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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: Ad26.Mos.HIV; Biological: Clade C gp140; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1A; 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; 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.; Biological: Clade C gp140; The Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Placebo Comparator: Group 1B; Participants will receive placebo at weeks 0, 12, 24 and 48.	Drug: Placebo; Normal saline, 0.5 mL injection administered intramuscularly.
Experimental: Group 2A; 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; 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.; Biological: Clade C gp140; The Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Placebo Comparator: Group 2B; Participants will receive placebo at weeks 0, 12 and 24.	Drug: Placebo; Normal saline, 0.5 mL injection administered intramuscularly.
Experimental: Group 3A; 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; 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.; Biological: Clade C gp140; The Clade C gp140 vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
Placebo Comparator: Group 3B; Participants will receive placebo at weeks 0, 8 and 24.	Drug: Placebo; Normal saline, 0.5 mL injection administered intramuscularly.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mucosal Immunogenicity	Immune Responses to the Different Vaccine Schedules in Mucosal Secretions.	Up to week 72

Collaborators and Investigators

• Sponsor: Janssen Vaccines & Prevention B.V.

Publications and helpful links

General Publications

• Stephenson KE, Wegmann F, Tomaka F, Walsh SR, Tan CS, Lavreys L, Ansel JL, Kanjilal DG, Jaegle K, Nkolola JP, Peter L, Fogel R, Bradshaw C, Tyler A, Makoni T, Howe L, Quijada D, Chandrashekar A, Bondzie EA, Borducchi EN, Yanosick KE, Hendriks J, Nijs S, Truyers C, Tolboom J, Zahn RC, Seaman MS, Alter G, Stieh DJ, Pau MG, Schuitemaker H, Barouch DH. Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). Lancet HIV. 2020 Jun;7(6):e410-e421. doi: 10.1016/S2352-3018(20)30001-1. Epub 2020 Feb 17. Erratum In: Lancet HIV. 2020 Feb 28;:

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2016
• Primary Completion (Actual): January 5, 2018
• Study Completion (Actual): January 3, 2019

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: February 12, 2016
• First Posted (Estimate): February 18, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Vaccine; Healthy; Human Immunodeficiency Virus; Placebo; Glycoprotein; adenovirus serotype 26; Ad26.Mos.HIV; IPCAVD010
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: CR108068; VAC89220HPX1002 (Other Identifier: Janssen Vaccines & Prevention B.V.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No