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

Study Overview
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Brief Summary
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The primary purpose of this study is to assess safety, tolerability of the different vaccine schedules (different regimen durations and different number of dose administrations) with Ad26.Mos.HIV and Clade C Glycoprotein (gp) 140 and to assess Envelope (Env)-binding Antibody (Ab) responses of the different vaccine schedules.

Detailed Description
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This is a phase 1 single-center, 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. Participants will be randomized in to 3 groups and will receive study vaccines or placebo. Group 1 will have 4 vaccination time points during 48 weeks, Groups 2 and 3 will have 3 vaccination time points during 24 weeks. The study comprises a Screening Period (up to 4 weeks), a Vaccination Period (maximum 48 weeks), and a Follow-up Period (up to 72 weeks). Participants' safety will be monitored throughout the study. An optional Long-term Extension (LTE) phase (approximately 1 year after Week 72) will be performed for participants randomized to receive study vaccine, who have received all planned vaccinations and are negative for HIV infection at Week 72. The duration of the participation will be approximately 124 weeks for participants participating to the optional LTE phase.

Official Title
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A Randomized, Parallel-group, Placebo-controlled, Double-blind Phase 1 Study in Healthy HIV-uninfected Adults to Evaluate Safety/Tolerability and Immunogenicity of Different Vaccine Schedules With Ad26.Mos.HIV and Clade C gp140

Conditions
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Healthy

Intervention / Treatment
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* Biological: Ad26.Mos.HIV
* Biological: Clade C gp140
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is voluntarily willing to participate in the study Participant must be healthy on the basis of physical examination, medical history, electrocardiogram (ECG), 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 pregnancy test (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 Exclusion Criteria: Participant has chronic hepatitis B or active hepatitis C, active syphilis infection, chlamydia, gonorrhea, or trichomonas . Active syphilis documented by serology unless positive serology is due to past treated infection In the 12 months prior to randomization, participant has a history of newly acquired herpes simplex virus type 2, syphilis, gonorrhea, non-gonococcal urethritis, chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments Participant has had major surgery within 4 weeks prior to Screening or planned major surgery through the course of the study Participant has had a thyroidectomy or active thyroid disease requiring medication during the last 12 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1A<br>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<br>* 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.<br>Biological: Clade C gp140<br>* The Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.<br>|
| Placebo Comparator: Group 1B<br>Participants will receive placebo at weeks 0, 12, 24 and 48. | Drug: Placebo<br>* Normal saline, 0.5 mL injection administered intramuscularly.<br>|
| Experimental: Group 2A<br>Participants will receive Ad26.Mos.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 mcg of total protein mixed with adjuvant (aluminum phosphate) at Week 0, 12 and 24. | Biological: Ad26.Mos.HIV<br>* 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.<br>Biological: Clade C gp140<br>* The Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.<br>|
| Placebo Comparator: Group 2B<br>Participants will receive placebo at weeks 0, 12 and 24. | Drug: Placebo<br>* Normal saline, 0.5 mL injection administered intramuscularly.<br>|
| Experimental: Group 3A<br>Participants will receive Ad26.Mos.HIV vaccine at Week 0; followed by Ad26.Mos.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 mcg of total protein mixed with adjuvant (aluminum phosphate) at Week 8 and 24. | Biological: Ad26.Mos.HIV<br>* 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.<br>Biological: Clade C gp140<br>* The Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.<br>|
| Placebo Comparator: Group 3B<br>Participants will receive placebo at weeks 0, 8 and 24. | Drug: Placebo<br>* Normal saline, 0.5 mL injection administered intramuscularly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titer to HIV-Envelope Specific Binding Antibodies Assessed by Env-Ab-binding Assay |  | Up to Week 72 | 
| Breadth of HIV-Envelope Specific Binding Antibodies Assessed by Env-Ab-binding Assay |  | Up to Week 72 | 
| Number of Participants With Local and Systemic Reactogenicity for 8 Days After Each Vaccination | Participants will be asked to note occurrences of local reactions: pain/tenderness, erythema or swelling/induration at the injection site, and systemic events: fever (temperature measurement), fatigue, headache, nausea, myalgia and chills daily for 8 days post-vaccination. These occurrences will be recorded through the diary card provided to serve as a reminder to the participants for the next clinic visit. | Up to 8 days after each vaccination | 
| Treatment Emergent Adverse Events (AEs) |  | Up to Week 72 | 
| Serious Adverse Events (SAEs) and AEs of Special Interest (AESI) |  | Up to Week 124 | 
| Discontinuations From Vaccination or From Study due to AEs |  | At the time of discontinuation from vaccination or from study (Up to Week 72) | 
| Number of Participants With AEs or SAEs |  | Up to 28 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Env-Specific Functional Antibodies: Phagocytosis Score |  | Up to Week 72 | 
| Env-Specific Functional Antibodies: Breadths |  | Up to Week 72 | 
| Env-Specific Binding Antibody Isotypes: Titers | The Isotyping (Clade C) (IgA, IgG1-4)- Env binding antibody titers will be assessed using ELISA. | Up to Week 72 | 
| Env-Specific Binding Antibody Isotypes: Breadths | The Isotyping (Clade C) (IgA, IgG1-4)- Env binding antibody breadths will be assessed using ELISA. | Up to Week 72 | 
| Env-Specific Neutralizing Antibodies (nAbs): Titers |  | Up to Week 72 | 
| Env-Specific Neutralizing Antibodies (nAbs): Breadths |  | Up to Week 72 | 
| Induction of New T-cell Immune Response by the Vaccine | Induction of new T-cell immune response against one or more of the vaccine epitopes using Interferon gamma Enzyme Linked Immuno spot assay (IFNg-ELISPOT assay) measuring Spot forming Units per 1 million peripheral blood mononuclear cells (SFU/1 mio PBMCs) above threshold (> 50 sfu/mio PBMC). | Up to Week 72 | 
| Change From Baseline of the Frequency of HIV-Specific PBMC and/or CD4 and/or CD8 T cells as Measured by ELISpot Interferon (IFN) Gamma |  | Up to Week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Human Immunodeficiency Virus, adenovirus serotype 26, Ad26.Mos.HIV, Vaccine, Placebo, Glycoprotein, IPCAVD010