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
Overview
- Phase
- Phase 1
- Intervention
- Ad26.Mos.HIV
- Conditions
- Healthy
- Sponsor
- Janssen Vaccines & Prevention B.V.
- Enrollment
- 393
- Primary Endpoint
- Percentage of Participants With Solicited Systemic Adverse Events (AEs) Post Vaccination
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
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
Arms & Interventions
Group 1
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.
Intervention: Ad26.Mos.HIV
Group 1
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.
Intervention: gp140 DP High-dose
Group 2
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.
Intervention: Ad26.Mos.HIV
Group 2
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.
Intervention: gp140 DP Low-dose
Group 3
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.
Intervention: Ad26.Mos.HIV
Group 3
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.
Intervention: Placebo
Group 4
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.
Intervention: Ad26.Mos.HIV
Group 4
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.
Intervention: MVA-Mosaic
Group 4
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.
Intervention: gp140 DP High-dose
Group 6
Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + placebo injection at Week 24 and 48.
Intervention: MVA-Mosaic
Group 5
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.
Intervention: Ad26.Mos.HIV
Group 5
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.
Intervention: MVA-Mosaic
Group 5
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.
Intervention: gp140 DP Low-dose
Group 6
Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + placebo injection at Week 24 and 48.
Intervention: Ad26.Mos.HIV
Group 6
Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + placebo injection at Week 24 and 48.
Intervention: Placebo
Group 7
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.
Intervention: Ad26.Mos.HIV
Group 7
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.
Intervention: gp140 DP High-dose
Group 7
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.
Intervention: Placebo
Group 8
Participants will receive 1 placebo injection at Week 0 and 12; followed by 2 placebo injections at Week 24 and 48.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Participants With Solicited Systemic Adverse Events (AEs) Post Vaccination
Time Frame: Up to Week 49 (7 days post any dose)
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.
Percentage of Participants With Solicited Local Adverse Events (AEs) Post Vaccination
Time Frame: Up to Week 49 (7 days post any dose)
Solicited local AEs (at injection site) included erythema, induration, swelling, itching and warmth were collected within 7 days after vaccination.
Percentage of Participants With Unsolicited Adverse Events Post Vaccination
Time Frame: Up to Week 52 (28 days post vaccination)
Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.
Number of Participants With Serious Adverse Events (SAEs) Post Vaccination
Time Frame: 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
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.
Percentage of Responders for Envelop (Env) Clade A, B and C-specific Binding Antibody Titers at Week 28
Time Frame: 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.
Secondary Outcomes
- 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 With Interferon-gamma (IFN-gamma) T Cell Responses Enzyme-linked Immunospot Assay (ELISpot)(Week 26, 50, 78 and 96)
- 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 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)