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A Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With Modified Vaccinia Ankara (MVA)-Mosaic OR Ad26.Mos4.HIV Plus a Combination of Mosaic and Clade C gp140 Protein in Human Immunodeficiency Virus (HIV) Type 1 Infected Adults on Suppressive Antiretroviral Treatment

Primary Purpose

Human Immunodeficiency Virus

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ad26.Mos4.HIV
MVA-Mosaic
Clade C gp140 + Mosaic gp140
Placebo
Sponsored by
Janssen Vaccines & Prevention B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Human Immunodeficiency Virus

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Each participant must have documented Human immunodeficiency virus type1 (HIV-1) infection
  • Each participant must be on suppressive antiretroviral treatment (ART) for at least 48 weeks prior to randomization and on stable suppressive ART for at least 4 weeks prior to screening. Changes in antiretrovirals (ARVs) can be made for safety/tolerability reasons only until 4 weeks prior to screening
  • Each participant must have started ART outside of the acute or early phase of infection
  • Each participant must have a plasma HIV ribonucleic acid (RNA) less than (<) 50 copies/ milliliter (mL) at screening and at least one documented evidence of plasma HIV RNA <50 copies/mL after the last ART change. In case of ART change within the 48 weeks prior randomization, at least one additional more recent documented plasma HIV RNA <50 copies/mL is required. One blip of HIV RNA greater than (>)50 and <200 copies/mL within 24 weeks prior to screening is acceptable, provided that the 2 most recent (after last ART change, tested before and/or during screening) HIV RNA results are <50 copies/mL
  • Each participant must be medically stable as confirmed by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening

Exclusion Criteria:

  • Anyone who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study, or within 3 months after the last vaccination
  • Anyone with contraindication to intramuscular injections and blood draws example, bleeding disorders
  • Anyone with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0ºC (degree centigrade) within 24 hours prior to the first dose of study vaccine; enrollment at a later date is permitted
  • Anyone with a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
  • Anyone with a history of an underlying clinically significant acute or uncontrolled chronic medical condition or physical examination findings 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
  • Anyone with a history of Acquired Immunodeficiency Syndrome (AIDS)-defining illness according to Centers for Disease Control and prevention (CDC) criteria based on available medical history and assessed by the investigator as clinically relevant. A case summary for every participant with AIDS-defining illnesses assessed by the investigator as clinically irrelevant must be provided to the sponsor and Protocol Safety Review Team (PSRT), who will determine eligibility on a case-by-case basis prior to randomization
  • Anyone with a history of CD4+ less than (<) 200 cells per millimeter cube (cells/mm^3), based on available medical history and assessed by the investigator as clinically relevant. A case summary for every participant with history of CD4+ <200 cells/mm^3 assessed by the investigator as clinically irrelevant must be provided to the sponsor and PSRT, who will determine eligibility on a case-by-case basis prior to randomization
  • Anyone with chronic active hepatitis B (measured by hepatitis B surface antigen test) or active hepatitis C (measured by hepatitis C virus [HCV] antibody test; if positive, HCV RNA polymerase chain reaction test will be used to confirm active versus past HCV infection) or syphilis infection that has not been effectively treated. Positive syphilis serology due to past effectively treated infection is not exclusionary
  • Anyone who received or plans to receive: a) licensed live attenuated vaccines within 28 days before or after planned administration of any of the study vaccinations; b) other licensed (not live) vaccines - within 14 days before or after planned administration of any of the study vaccinations
  • Anyone who received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of the first dose of study vaccine. Receipt of prophylactic or therapeutic HIV vaccine candidate at any time is always exclusionary. Exceptions: Participants can be included where the vaccine received was subsequently licensed. Participants with proof of having received only a placebo vaccine can also be included

Sites / Locations

  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Group 1: Ad26.Mos4.HIV + MVA-Mosaic/Placebo

Group 2: Ad26.Mos4.HIV + Clade C gp140 + Mosaic gp140

Group 3: Placebo

Arm Description

Participants will receive adenovirus serotype 26-Mosaic 4 -Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5*10^10 virus particles (vp) as intramuscular (IM) injection at Weeks 0 and 12 (1 injection) followed by modified Vaccinia Ankara-Mosaic (MVA-Mosaic) 10^8 Plaque-forming unit (pfu) and placebo as IM injection at Weeks 24 and 36 (2 injections).

