Evaluating the Safety and Immunogenicity of a Prime-boost Vaccine Regimen of GEO-D02 DNA and MVA/HIV62B With and Without B63521^11 gp120 and IHV01 gp120 Env Proteins in Healthy, HIV-uninfected Adult Participants
- Conditions
- HIV Infections
- Interventions
- Biological: GEO-D02 DNABiological: MVA/HIV62B VaccineBiological: IHV01 ProteinBiological: B63521^11 gp120Biological: Protein Placebo
- Registration Number
- NCT04041674
- Brief Summary
The purpose of this study is to evaluate the safety and immunogenicity of a prime-boost vaccine regimen of GEO-D02 DNA and MVA/HIV62B with and without B63521\^11 gp120 and IHV01 gp120 Env proteins in healthy, HIV-uninfected adult participants.
- Detailed Description
This study will evaluate the safety and immunogenicity of a prime-boost vaccine regimen of GEO-D02 DNA and MVA/HIV62B with and without B63521\^11 gp120 and IHV01 gp120 Env proteins in healthy, HIV-uninfected adult participants.
Participants will be randomly assigned to one of five groups. Participants in all five groups will receive GEO-D02 DNA by intramuscular (IM) injection at Months 0 and 2. Then, at Months 4, 6, and 10, participants will receive three additional injections according to their assigned group:
* Group 1: MVA/HIV62B, placebo for B63521\^11 gp120, and placebo for IHV01, all by IM injection
* Group 2: MVA/HIV62B by IM injection and placebo for B63521\^11 gp120 and for IHV01, both by subcutaneous (SC) injection
* Group 3: MVA/HIV62B, B63521\^11 gp120, and IHV01, all by IM injection
* Group 4: MVA/HIV62B, placebo for B63521\^11 gp120, and IHV01, all by IM injection
* Group 5: MVA/HIV62B by IM injection and IHV01 and B63521\^11 gp120, both by SC injection
Participants will attend several study visits through Month 16. Visits may include physical examinations, blood and urine collection, electrocardiogram, HIV testing, risk reduction counseling, and questionnaires. Study staff will contact participants at Month 24 for follow-up health monitoring.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 3 (T2): DNA + MVA + IHV01 + B63 MVA/HIV62B Vaccine Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus 150 mcg of B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 4 (T3): DNA + MVA +IHV01 + Placebo IHV01 Protein Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus placebo for B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 5 (T4): DNA + MVA +IHV01 (SC)+ B63 (SC) MVA/HIV62B Vaccine Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 3. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus 150 mcg of B63521\^11 gp120 by SC injection plus 150 mcg of IHV01 by SC injection at Months 4, 6, and 10. Group 1 (T1): DNA + MVA + Placebo (IM) MVA/HIV62B Vaccine Participants will receive 3 mg of GEO-D02 DNA by intramuscular (IM) injection at Months 0 and 2. Participants will also receive 1×10\^8 50% tissue culture infective dose (TCID50) of MVA/HIV62B plus placebo for B63521\^11 gp120 plus placebo for IHV01, each by IM injection at Months 4, 6, and 10. Group 3 (T2): DNA + MVA + IHV01 + B63 B63521^11 gp120 Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus 150 mcg of B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 2 (T1): DNA + MVA + Placebo (SC) GEO-D02 DNA Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus placebo for B63521\^11 gp120 by subcutaneous (SC) injection plus placebo for IHV01 by SC injection at Months 4, 6, and 10. Group 2 (T1): DNA + MVA + Placebo (SC) MVA/HIV62B Vaccine Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus placebo for B63521\^11 gp120 by subcutaneous (SC) injection plus placebo for IHV01 by SC injection at Months 4, 6, and 10. Group 1 (T1): DNA + MVA + Placebo (IM) GEO-D02 DNA Participants will receive 3 mg of GEO-D02 DNA by intramuscular (IM) injection at Months 0 and 2. Participants will also receive 1×10\^8 50% tissue culture infective dose (TCID50) of MVA/HIV62B plus placebo for B63521\^11 gp120 plus placebo for IHV01, each by IM injection at Months 4, 6, and 10. Group 5 (T4): DNA + MVA +IHV01 (SC)+ B63 (SC) GEO-D02 DNA Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 3. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus 150 mcg of B63521\^11 gp120 by SC injection plus 150 mcg of IHV01 by SC injection at Months 4, 6, and 10. Group 1 (T1): DNA + MVA + Placebo (IM) Protein Placebo Participants will receive 3 mg of GEO-D02 DNA by intramuscular (IM) injection at Months 0 and 2. Participants will also receive 1×10\^8 50% tissue culture infective dose (TCID50) of MVA/HIV62B plus placebo for B63521\^11 gp120 plus placebo for IHV01, each by IM injection at Months 4, 6, and 10. Group 4 (T3): DNA + MVA +IHV01 + Placebo Protein Placebo Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus placebo for B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 2 (T1): DNA + MVA + Placebo (SC) Protein