A Safety and Immunogenicity Study of a Plasmid DNA Prime and MVA Boost Vaccine in HIV-1 Infected Adults on ART
Primary Purpose
HIV-1 Infection
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
JS7 plasmid DNA and MVA62B vaccine
Sponsored by
About this trial
This is an interventional treatment trial for HIV-1 Infection focused on measuring Therapy for HIV Infection, Suppressive ART with no failures, Treatment interruption
Eligibility Criteria
Inclusion Criteria:
- Age 18-50 yrs.
- ART started within 18 mo. of last documented negative HIV Ab test, or within 13 mo. of last negative detuned HIV-1 Ab assay, or within 18 mo. of evolution of Western blot from indeterminate to positive in the presence of a positive Ab test
- No changes to ART treatment within 4 wks. of study entry
- Documentation of level of plasma HIV-1 RNA and CD4+ counts prior to ART
- On stable suppressive ART [HIV-1 RNA < 50 copies/mL (PCR) or < 75 copies/mL (bDNA) for at least 6 mo. prior to starting vaccination]
- No history of virologic failure
- CD4+ > 500 cells/µL
- Nadir CD4+ > 350 cells/µL unless measured in the setting of acute infection
Laboratory values:
- Hemoglobin ≥ 10g/dL (male) or 9g/dL (women)
- ANC > 1000 cells/µL
- ALT, AST ≤ 2.5 ULN
- Total bilirubin < 1.5 x ULN (≤ 5 x ULN on atazanavir)
- Fasting glucose ≤ 125 mg/dL
- Serum creatine < 1.5 x ULN
- Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)
- Serum creatine phosphokinase (CPK) ≤ 1.5 x ULN
- UA negative for hemoglobin and glucose and no greater than 1+ protein
- Any abnormalities must be assessed by the investigator as not clinically significant
- ECG without evidence of current or past MI, or ischemic heart disease
- Willing to provide signed informed consent
- Females: a negative serum or urine β-HCG pregnancy test at screening
- Female subjects of reproductive potential who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy and agree to consistently use contraception for at least 21 days prior to first vaccination until the last protocol visit.
- Male subjects participating in the study must agree to not attempt to impregnate a female, or participate in sperm donation programs
- Males engaging in sexual activity that could lead to pregnancy must use a condom from the date of receipt of the first study vaccine until the last protocol visit
- Agreement to use condoms for protection against HIV-1 transmission throughout the study
- Participants must be willing to comply with all study requirements and expected to be available for the duration of the study
- Participants must be willing to temporarily discontinue antiretroviral therapy for up to 12 wks. post-vaccinations
Exclusion Criteria:
- Known infection with HIV-1 subtype other than Clade B
- Chemotherapy for active malignancy in the past 12 mo.
- Prior vaccinations with any HIV-1 vaccine
- Prior vaccination against smallpox within the last 15 yrs.
- History of or known cardiac disease
- History of myositis
- Diagnosis of HIV-associated nephropathy
- Evidence of active HBV or HCV infection
- Framingham Global Risk Assessment Score consistent with high short-term (10 yr.) cardiac risk
- Receipt of immunomodulatory agents, systemic corticosteroids (including nonprescription street steroids), gamma globulin, or investigational agents (other than H1N1 influenza vaccine) within 6 mo. of screening
- Any immunization within 1 mo. of screening and within 2 wks. of any inoculation in this study
- Creatine supplements within 14 days of baseline and unwillingness to discontinue use throughout the trial
- Changes in ART regimen prior to entry due to virologic failure (not including toxicity)
- Pregnancy or breastfeeding
- Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participant safety
- Active alcohol or substance abuses
- Allergy to chicken egg derived products
- Contraindication to intramuscular injection
- Unwilling to forego vigorous exercise 3 days prior to each vaccination
Sites / Locations
- The University of Alabama at Birmingham Alabama Vaccine Research Clinic
- AIDS Research Alliance
- AIDS Research Consortium of Atlanta
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JS7 plasmid DNA and MVA62B vaccines
Arm Description
All subjects receive JS7 plasmid DNA (at 1 and 9 weeks) and MVA62B vaccines (17 and 25 weeks), followed (in 2 months after last vaccination) by a 12-week treatment interruption phase. Subjects reinstitute therapy after the treatment interruption and are followed for 6 months.
Outcomes
Primary Outcome Measures
Safety in all phases of study.
Frequency and severity of adverse events, laboratory abnormalities, and local and systemic reactogenicity signs and symptoms following vaccinations. Vaccination(virologic failure): HIV-1 RNA >200 copies/mL and CD4+ <350 cells/uL; genotypic resistance patterns of re-emergent virus. Treatment interruption:number(#)and percentage(%): 1)meet HIV-1 RNA and CD4+ criteria to re-institute anti-retroviral therapy before 12 wks; 2)genotypic resistance in re-emergent virus. Treatment reinstitution:# and %: 1)meet criteria for virologic failure; 2)genotypic resistance in patients with virologic failure.
