United States

Columbia University HIV Vaccine Unit

New York, New York, United States

New York Blood Center

New York, New York, United States

Strong Memorial Infectious Disease

Rochester, New York, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Seattle Vaccine Trials Unit

Seattle, Washington, United States

Walter Reed Project Clinical Research Center

Kericho, , Kenya

Center for Family Health Research/Project San Francisco

Kigali, , Rwanda

Countries

United States; Kenya; Rwanda

References

Stieh DJ, Barouch DH, Comeaux C, Sarnecki M, Stephenson KE, Walsh SR, Sawant S, Heptinstall J, Tomaras GD, Kublin JG, McElrath MJ, Cohen KW, De Rosa SC, Alter G, Ferrari G, Montefiori D, Mann P, Nijs S, Callewaert K, Goepfert PA, Edupuganti S, Karita E, Seaman MS, Corey L, Baden LR, Pau MG, Schuitemaker H, Tomaka F; ASCENT/HVTN118/HPX2003 Study Team. Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults: A Phase 1/2a Study. J Infect Dis. 2023 Apr 18;227(8):939-950. doi: 10.1093/infdis/jiac445.

Reference Type: DERIVED

PMID: 36348617 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VAC89220HPX2003

Identifier Type: OTHER

Identifier Source: secondary_id

CR108207

Identifier Type: -

Identifier Source: org_study_id