Safety, Tolerability, and Immunogenicity Study of Homologous Ad26 Mosaic Vector Vaccine Regimens or Heterologous Ad26 Mosaic and MVA Mosaic Vector Vaccine Regimens With Glycoprotein 140 (gp140) for Human Immunodeficiency Virus (HIV) Prevention

NCT02315703 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: CR106152HIV-V-A004IPCAVD009
• Study Type: interventional
• Target: 393
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of this study is to assess the safety and tolerability of various regimens containing adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV), Modified Vaccinia Ankara (MVA)-Mosaic, and/or HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) components and to compare envelope binding antibody responses between the different vaccine regimens.

Conditions

Healthy

Keywords

Healthy; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome Virus; adenovirus serotype 26; Ad26.Mos.HIV; Modified Vaccinia Ankara; Glycoprotein; Adjuvant; Vaccine; Placebo

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Solicited Local Adverse Events (AEs) Post Vaccination

  Solicited local AEs (at injection site) included erythema, induration, swelling, itching and warmth were collected within 7 days after vaccination.

  Up to Week 49 (7 days post any dose)

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) Post Vaccination

  Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), headache, fatigue, myalgia, nausea, vomiting were collected within 7 days after vaccination.

  Up to Week 49 (7 days post any dose)

• Percentage of Participants With Unsolicited Adverse Events Post Vaccination

  Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.

  Up to Week 52 (28 days post vaccination)

• Number of Participants With Serious Adverse Events (SAEs) Post Vaccination

  An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study vaccine. An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product.

  Serious adverse events (SAEs) were reported up to Week 336 for Group 1 and 2 and up to Week 96 for the other groups (Group 3, 4, 5, 6, 7, and 8). Other adverse events (AEs) were reported for the main study period up to Week 96 for all the groups

• Percentage of Responders for Envelop (Env) Clade A, B and C-specific Binding Antibody Titers at Week 28

  The Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)- specific binding antibody titer were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (\>) lower limit of quantification (LLOQ) if baseline less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline greater than or equal to (\>=) LLOQ. The lower limits of quantification (LLOQs) for this assay were 625, 156.25, 625, and 156.25 endotoxin units per milliliter (EU/mL) for Clade A (92UG037.1), Clade B (1990a), Clade C (Con C), and Clade C (C97ZA.012) respectively.

  Week 28

Secondary Outcomes (6)

• Percentage of Responders for Clade C (C97ZA.012) Env Enzyme-linked Immunosorbent Assay (ELISA) Immunoglobulin G1 (IgG1), IgG2, IgG3 and IgG4 Glycoprotein (gp) 140 Binding Antibody

  Week 28, 52 and 96

• Percentage of Responders for Env ELISA Including Consensus C and Mos1 Antigens

  Week 28, 52 and 96

• Percentage of Responders for Env Antibody-dependent Cellular Phagocytosis (ADCP) gp Antibody

  Week 16, 26, 28, 52, 78, and 96

• Percentage of Responders for Human Immunodeficiency Virus Neutralizing Antibody (HIV nAb)

  Week 28 and 52

• Percentage of Responders for Binding Antibody Multiplex Assay (BAMA) IgG1-IgG4 and IgA and IgG-t Breadth Antibody

  Week 16, 28, 52, 78, and 96

Study Arms (8)

Group 1

EXPERIMENTAL

Participants will receive adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV) vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) vaccine containing 250 microgram (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: gp140 DP High-dose

Group 2

EXPERIMENTAL

Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + gp140 DP vaccine containing 50 mcg of total protein mixed with adjuvant at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: gp140 DP Low-dose

Group 3

EXPERIMENTAL

Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + placebo injection at Week 24 and 48.

Biological: Ad26.Mos.HIV; Drug: Placebo

Group 4

EXPERIMENTAL

Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by modified Vaccinia Ankara (MVA)-Mosaic vaccine + gp140 DP vaccine containing 250 mcg of total protein mixed with adjuvant at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: MVA-Mosaic; Biological: gp140 DP High-dose

Group 5

EXPERIMENTAL

Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + gp140 DP vaccine containing 50 mcg of total protein mixed with adjuvant at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: MVA-Mosaic; Biological: gp140 DP Low-dose

Group 6

EXPERIMENTAL

Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + placebo injection at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: MVA-Mosaic; Drug: Placebo

Group 7

EXPERIMENTAL

Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by gp140 DP vaccine containing 250 mcg of total protein mixed with adjuvant + placebo injection at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: gp140 DP High-dose; Drug: Placebo

Group 8

PLACEBO COMPARATOR

Participants will receive 1 placebo injection at Week 0 and 12; followed by 2 placebo injections at Week 24 and 48.

Drug: Placebo

Interventions

Ad26.Mos.HIV BIOLOGICAL

Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelop (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.

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6; Group 7

MVA-Mosaic BIOLOGICAL

Recombinant live attenuated MVA virus-vectored vaccine that has been genetically engineered to express 2 mosaic Gag, Pol, and Env sequences (Mosaic 1 and Mosaic 2). Total dose is 10\^8 plaque-forming unit per 0.5 mL injection administered intramuscularly.