Secondary Outcome Measures
Immunogenicity
Magnitude of interferon (ifn) gamma &/or interleukin-2 (IL-2) producing CD4+ and CD8+ T cells at 1 week (wk) post 2nd MVA (modified vaccinia ankara) vaccination (vacc); titer & avidity index of binding aby for Env at 2 wks post 2nd MVA vacc. Magnitude of ifn-gamma &/or IL-2 producing CD4+ & CD8+ cells, # and id of Gag-specific CD8+ responses & titers of binding aby for Env at 2 wks post detection of re-emergent virus. Log change in HIV-1 RNA from before antiretroviral therapy to end of treatment interruption; time to HIV-1 rebound to >200 copies/mL.
Full Information
NCT ID
NCT01378156
First Posted
July 30, 2010
Last Updated
November 9, 2017
Sponsor
GeoVax, Inc.
Collaborators
AIDS Research Consortium of Atlanta, University of Alabama at Birmingham, AIDS Research Alliance
1. Study Identification
Unique Protocol Identification Number
NCT01378156
Brief Title
A Safety and Immunogenicity Study of a Plasmid DNA Prime and MVA Boost Vaccine in HIV-1 Infected Adults on ART
Official Title
A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of pGA2/JS7 DNA and MVA/HIV62B in HIV-infected Adults With Suppressed Viremia Who Started ART Within 18 Months of a Negative HIV Antibody Test
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GeoVax, Inc.
Collaborators
AIDS Research Consortium of Atlanta, University of Alabama at Birmingham, AIDS Research Alliance
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
GV-TH-01 is an open label Phase 1 study of 9 HIV-1 infected adults with suppressed viremia who started anti-retroviral therapy (ART) within 18 months of a negative HIV antibody test. This study has 3 phases. The first phase is the vaccination phase, where patients are vaccinated with pGA2/JS7 (JS7)DNA and MVA62B vaccines on a prime/boost regimen. The second phase of the study is a treatment interruption phase, whereby ART is interrupted for a 12 week period approximately 8 weeks following the last vaccination. The third phase occurs after the 12 week treatment interruption phase and is called the treatment reinstitution phase, because subjects reinstitute ART and are followed for an additional 24 weeks. The primary objective is to evaluate the safety of the vaccines during the three phases of the study. A secondary objective is to evaluate the immunogenicity of the vaccines during the vaccination phase of the study.
Detailed Description
GV-TH-01 is an open label Phase 1 study of 9 HIV-1 infected adults with suppressed viremia who started anti-retroviral therapy (ART) within 18 months of a negative HIV antibody test. This study has 3 phases. The first phase is the vaccination phase, where patients are vaccinated with pGA2/JS7 (JS7)DNA and MVA62B vaccines on a prime/boost regimen at weeks 1 and 9 (JS7 DNA vaccine) and weeks 17 and 25 (MVA62B). Both vaccines express Gag, Pol, and Env. The second phase of the study is a treatment interruption phase, whereby ART is interrupted for a 12 week period approximately 8 weeks following the last vaccination. The third phase occurs after the 12 week treatment interruption phase and is called the treatment reinstitution phase, because subjects reinstitute ART and are followed for an additional 24 weeks. The primary objective is to evaluate the safety of the vaccines during the three phases of the study. A secondary objective is to evaluate the immunogenicity of the vaccines during the vaccination phase of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection
Keywords
Therapy for HIV Infection, Suppressive ART with no failures, Treatment interruption
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
JS7 plasmid DNA and MVA62B vaccines
Arm Type
Experimental
Arm Description
All subjects receive JS7 plasmid DNA (at 1 and 9 weeks) and MVA62B vaccines (17 and 25 weeks), followed (in 2 months after last vaccination) by a 12-week treatment interruption phase. Subjects reinstitute therapy after the treatment interruption and are followed for 6 months.
Intervention Type
Biological
Intervention Name(s)
JS7 plasmid DNA and MVA62B vaccine
Other Intervention Name(s)
pGA2/JS7 and MVA/HIV62B vaccine
Intervention Description
JS7 plasmid DNA (3 mg at weeks 1 and 9) and MVA62B vaccine (10(8) TCID(50) at weeks 17 and 25)
Primary Outcome Measure Information:
Title
Safety in all phases of study.
Description
Frequency and severity of adverse events, laboratory abnormalities, and local and systemic reactogenicity signs and symptoms following vaccinations. Vaccination(virologic failure): HIV-1 RNA >200 copies/mL and CD4+ <350 cells/uL; genotypic resistance patterns of re-emergent virus. Treatment interruption:number(#)and percentage(%): 1)meet HIV-1 RNA and CD4+ criteria to re-institute anti-retroviral therapy before 12 wks; 2)genotypic resistance in re-emergent virus. Treatment reinstitution:# and %: 1)meet criteria for virologic failure; 2)genotypic resistance in patients with virologic failure.