Participants will receive Ad26.Mos4.HIV, 5*10^10 vp as IM injection at Weeks 0 and 12 (1 injection) followed by both Ad26.Mos4.HIV 5*10^10 vp plus Clade C gp140 (125 microgram [mcg]) plus Mosaic gp140 (125 mcg) with aluminum phosphate adjuvant or an equivalent dose of a bivalent vaccine that includes both Clade C gp140 and Mosaic gp140, and aluminum phosphate adjuvant in a single vial, via IM injection at Weeks 24 and 36 (2 injections).

Participants will receive 0.9 percent (%) saline as IM injection at Weeks 0, 12 (one injection) and at Week 24, 36 (two injections).

Outcomes

Primary Outcome Measures

Percentage of Participants With Solicited Local Adverse Events (AEs) as a Measure of Safety and Tolerability
Solicited local AEs: erythema, swelling/induration, and pain/tenderness will be assessed.
Percentage of Participants With Solicited Systemic AEs as a Measure of Safety and Tolerability
Solicited systemic AEs: fever (temperature measurement), fatigue, headache, nausea, myalgia, and chills will be assessed.
Percentage of Participants With AEs as a Measure of Safety and Tolerability
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Secondary Outcome Measures

Total IgG and Subclass Specific Antibody Titer
Total immunoglobulin G (IgG) and subclass (IgG1-4) specific antibody titers (binding antibody) to envelope (Env) proteins representing Clades A, B, and C, as well as Mosaic antigens.
Antibody Functionality Assessment by Antibody-dependent Cell-mediated Phagocytosis (ADCP)
Antibody functionality assessment will be assessed by antibody-dependent cell-mediated phagocytosis (ADCP) assay.
Magnitude of T-cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay
Intracellular cytokine staining (ICS) assays with Env, group-specific antigen (Gag), and/or polymerase (Pol)-peptide pools will be used to determine the magnitude of T-cell responses elicited.
Functionality of T-cell Responses as Measured by ICS Assay
ICS assays with Env, Gag, and/or Pol-peptide pools will be used to determine the functionality of T-cell responses elicited.
Phenotype of T-cell Responses as Measured by ICS Assay
ICS assays with Env, Gag, and/or Pol-peptide pools will be used to determine the phenotype of T-cell responses elicited.
Frequency of Epitope Recognition by Enzyme-Linked Immunospot (ELISPOT)
Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme linked immunospot assay (ELISPOT).

Full Information

First Posted
September 25, 2017
Last Updated
February 7, 2022
Sponsor
Janssen Vaccines & Prevention B.V.
Collaborators
Beth Israel Deaconess Medical Center, Ragon Institute of MGH, MIT and Harvard, US Military HIV Research Program
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1. Study Identification

Unique Protocol Identification Number
NCT03307915
Brief Title
A Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With Modified Vaccinia Ankara (MVA)-Mosaic OR Ad26.Mos4.HIV Plus a Combination of Mosaic and Clade C gp140 Protein in Human Immunodeficiency Virus (HIV) Type 1 Infected Adults on Suppressive Antiretroviral Treatment
Official Title
A Safety, Tolerability and Immunogenicity Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With MVA-Mosaic OR Ad26.Mos4.HIV Plus a Combination of Mosaic and Clade C gp140 Protein in HIV-1 Infected Adults on Suppressive ART
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
March 5, 2018 (Actual)
Primary Completion Date
November 5, 2021 (Actual)
Study Completion Date
November 5, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Vaccines & Prevention B.V.
Collaborators
Beth Israel Deaconess Medical Center, Ragon Institute of MGH, MIT and Harvard, US Military HIV Research Program

