Safety, Tolerability and Immunogenicity Study of Different Vaccine Regimens of Trivalent Ad26.Mos.HIV or Tetravalent Ad26.Mos4.HIV Along With Clade C Glycoprotein (gp)140 in Healthy Human Immunodeficiency Virus (HIV)-Uninfected Adults

• ClinicalTrials.gov Identifier: NCT02788045
• Recruitment Status: Active, not recruiting
• First Posted: June 2, 2016
• Last Update Posted: June 11, 2020
• Sponsor: Janssen Vaccines & Prevention B.V.
• Information provided by (Responsible Party): Janssen Vaccines & Prevention B.V.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Biological: Ad26.Mos.HIV; Biological: Ad26.Mos4.HIV; Biological: Clade C gp140; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Parallel-Group, Placebo-Controlled, Double-Blind Phase 1/2a Study in Healthy HIV Uninfected Adults to Assess the Safety/Tolerability and Immunogenicity of 2 Different Prime/Boost Regimens; 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 Tetravalent Ad26.Mos4.HIV and Clade C Gp140 Plus Adjuvant
• Actual Study Start Date: July 8, 2016
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: June 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1A: Ad26.Mos.HIV; Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12, followed by Ad26.Mos.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 microgram (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48.	Biological: Ad26.Mos.HIV; 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.; Biological: Clade C gp140; Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Placebo Comparator: Group 1B: Placebo; Participants will receive placebo at Weeks 0, 12, 24 and 48.	Drug: Placebo; Normal saline 0.9 percent (%), 0.5 mL injection administered intramuscularly.
Experimental: Group 2A: Ad26.Mos4.HIV; 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 (aluminum phosphate) at Week 24 and 48. Participants will be included in an optional Long-term Extension (LTE) phase (3 years or 5 years Follow-up after Week 72, every 6 months visit) to assess immunogenicity and safety (serious adverse events [SAEs]).	Biological: Ad26.Mos4.HIV; 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.; Biological: Clade C gp140; Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Placebo Comparator: Group 2B: Placebo; Participants will receive placebo at Weeks 0, 12, 24 and 48.	Drug: Placebo; Normal saline 0.9 percent (%), 0.5 mL injection administered intramuscularly.

Outcome Measures

Primary Outcome Measures :

1. Local And Systemic Solicited Adverse Events (Aes) for 7 Days Post-Vaccination [ Time Frame: Baseline up to 7 days after each vaccination ]
   Participants will be asked to note occurrences of local reactions: pain/tenderness, erythema, swelling/induration at the injection site, and systemic events: fever (temperature measurement), fatigue, headache, nausea, myalgia and chills daily for 7 days post-vaccination.
2. AEs for 28 Days After Each Vaccination [ Time Frame: Baseline up to 28 days after each vaccination ]
3. Discontinuations From Vaccination/From Study Due to AEs [ Time Frame: Baseline up to Week 72 ]
4. Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) During the Course of the Study, Including the Optional LTE Phase [ Time Frame: Baseline up to Week 312 ]
5. Envelope (Env)-specific Binding Antibody (Abs) (Titers and Breadth) [ Time Frame: Baseline up to Week 312 ]

Secondary Outcome Measures :

1. Env-specific Neutralizing Antibody (nAbs) (Titers and Breadth) (for Tier 1 and Tier 2 Viruses) [ Time Frame: Baseline up to Week 312 ]
2. Env-specific Functional Abs (Phagocytosis Score and Breadth) [ Time Frame: Baseline up to Week 312 ]
3. Env-specific Binding Ab Isotypes (Immunoglobulin A [Iga], Igg1-4) (Titers and Breadth) [ Time Frame: Baseline up to Week 312 ]
4. Interferon (IFN)-gamma Peripheral Blood Mononuclear Cell (PBMC) Responders to Mosaic Peptide Pools of Env/Group-specific Antigen (Gag)/Polymerase (Pol) and Potential T-cell Epitope (PTE) [ Time Frame: Baseline up to Week 312 ]
5. 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) [ Time Frame: Baseline up to Week 312 ]
6. T-Cell Development With Emphasis on Follicular Helper T-Cells and Memory Differentiation [ Time Frame: Baseline up to Week 72 ]
7. Available Samples From Time Points After Last Vaccination Until the Final Main Study Visit at Week 72 Will be Used for Determination of Durability of the Immune Responses [ Time Frame: Baseline up to Week 72 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Are negative for human immunodeficiency virus (HIV) infection at screening
• Is healthy on the basis of physical examination, medical history, electrocardiogram (ECG), and vital signs measurement performed at screening
• Are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures
• Female participants of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [beta hCG]) at the Screening visit, and a negative urine pregnancy test pre-dose on Day 1
• Are assessed by the clinic staff as being at low risk for HIV infection

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] PCR test will be used to confirm active versus past HCV infection), active syphilis infection, chlamydia, gonorrhea, or trichomonas . Active syphilis documented by serology unless positive serology is due to past treated infection
• Has had a thyroidectomy or active thyroid disease requiring medication during the last 12 months (not excluded: a stable thyroid supplementation)
• Has had major psychiatric illness and/or substance abuse problems during the past 12 months (including hospitalization or periods of work disability) that in the opinion of the investigator would preclude participation
• Has been in receipt of any licensed vaccine within 14 days prior to the first dose of study vaccine/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

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States

United States, California

San Francisco, California, United States

United States, Georgia

Decatur, Georgia, United States

United States, Maryland

Silver Spring, Maryland, United States

United States, Massachusetts

Boston, Massachusetts, United States

United States, New York

New York, New York, United States

Rochester, New York, United States

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

United States, Washington

Seattle, Washington, United States

Rwanda

Kigali, Rwanda

Sponsors and Collaborators

Janssen Vaccines & Prevention B.V.

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial; Janssen Vaccines & Prevention B.V.

More Information

• Responsible Party: Janssen Vaccines & Prevention B.V.
• ClinicalTrials.gov Identifier: NCT02788045
• Other Study ID Numbers: CR108152; VAC89220HPX2004 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
• First Posted: June 2, 2016
• Last Update Posted: June 11, 2020
• Last Verified: June 2020

• Studies a U.S. FDA-regulated Device Product: No