Group 4; Group 5; Group 6

gp140 DP Low-dose BIOLOGICAL

The gp140 DP vaccine containing 50 mcg of total protein, mixed with aluminum phosphate adjuvant (0.425 mg aluminum), per 0.5 mL injection administered intramuscularly.

Group 2; Group 5

gp140 DP High-dose BIOLOGICAL

The gp140 DP vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.

Group 1; Group 4; Group 7

Placebo DRUG

Normal saline, 0.5 mL injection administered intramuscularly.

Group 3; Group 6; Group 7; Group 8

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be healthy on the basis of physical examination, medical history, electrocardiogram (ECG) and laboratory criteria, and vital signs measurement performed at Screening
• Participants are negative for human immunodeficiency virus (HIV) infection at Screening
• All female participants of childbearing potential must have a negative serum (beta human chorionic gonadotropin) at Screening, and a negative urine pregnancy test pre-dose on Week 0, 12, 24, and 48
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction until 3 months after receiving the last dose of study vaccine. A man must agree not to donate sperm until 3 months after receiving the last dose of study vaccine
• Participants are assessed by the clinic staff as being at low risk for HIV infection

You may not qualify if:

• Participant has chronic active hepatitis B or active hepatitis C, active syphilis infection, chlamydia, gonorrhea, or trichomonas. Active syphilis documented by exam or serology unless positive serology is due to past treated infection
• In the 12 months prior to enrollment, 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 any clinically significant acute or chronic medical condition that in the opinion of the investigator would preclude participation (for example, history of seizure disorders, bleeding/clotting disorder, autoimmune disease, active malignancy, poorly controlled asthma, active tuberculosis or other systemic infections)
• Participant has had major surgery within the 4 weeks prior to study entry or planned major surgery through the course of the study
• Participant has had a thyroidectomy, or thyroid disease requiring medication during the last 12 months
• Participant has a history of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow up)
• Participant has an ECG (per examination and interpretation of a cardiologist) with clinically significant findings, or features that would interfere with the assessment of myo/pericarditis, including any of the following: a) conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS \>=120 millisecond \[ms\], PR interval \>=220 ms, any 2nd or 3rd degree AV block, or QTc prolongation \[\>450 ms\]); b) significant repolarization (ST segment or T wave) abnormality; c) significant atrial or ventricular arrhythmia, frequent atrial or ventricular ectopy (for example frequent premature atrial contractions, 2 premature ventricular contractions in a row); d) ST elevation consistent with ischemia, or evidence of past or evolving myocardial infarction
• Participant has a history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, or neomycin or streptomycin or egg products

Sponsors & Collaborators

• Janssen Vaccines & Prevention B.V.: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• US Military HIV Research Program: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• International AIDS Vaccine Initiative: collaborator

Study Sites (12)

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Rockville, Maryland, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Austin, Texas, United States

Location

Unknown Facility

Kigali, Rwanda

Location

Unknown Facility

Cape Town, South Africa

Location

Unknown Facility

Durban, South Africa

Location

Unknown Facility

Johannesburg, South Africa

Location

Unknown Facility

Bangkok, Thailand

Location

Unknown Facility

Entebbe, Uganda

Location

Unknown Facility

Kampala, Uganda

Location

Related Publications (2)

• van Duijn J, Stieh D, Fernandez N, King D, Gilmour J, Tolboom J, Callewaert K, Willems W, Pau MG, De Rosa SC, McElrath MJ, Barouch DH, Hayes P. Mosaic HIV-1 vaccination induces anti-viral CD8+ T cell functionality in the phase 1/2a clinical trial APPROACH. J Virol. 2023 Oct 31;97(10):e0112623. doi: 10.1128/jvi.01126-23. Epub 2023 Oct 9.

  PMID: 37811993 DERIVED

• Barouch DH, Tomaka FL, Wegmann F, Stieh DJ, Alter G, Robb ML, Michael NL, Peter L, Nkolola JP, Borducchi EN, Chandrashekar A, Jetton D, Stephenson KE, Li W, Korber B, Tomaras GD, Montefiori DC, Gray G, Frahm N, McElrath MJ, Baden L, Johnson J, Hutter J, Swann E, Karita E, Kibuuka H, Mpendo J, Garrett N, Mngadi K, Chinyenze K, Priddy F, Lazarus E, Laher F, Nitayapan S, Pitisuttithum P, Bart S, Campbell T, Feldman R, Lucksinger G, Borremans C, Callewaert K, Roten R, Sadoff J, Scheppler L, Weijtens M, Feddes-de Boer K, van Manen D, Vreugdenhil J, Zahn R, Lavreys L, Nijs S, Tolboom J, Hendriks J, Euler Z, Pau MG, Schuitemaker H. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet. 2018 Jul 21;392(10143):232-243. doi: 10.1016/S0140-6736(18)31364-3. Epub 2018 Jul 6.

  PMID: 30047376 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Vaccines & Prevention B.V.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Vaccines & Prevention B.V. Clinical Trials

  Janssen Vaccines & Prevention B.V.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: December 12, 2014
• Study Start: December 22, 2014
• Primary Completion: August 29, 2017
• Study Completion: March 28, 2022
• Last Updated: February 4, 2025
• Results First Posted: November 4, 2020

Record last verified: 2025-01

Locations

RW (1); UG (2); US (5); TH (1); ZA (3)