Clinical trial NCT02315703: 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
Official title: A Phase 1/2a Trial to Evaluate the Safety/Tolerability and Immunogenicity of Homologous Ad26 Mosaic Vector Regimens or Ad26 Mosaic and MVA Mosaic Heterologous Vector Regimens, With High-Dose, Low-Dose or no Clade C gp140 Protein Plus Adjuvant for HIV Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: US Military HIV Research Program
name: Beth Israel Deaconess Medical Center
name: International AIDS Vaccine Initiative
First posted: 2014-12-12
Enrollment: 393
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: This is a multicenter (more than 1 hospital or medical school team work on a study), randomized (the study drug is assigned by chance), parallel group (each group of participants will be treated at the same time), placebo-controlled (study in which the experimental treatment or procedure is compared to a pretend treatment with no drug in it to test if the drug has a real effect), and double-blind (neither physician nor participant knows the treatment that the participant receives) study. All eligible participants will be randomly assigned to receive 1 of the 8 vaccine regimens. Participants will receive study vaccines (Ad26.Mos.HIV, MVA-Mosaic, gp140 DP, and placebo) 4 times as per assigned regimen. The study comprises a Screening Period (up to 4 weeks), a Vaccination Period (participants will be vaccinated at Baseline (Week 0), Week 12, Week 24 and Week 48), and a Follow-up Period (up to 48 weeks). A long-term follow-up period (approximately 2 years after Week 96) will continue for participants randomized to the regimen subsequently selected for future studies, based on analysis of Week 28 data. If Week 28 data are inconclusive, Week 52 data will be considered for regimen selection. If no clear decision can be made, the extended follow-up period could include participants from more than 1 group for assessing durability of immune responses. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants With Solicited Local Adverse Events (AEs) Post Vaccination
timeFrame: Up to Week 49 (7 days post any dose)
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) Post Vaccination
timeFrame: Up to Week 49 (7 days post any dose)
measure: Percentage of Participants With Unsolicited Adverse Events Post Vaccination
timeFrame: Up to Week 52 (28 days post vaccination)
measure: Number of Participants With Serious Adverse Events (SAEs) Post Vaccination
timeFrame: 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
measure: Percentage of Responders for Envelop (Env) Clade A, B and C-specific Binding Antibody Titers at Week 28
timeFrame: Week 28
Secondary outcomes:
measure: 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
timeFrame: Week 28, 52 and 96
measure: Percentage of Responders for Env ELISA Including Consensus C and Mos1 Antigens
timeFrame: Week 28, 52 and 96
measure: Percentage of Responders for Env Antibody-dependent Cellular Phagocytosis (ADCP) gp Antibody
timeFrame: Week 16, 26, 28, 52, 78, and 96
measure: Percentage of Responders for Human Immunodeficiency Virus Neutralizing Antibody (HIV nAb)
timeFrame: Week 28 and 52
measure: Percentage of Responders for Binding Antibody Multiplex Assay (BAMA) IgG1-IgG4 and IgA and IgG-t Breadth Antibody
timeFrame: Week 16, 28, 52, 78, and 96
measure: Percentage of Responders With Interferon-gamma (IFN-gamma) T Cell Responses Enzyme-linked Immunospot Assay (ELISpot)
timeFrame: Week 26, 50, 78 and 96
Other outcomes:
Locations:
city: Aurora
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Rockville
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Austin
country: United States
state: Texas
city: Kigali
country: Rwanda
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Johannesburg
country: South Africa
city: Bangkok
country: Thailand
city: Entebbe
country: Uganda
city: Kampala
country: Uganda
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.