Clinical trial NCT02935686: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2016-10-17
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Main Study: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 7 Days Post-vaccination 1
timeFrame: Up to 7 days post-vaccination 1 on Day 1 (up to Day 8)
measure: Main Study: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 7 Days Post-vaccination 2
timeFrame: Up to 7 days post vaccination 2 (up to any day from Day 78 to Day 113) (vaccination 2 ranged from Day 78 to 106)
measure: Main Study: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 7 Days Post-vaccination 3
timeFrame: Up to 7 days post vaccination 3 (up to any day from Day 162 to Day 197) (vaccination 3 ranged from Day 162 to 190)
measure: Main Study: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 7 Days Post-vaccination 4
timeFrame: Up to 7 days post vaccination 4 (up to any day from Day 330 to Day 365) (vaccination 4 ranged from Day 330 to 358)
measure: Main Study: Number of Participants With Unsolicited Adverse Events (AEs) for 28 Days Post-vaccination 1
timeFrame: Up to 28 days post-vaccination 1 on Day 1 (Up to Day 29)
measure: Main Study: Number of Participants With Unsolicited Adverse Events (AEs) for 28 Days Post-vaccination 2
timeFrame: Up to 28 days post vaccination 2 (up to any day from Day 78 to Day 134) (vaccination 2 ranged from Day 78 to 106)
measure: Main Study: Number of Participants With Unsolicited Adverse Events (AEs) for 28 Days Post-vaccination 3
timeFrame: Up to 28 days post vaccination 3 (up to any day from Day 162 to Day 218) (vaccination 3 ranged from Day 162 to 190)
measure: Main Study: Number of Participants With Unsolicited Adverse Events (AEs) for 28 Days Post-vaccination 4
timeFrame: Up to 28 days post vaccination 4 (up to any day from Day 330 to Day 358) (vaccination 4 ranged from Day 330 to 358)
measure: Main Study: Number of Participants Who Discontinued Study Vaccination Due to AEs
timeFrame: From Baseline (Day 1) up to Week 72
measure: Main Study: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Baseline (Day 1) up to Week 72
measure: Main Study and LTE Study: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: From Baseline (Day 1) up to Week 216
measure: Late-boost (LB) Vaccination Phase: Number of Participants Who Discontinued Study Due to AEs
timeFrame: From Week 188 up to end of study (Week 288)
measure: Late-boost (LB) Vaccination Phase: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 7 Days Post Late Boost Vaccination
timeFrame: Up to 7 days post late boost vaccination (up to any day from Day 1317 to Day 1464) (late boost vaccination ranged from Day 1317 to 1457)
measure: Late-boost (LB) Vaccination Phase: Number of Participants With Unsolicited Adverse Events (AEs) for 28 Days Post Late Boost Vaccination
timeFrame: Up to 28 days post late boost vaccination (up to any day from Day 1317 to Day 1485) (late boost vaccination ranged from Day 1317 to 1457)
measure: Late-boost (LB) Vaccination Phase: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Week 188 up to end of study (Week 288)
measure: Late-boost (LB) Vaccination Phase: Number of Participants With AESIs of HIV Infection Up to End of Study
timeFrame: From Week 188 up to end of study (Week 288)
measure: Late-boost (LB) Vaccination Phase: Number of Participants With AESIs of Thrombosis With Thrombocytopenia Syndrome (TTS)
timeFrame: Up to 6 months post late boost vaccination (up to any day from Day 1317 to Day 1639) (late boost vaccination ranged from Day 1317 to 1457)
measure: Main Study: Geometric Mean of Envelope (Env) Clade A (92UG037.1), B (1990a), C (Con C), (C97ZA.012), Mos 1 Specific Binding Antibodies (Abs) Responses As Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 28
timeFrame: Week 28
measure: Main Study: Geometric Mean of Envelope (Env) Clade A (92UG037.1), B (1990a), C (Con C), (C97ZA.012), Mos 1 Specific Binding Antibodies (Abs) Responses As Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 52
timeFrame: Week 52
measure: Main Study: Geometric Mean of Envelope (Env) Clade A (92UG037.1) B (1990a), C (Con C), (C97ZA.012), Mos 1 Specific Binding Antibodies (Abs) Responses As Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 72
timeFrame: Week 72
measure: Main Study: Percentage of Responders for Envelope (Env)-Specific Binding Antibody Titers at Week 28
timeFrame: Week 28
measure: Main Study: Percentage of Responders for Envelope (Env)-Specific Binding Antibody Titers at Week 52
timeFrame: Week 52
measure: Main Study: Percentage of Responders for Envelope (Env)-Specific Binding Antibody Titers at Week 72
timeFrame: Week 72