Time Frame
Throughout study - up to 77 weeks
Secondary Outcome Measure Information:
Title
Immunogenicity
Description
Magnitude of interferon (ifn) gamma &/or interleukin-2 (IL-2) producing CD4+ and CD8+ T cells at 1 week (wk) post 2nd MVA (modified vaccinia ankara) vaccination (vacc); titer & avidity index of binding aby for Env at 2 wks post 2nd MVA vacc. Magnitude of ifn-gamma &/or IL-2 producing CD4+ & CD8+ cells, # and id of Gag-specific CD8+ responses & titers of binding aby for Env at 2 wks post detection of re-emergent virus. Log change in HIV-1 RNA from before antiretroviral therapy to end of treatment interruption; time to HIV-1 rebound to >200 copies/mL.
Time Frame
Throughout vaccination and treatment interruption phases
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-50 yrs.
ART started within 18 mo. of last documented negative HIV Ab test, or within 13 mo. of last negative detuned HIV-1 Ab assay, or within 18 mo. of evolution of Western blot from indeterminate to positive in the presence of a positive Ab test
No changes to ART treatment within 4 wks. of study entry
Documentation of level of plasma HIV-1 RNA and CD4+ counts prior to ART
On stable suppressive ART [HIV-1 RNA < 50 copies/mL (PCR) or < 75 copies/mL (bDNA) for at least 6 mo. prior to starting vaccination]
No history of virologic failure
CD4+ > 500 cells/µL
Nadir CD4+ > 350 cells/µL unless measured in the setting of acute infection
Laboratory values:
Hemoglobin ≥ 10g/dL (male) or 9g/dL (women)
ANC > 1000 cells/µL
ALT, AST ≤ 2.5 ULN
Total bilirubin < 1.5 x ULN (≤ 5 x ULN on atazanavir)
Fasting glucose ≤ 125 mg/dL
Serum creatine < 1.5 x ULN
Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)
Serum creatine phosphokinase (CPK) ≤ 1.5 x ULN
UA negative for hemoglobin and glucose and no greater than 1+ protein
Any abnormalities must be assessed by the investigator as not clinically significant
ECG without evidence of current or past MI, or ischemic heart disease
Willing to provide signed informed consent
Females: a negative serum or urine β-HCG pregnancy test at screening
Female subjects of reproductive potential who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy and agree to consistently use contraception for at least 21 days prior to first vaccination until the last protocol visit.
Male subjects participating in the study must agree to not attempt to impregnate a female, or participate in sperm donation programs
Males engaging in sexual activity that could lead to pregnancy must use a condom from the date of receipt of the first study vaccine until the last protocol visit
Agreement to use condoms for protection against HIV-1 transmission throughout the study
Participants must be willing to comply with all study requirements and expected to be available for the duration of the study
Participants must be willing to temporarily discontinue antiretroviral therapy for up to 12 wks. post-vaccinations
Exclusion Criteria:
Known infection with HIV-1 subtype other than Clade B
Chemotherapy for active malignancy in the past 12 mo.
Prior vaccinations with any HIV-1 vaccine
Prior vaccination against smallpox within the last 15 yrs.
History of or known cardiac disease
History of myositis
Diagnosis of HIV-associated nephropathy
Evidence of active HBV or HCV infection
Framingham Global Risk Assessment Score consistent with high short-term (10 yr.) cardiac risk
Receipt of immunomodulatory agents, systemic corticosteroids (including nonprescription street steroids), gamma globulin, or investigational agents (other than H1N1 influenza vaccine) within 6 mo. of screening
Any immunization within 1 mo. of screening and within 2 wks. of any inoculation in this study
Creatine supplements within 14 days of baseline and unwillingness to discontinue use throughout the trial
Changes in ART regimen prior to entry due to virologic failure (not including toxicity)
Pregnancy or breastfeeding
Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participant safety
Active alcohol or substance abuses
Allergy to chicken egg derived products
Contraindication to intramuscular injection
Unwilling to forego vigorous exercise 3 days prior to each vaccination
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harriet L Robinson, PhD
Organizational Affiliation
GeoVax, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
The University of Alabama at Birmingham Alabama Vaccine Research Clinic
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
AIDS Research Alliance
City
Los Angeles
State/Province
California
ZIP/Postal Code
90015
Country
United States
Facility Name
AIDS Research Consortium of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30312
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27711228
Citation
Thompson M, Heath SL, Sweeton B, Williams K, Cunningham P, Keele BF, Sen S, Palmer BE, Chomont N, Xu Y, Basu R, Hellerstein MS, Kwa S, Robinson HL. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus. PLoS One. 2016 Oct 6;11(10):e0163164. doi: 10.1371/journal.pone.0163164. eCollection 2016.
Results Reference
result
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A Safety and Immunogenicity Study of a Plasmid DNA Prime and MVA Boost Vaccine in HIV-1 Infected Adults on ART
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