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of this study is to assess safety/tolerability of 2 different prime/boost regimens containing adenovirus serotype 26 (Ad26).Mos4.HIV, Modified Vaccinia Ankara (MVA) -Mosaic or adjuvanted Mosaic and Clade C gp140 in Human immunodeficiency virus type 1 (HIV-1)-infected participants on suppressive antiretroviral treatment (ART).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Ad26.Mos4.HIV + MVA-Mosaic/Placebo
Arm Type
Experimental
Arm Description
Participants will receive adenovirus serotype 26-Mosaic 4 -Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5*10^10 virus particles (vp) as intramuscular (IM) injection at Weeks 0 and 12 (1 injection) followed by modified Vaccinia Ankara-Mosaic (MVA-Mosaic) 10^8 Plaque-forming unit (pfu) and placebo as IM injection at Weeks 24 and 36 (2 injections).
Arm Title
Group 2: Ad26.Mos4.HIV + Clade C gp140 + Mosaic gp140
Arm Type
Experimental
Arm Description
Participants will receive Ad26.Mos4.HIV, 5*10^10 vp as IM injection at Weeks 0 and 12 (1 injection) followed by both Ad26.Mos4.HIV 5*10^10 vp plus Clade C gp140 (125 microgram [mcg]) plus Mosaic gp140 (125 mcg) with aluminum phosphate adjuvant or an equivalent dose of a bivalent vaccine that includes both Clade C gp140 and Mosaic gp140, and aluminum phosphate adjuvant in a single vial, via IM injection at Weeks 24 and 36 (2 injections).
Arm Title
Group 3: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive 0.9 percent (%) saline as IM injection at Weeks 0, 12 (one injection) and at Week 24, 36 (two injections).
Intervention Type
Biological
Intervention Name(s)
Ad26.Mos4.HIV
Intervention Description
Participants will receive Ad26.Mos4.HIV 5*10^10 vp as 0.5 mL IM injection at Weeks 0, 12 in Group 1 and at Weeks 0, 12, 24, 36 in Group 2.
Intervention Type
Biological
Intervention Name(s)
MVA-Mosaic
Intervention Description
Participants will receive MVA-Mosaic 10^8 pfu as IM injection at Weeks 24 and 36.
Intervention Type
Biological
Intervention Name(s)
Clade C gp140 + Mosaic gp140
Intervention Description
Participants will receive both Clade C gp140 125 mcg plus Mosaic gp140 125 mcg (250 mcg coformulated with Aluminum phosphate adjuvant) OR an equivalent dose of a bivalent vaccine that includes both Clade C gp140 and Mosaic gp140, and aluminum phosphate adjuvant in a single vial, via IM injection at Weeks 24 and 36.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching placebo as IM injection at Weeks 24, 36 in Group 1 and at Weeks 0, 12, 24, 36 in Group 3.
Primary Outcome Measure Information:
Title
Percentage of Participants With Solicited Local Adverse Events (AEs) as a Measure of Safety and Tolerability
Description
Solicited local AEs: erythema, swelling/induration, and pain/tenderness will be assessed.
Time Frame
7 days post-vaccination (approximately up to 37 weeks)
Title
Percentage of Participants With Solicited Systemic AEs as a Measure of Safety and Tolerability
Description
Solicited systemic AEs: fever (temperature measurement), fatigue, headache, nausea, myalgia, and chills will be assessed.
Time Frame
7 days post-vaccination (approximately up to 37 weeks)
Title
Percentage of Participants With AEs as a Measure of Safety and Tolerability
Description
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time Frame
Approximately up to 96 weeks
Secondary Outcome Measure Information:
Title
Total IgG and Subclass Specific Antibody Titer
Description
Total immunoglobulin G (IgG) and subclass (IgG1-4) specific antibody titers (binding antibody) to envelope (Env) proteins representing Clades A, B, and C, as well as Mosaic antigens.
Time Frame
Up to post-vaccination follow-up period until Week 96
Title
Antibody Functionality Assessment by Antibody-dependent Cell-mediated Phagocytosis (ADCP)
Description
Antibody functionality assessment will be assessed by antibody-dependent cell-mediated phagocytosis (ADCP) assay.
Time Frame
Up to post-vaccination follow-up period until Week 96
Title
Magnitude of T-cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay
Description
Intracellular cytokine staining (ICS) assays with Env, group-specific antigen (Gag), and/or polymerase (Pol)-peptide pools will be used to determine the magnitude of T-cell responses elicited.
Time Frame
Up to post-vaccination follow-up period until Week 96
Title
Functionality of T-cell Responses as Measured by ICS Assay
Description
ICS assays with Env, Gag, and/or Pol-peptide pools will be used to determine the functionality of T-cell responses elicited.
Time Frame
Up to post-vaccination follow-up period until Week 96
Title
Phenotype of T-cell Responses as Measured by ICS Assay
Description
ICS assays with Env, Gag, and/or Pol-peptide pools will be used to determine the phenotype of T-cell responses elicited.