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 192
timeFrame: Week 192
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 193
timeFrame: Week 193
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 196
timeFrame: Week 196
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 204
timeFrame: Week 204
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 216
timeFrame: Week 216
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 240
timeFrame: Week 240
measure: Late-boost (LB) Vaccination Phase: Geometric Mean of Envelope (Env) Mos 1 Specific Binding Antibodies (Abs) Response as Assessed Using Enzyme-linked Immunosorbent Assay (ELISA) at Week 288
timeFrame: Week 288
Secondary outcomes:
measure: Main Study: Percentage of Responders of Env-Specific Neutralizing Antibody (nAbs) for Tier 1 Viruses
timeFrame: Weeks 28, 52, and 72 (only for Clade C [MW965])
measure: Long-term Extension (LTE) Phase: Percentage of Responders of Env-Specific Neutralizing Antibody (nAbs) for Tier 1 Viruses
timeFrame: From Week 72 to Week 216
measure: Late-boost (LB) Vaccination Phase: Percentage of Responders of Env-Specific Neutralizing Antibody (nAbs) for Tier 1 Viruses
timeFrame: From Week 188 up to end of study (Week 288)
measure: Main Study: Percentage of Responders for Env-Specific Functional Antibody Response (Env ADCP gp140)
timeFrame: Weeks 28, 52, and 72 (Weeks 52 and 72 are only for HIV ENV [gp140 T sortA] C [ZA] F Ab)
measure: Long-term Extension (LTE) Phase: Percentage of Responders for Env-Specific Functional Antibody Response (Env ADCP gp140)
timeFrame: From Week 72 up to Week 216
measure: Late-boost (LB) Vaccination Phase: Percentage of Responders for Env-Specific Functional Antibody Response (Env ADCP gp140)
timeFrame: From Week 188 up to end of study (Week 288)
measure: Main Study: Percentage of Responders for Env-Specific Binding Ab Isotypes (Immunoglobulin [Ig] G1 and IgG3)
timeFrame: Weeks 28, 52, and 72
measure: Long-term Extension (LTE) Phase: Percentage of Responders for Env-Specific Binding Ab Isotypes (Immunoglobulin [Ig] G1 and IgG3)
timeFrame: From Week 72 up to Week 216
measure: Late-boost (LB) Vaccination Phase: Percentage of Responders for Env-Specific Binding Ab Isotypes (Immunoglobulin [Ig] G1 and IgG3)
timeFrame: From Week 188 up to end of study (Week 288)
measure: Main Study: Percentage of 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)
timeFrame: Weeks 28, 52, and 72
measure: Long-term Extension (LTE) Phase: Percentage of 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)
timeFrame: From Week 72 up to Week 216
measure: Late-boost (LB) Vaccination Phase: Percentage of 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)
timeFrame: From Week 188 up to end of study (Week 288)
measure: Main Study: Percentage of Responders With Cluster of Differentiation (CD)4+ and CD8+ T-Cell Functionality
timeFrame: Weeks 28, 52, and 72
measure: Long-term Extension (LTE) Phase: Percentage of Responders With Cluster of Differentiation (CD)4+ and CD8+ T-Cell Functionality
timeFrame: From Week 72 up to Week 216
measure: Late-boost (LB) Vaccination Phase: Percentage of Responders With Cluster of Differentiation (CD)4+ and CD8+ T-Cell Functionality
timeFrame: Weeks 192 and 196
measure: Main Study: Percentage of Participants With T-Cell Development
timeFrame: From Baseline (Day 1) up to Week 72
measure: Long-term Extension (LTE) Phase: Percentage of Participants With T-Cell Development
timeFrame: From Week 72 up to Week 216
measure: Late-boost (LB) Vaccination Phase: Percentage of Participants With T-Cell Development
timeFrame: From Week 188 up to end of study (Week 288)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine Research Clinic at UAB
state: Alabama
city: San Francisco
country: United States
facility: Bridge HIV
state: California
city: Decatur
country: United States
facility: The Hope Clinic at Emory University
state: Georgia
city: Boston
country: United States
facility: Brigham And Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Fenway Health
state: Massachusetts
city: New York
country: United States
facility: Columbia University HIV Vaccine Unit
state: New York
city: New York
country: United States
facility: New York Blood Center
state: New York
city: Rochester
country: United States
facility: Strong Memorial Infectious Disease
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Vaccine Trials Unit
state: Washington
city: Kericho
country: Kenya
facility: Walter Reed Project Clinical Research Center
city: Kigali
country: Rwanda
facility: Center for Family Health Research/Project San Francisco
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References: