A Safety and Immunogenicity Study of a Plasmid DNA Prime and MVA Boost Vaccine in HIV-1 Infected Adults on ART

NCT01378156 | Completed Phase 1

• 1 other identifier: GV-TH-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

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.

Conditions

HIV-1 Infection

Keywords

Therapy for HIV Infection; Suppressive ART with no failures; Treatment interruption

Outcome Measures

Primary Outcomes (1)

• 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.

  Throughout study - up to 77 weeks

Secondary Outcomes (1)

• Immunogenicity

  Throughout vaccination and treatment interruption phases

Study Arms (1)

JS7 plasmid DNA and MVA62B vaccines

EXPERIMENTAL

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.

Biological: JS7 plasmid DNA and MVA62B vaccine

Interventions

JS7 plasmid DNA and MVA62B vaccine BIOLOGICAL

JS7 plasmid DNA (3 mg at weeks 1 and 9) and MVA62B vaccine (10(8) TCID(50) at weeks 17 and 25)

Also known as: pGA2/JS7 and MVA/HIV62B vaccine

JS7 plasmid DNA and MVA62B vaccines

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GeoVax, Inc.: lead
• AIDS Research Consortium of Atlanta: collaborator
• University of Alabama at Birmingham: collaborator
• AIDS Research Alliance: collaborator

Study Sites (3)

The University of Alabama at Birmingham Alabama Vaccine Research Clinic

Birmingham, Alabama, 35294, United States

Location

AIDS Research Alliance

Los Angeles, California, 90015, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30312, United States

Location

Related Publications (1)

• 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.

  PMID: 27711228 RESULT

Study Officials

• Harriet L Robinson, PhD

  GeoVax, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2010
• First Posted: June 22, 2011
• Study Start: June 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 14, 2017

Record last verified: 2017-11

Locations

US (3)