Time Frame
Up to post-vaccination follow-up period until Week 96
Title
Frequency of Epitope Recognition by Enzyme-Linked Immunospot (ELISPOT)
Description
Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme linked immunospot assay (ELISPOT).
Time Frame
Up to post-vaccination follow-up period until Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Each participant must have documented Human immunodeficiency virus type1 (HIV-1) infection Each participant must be on suppressive antiretroviral treatment (ART) for at least 48 weeks prior to randomization and on stable suppressive ART for at least 4 weeks prior to screening. Changes in antiretrovirals (ARVs) can be made for safety/tolerability reasons only until 4 weeks prior to screening Each participant must have started ART outside of the acute or early phase of infection Each participant must have a plasma HIV ribonucleic acid (RNA) less than (<) 50 copies/ milliliter (mL) at screening and at least one documented evidence of plasma HIV RNA <50 copies/mL after the last ART change. In case of ART change within the 48 weeks prior randomization, at least one additional more recent documented plasma HIV RNA <50 copies/mL is required. One blip of HIV RNA greater than (>)50 and <200 copies/mL within 24 weeks prior to screening is acceptable, provided that the 2 most recent (after last ART change, tested before and/or during screening) HIV RNA results are <50 copies/mL Each participant must be medically stable as confirmed by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening Exclusion Criteria: Anyone who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study, or within 3 months after the last vaccination Anyone with contraindication to intramuscular injections and blood draws example, bleeding disorders Anyone with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0ºC (degree centigrade) within 24 hours prior to the first dose of study vaccine; enrollment at a later date is permitted Anyone with a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Anyone with a history of an underlying clinically significant acute or uncontrolled chronic medical condition or physical examination findings 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 Anyone with a history of Acquired Immunodeficiency Syndrome (AIDS)-defining illness according to Centers for Disease Control and prevention (CDC) criteria based on available medical history and assessed by the investigator as clinically relevant. A case summary for every participant with AIDS-defining illnesses assessed by the investigator as clinically irrelevant must be provided to the sponsor and Protocol Safety Review Team (PSRT), who will determine eligibility on a case-by-case basis prior to randomization Anyone with a history of CD4+ less than (<) 200 cells per millimeter cube (cells/mm^3), based on available medical history and assessed by the investigator as clinically relevant. A case summary for every participant with history of CD4+ <200 cells/mm^3 assessed by the investigator as clinically irrelevant must be provided to the sponsor and PSRT, who will determine eligibility on a case-by-case basis prior to randomization Anyone with chronic active hepatitis B (measured by hepatitis B surface antigen test) or active hepatitis C (measured by hepatitis C virus [HCV] antibody test; if positive, HCV RNA polymerase chain reaction test will be used to confirm active versus past HCV infection) or syphilis infection that has not been effectively treated. Positive syphilis serology due to past effectively treated infection is not exclusionary Anyone who received or plans to receive: a) licensed live attenuated vaccines within 28 days before or after planned administration of any of the study vaccinations; b) other licensed (not live) vaccines - within 14 days before or after planned administration of any of the study vaccinations Anyone who received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of the first dose of study vaccine. Receipt of prophylactic or therapeutic HIV vaccine candidate at any time is always exclusionary. Exceptions: Participants can be included where the vaccine received was subsequently licensed. Participants with proof of having received only a placebo vaccine can also be included
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Vaccines & Prevention B.V. Clinical Trial
Organizational Affiliation
Janssen Vaccines & Prevention B.V.
Official's Role
Study Director
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With Modified Vaccinia Ankara (MVA)-Mosaic OR Ad26.Mos4.HIV Plus a Combination of Mosaic and Clade C gp140 Protein in Human Immunodeficiency Virus (HIV) Type 1 Infected Adults on Suppressive Antiretroviral Treatment

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