Placebo Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus placebo for B63521\^11 gp120 by subcutaneous (SC) injection plus placebo for IHV01 by SC injection at Months 4, 6, and 10. Group 3 (T2): DNA + MVA + IHV01 + B63 GEO-D02 DNA Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus 150 mcg of B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 3 (T2): DNA + MVA + IHV01 + B63 IHV01 Protein Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus 150 mcg of B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 4 (T3): DNA + MVA +IHV01 + Placebo GEO-D02 DNA Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus placebo for B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 4 (T3): DNA + MVA +IHV01 + Placebo MVA/HIV62B Vaccine Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 2. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B plus placebo for B63521\^11 gp120 plus 150 mcg of IHV01, each by IM injection at Months 4, 6, and 10. Group 5 (T4): DNA + MVA +IHV01 (SC)+ B63 (SC) IHV01 Protein Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 3. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus 150 mcg of B63521\^11 gp120 by SC injection plus 150 mcg of IHV01 by SC injection at Months 4, 6, and 10. Group 5 (T4): DNA + MVA +IHV01 (SC)+ B63 (SC) B63521^11 gp120 Participants will receive 3 mg of GEO-D02 DNA by IM injection at Months 0 and 3. Participants will also receive 1×10\^8 TCID50 of MVA/HIV62B by IM injection plus 150 mcg of B63521\^11 gp120 by SC injection plus 150 mcg of IHV01 by SC injection at Months 4, 6, and 10.
- Primary Outcome Measures
Name Time Method Frequency of serious adverse events Measured through Month 16 Summarized using MedDRA System Organ Class and preferred terms
HIV-specific IgG binding breadth to cross-clade panels of gp120 and V1V2, and gp41 Measured through Month 10.5 As assessed by BAMA
Response rate of CD4+ T-cell responses to Env Measured through Month 10.5 As assessed by intracellular cytokine staining (ICS)
Frequency of systemic reactogenicity signs and symptoms Measured through Month 10 Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, and nausea.
HIV-specific IgG binding magnitude to cross-clade panels of gp120 and V1V2, and gp41 Measured through Month 10.5 As assessed by binding antibody multiplex assay (BAMA)
HIV-specific IgG binding response rate to cross-clade panels of gp120 and V1V2, and gp41 Measured through Month 10.5 As assessed by BAMA
Magnitude of CD4+ T-cell responses to Env Measured through Month 10.5 As assessed by ICS
Frequency of local reactogenicity signs and symptoms Measured through Month 10 Local symptoms include pain and/or tenderness at the injection site.
Frequency of adverse events Measured through Month 16 Summarized using Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and preferred terms
- Secondary Outcome Measures
Name Time Method IgA responses to gp120 and gp41 Measured through Month 16 As assessed by BAMA
IgG avidity to defined epitope specificities Measured through Month 10.5 Determined from the immunogenicity data
HIV-specific IgG binding magnitude to gp120, V1V2, and gp41 Measured through Month 16 As assessed by BAMA
Response rate of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibody responses Measured through Month 16 Assessed using serum samples taken at a primary immunogenicity timepoint
HIV-specific IgG binding magnitude to V3, CD4i and gp41 IDR Measured through Month 10.5 As assessed by BAMA
IgA responses to gp120, V1V2, and gp41 Measured through Month 10.5 As assessed by BAMA
IgG3 responses to gp120, V1V2, and gp41 Measured through Month 10.5 As assessed by BAMA
HIV-specific IgG binding response rate to V3, CD4i and gp41 IDR Measured through Month 10.5 As assessed by BAMA
HIV-specific IgG binding response rate to gp120, V1V2, and gp41 Measured through Month 16 As assessed by BAMA
Magnitude of antibody-dependent cellular phagocytosis (ADCP)-mediating antibody responses Measured through Month 16 Measured using serum samples taken at baseline and at a primary immunogenicity timepoint
IgG3 responses to gp120 and gp41 Measured through Month 16 As assessed by BAMA
Magnitude of ADCC-mediating antibody responses Measured through Month 16 Assessed using serum samples taken at a primary immunogenicity timepoint
Response rate of vaccine-elicited antibody binding to FcƴR proteins Measured through Month 16 Assessed on serum samples taken at the primary immunogenicity timepoints and baseline
Magnitude of vaccine-elicited antibody binding to FcƴR proteins Measured through Month 16 Assessed on serum samples taken at the primary immunogenicity timepoints and baseline
Response rate of antibody-dependent cellular phagocytosis (ADCP)-mediating antibody responses Measured through Month 16 Measured using serum samples taken at baseline and at a primary immunogenicity timepoint