A Phase IIA Trial to Evaluate the Safety and Immunogenicity of a DNA HIV-1 Vaccine Followed by an MVA HIV-1 Vaccine in HIV-uninfected Volunteers

This study has been completed.
Sponsor:
Collaborators:
Medical Research Council-Oxford
University of Nairobi
Information provided by:
International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier:
NCT01371175
First received: May 31, 2011
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

The purpose of this study is to evaluate the safety and tolerability of plasmid DNA and recombinant MVA (Modified Vaccinia Virus Ankara) in a prime-boost regimen.

Approximately 111 volunteers (90 vaccine recipients/21 placebo recipients) will be enrolled at two sites. Approximately 56 volunteers will be enrolled at each site. An over-enrolment of up to 10% (approximately 10 additional volunteers) will be permitted in the study.


Condition Intervention Phase
HIV Infections
Biological: DNA.HIVA
Biological: MVA.HIVA
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Placebo-Controlled, Dosage-Escalating Phase 2A Study, Double-Blinded With Respect to Assignment to Either Vaccine or Placebo, to Evaluate the Safety and Immunogenicity of a DNA HIV-1 Vaccine Administered Intramuscularly Followed by an MVA HIV-1 Vaccine Administered at Three Different Dosage Levels and by Three Different Routes to HIV-Uninfected, Healthy, Volunteers.

Resource links provided by NLM:


Further study details as provided by International AIDS Vaccine Initiative:

Primary Outcome Measures:
  • Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity: Proportion of volunteers with HIV-1 specific T-cell responses by ELISPOT assay. [ Time Frame: Day 0, Month 1, Month 2, Month 5, Month 6, Month 8, Month 9, Month 12, Month 18 ] [ Designated as safety issue: No ]

Enrollment: 115
Study Start Date: April 2003
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered subcutaneously. Vaccine:Placebo =12/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
5x10^6 pfu MVA or placebo
Experimental: Group B
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intramuscularly. Vaccine:Placebo =12/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
5x10^6 pfu MVA or placebo
Experimental: Group C
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intradermally. Vaccine:Placebo =18/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
5x10^7 pfu MVA or placebo
Experimental: Group D
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered subcutaneously. Vaccine:Placebo =12/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
5x10^7 pfu MVA or placebo
Experimental: Group E
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intramuscularly. Vaccine:Placebo =12/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
5x10^7 pfu MVA or placebo
Biological: MVA.HIVA
2.5x10^8 pfu MVA or placebo
Experimental: Group F
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered subcutaneously. Vaccine:Placebo =12/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
2.5x10^8 pfu MVA or placebo
Experimental: Group G
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intramuscularly. Vaccine:Placebo =12/3
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Experimental: Groups C2/D2/E2 (Subgroups of C,D,E)
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and Month 12+ (volunteers offered second MVA/placebo more than 12 months (late boost) after their enrollment into their original treatment assignment) delivered ID, SC, or IM according to original randomization. Vaccine:Placebo = blinded ratio, maximum in C2/D2/E2 = 16.
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
5x10^7 pfu MVA or placebo
Experimental: Group F2/G2 (Subgroup of F and G)
DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and Month 12+ (volunteers offered second MVA/placebo more than 12 months (late boost) after their enrollment into their original treatment assignment) delivered either SC or IM according to original randomization. Vaccine:Placebo = blinded ratio, maximum in F/G= 29.
Biological: DNA.HIVA
0.5mg DNA.HIVA or placebo
Biological: MVA.HIVA
2.5x10^8 pfu MVA or placebo

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  1. Healthy males and females;
  2. Age at least 18 years on the day of screening and no greater than 60 years on the day of enrolment;
  3. Available for follow up for the planned duration of the study (screening plus 18 months);
  4. Able to give written informed consent;
  5. Does not engage in risk behaviour as defined by the protocol, willing to undergo HIV testing and receive results;
  6. If sexually active female, using an effective method of contraception (combined oral contraceptive pill; injectable contraceptive; IUCD; condoms; anatomical sterility in self or partner) from screening until at least 4 months after last vaccination and willing to undergo urine pregnancy tests at screening and prior to each vaccination and 4 months after the last vaccination;
  7. If sexually active male, willing to use an effective method of contraception (such as condoms) from screening until 4 months after the last vaccination.

Exclusion Criteria:

  1. Clinically relevant abnormality on history or examination including history of immunodeficiency or use of systemic corticosteroids, immunosuppressive, antiviral, anticancer, or other medications considered significant by the designated trial physician in last 6 months;
  2. Presence of any chronic condition;
  3. Any of the following abnormal laboratory parameters that are moderate, severe, or very severe: haematology (haemoglobin, absolute neutrophil count absolute lymphocyte count , absolute CD4 count, platelets); urinalysis, biochemistries (total bilirubin, creatinine, AST, ALT). Volunteers with mild laboratory abnormalities which are judged by the principal investigator or designee to be not clinically significant may be enrolled.
  4. If female, pregnant or planning a pregnancy within 4 months after last vaccination or lactating;
  5. Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment;
  6. Receipt of blood transfusion or blood products 6 months prior to enrolment;
  7. Participation in another clinical trial of an investigational product currently or within last 12 weeks or expected participation during this study;
  8. History of severe local or general reaction to vaccination or history of allergic reactions;
  9. History of grand-mal epilepsy, or currently taking anti-epileptics;
  10. Confirmed HIV-1 or HIV-2 seropositive;
  11. Positive for hepatitis B (surface antigen) or confirmed diagnosis of active syphilis at the time of enrolment (RPR positive and TPHA positive or equivalent), positive for hepatitis C antibodies;
  12. Unlikely to comply with protocol. Prior receipt of smallpox vaccination should be documented, but will not be an exclusion criterion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371175

Locations
Kenya
KAVI (Kenya AIDS Vaccine Initiative)
Nairobi, Kenya
United Kingdom
Guys and St. Thomas' Hospital
London, United Kingdom
Sponsors and Collaborators
International AIDS Vaccine Initiative
Medical Research Council-Oxford
University of Nairobi
Investigators
Principal Investigator: Barry S. Peters, MD Guys and St. Thomas' Hospital
Principal Investigator: Walter Jaoko KAVI (Kenya AIDS Vaccine Initiative)
  More Information

Additional Information:
No publications provided

Responsible Party: Patricia Fast, MD, PhD. Chief Medical Officer, International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier: NCT01371175     History of Changes
Other Study ID Numbers: IAVI 010
Study First Received: May 31, 2011
Last Updated: June 9, 2011
Health Authority: Kenya: Kenyatta National Hospital Ethics and Research Committee
Kenya: National Council for Science and Technology
United Kingdom: Riverside Research Ethics Committee
United Kingdom: St Thomas' Hospital Research Ethics Committee
United Kingdom: Department of Health
United Kingdom: National Health Service

Keywords provided by International AIDS Vaccine Initiative:
HIV

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 30, 2014