Single-Blind, Controlled Safety and Immunogenicity Study of Recombinant MVA Virus to Treat HIV Infection

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Bavarian Nordic
ClinicalTrials.gov Identifier:
NCT00390078
First received: October 18, 2006
Last updated: July 9, 2009
Last verified: July 2009
  Purpose

At the end of 2004 there were more than 40 million people infected Worldwide with HIV, with an estimated 16,000 new infections every day (UNAIDS, 2004). The HIV epidemic threatens whole societies particularly in Africa and Asia and rates of infections in the Western Countries have also increased over the last few years. However, despite more than 15 years of research, an effective vaccine against HIV and acquired immunodeficiency syndrome (AIDS) has still not been developed.

There is considerable evidence that cellular immune responses can effectively control HIV-1 replication during acute and chronic infections thereby possibly protecting individuals from infection and preventing the spread of HIV. To be truly effective in the general population, a vaccine must induce responses specific to immunologically conserved regions. The epitope-based vaccine MVA-mBN32 represent a very logical approach to this problem because its potential to elicit a polyfunctional immune response and to focus these responses to conserved epitopes.

In this study the safety, tolerability and immunogenicity of a recombinant MVA-BN® expressing CTL and HTL epitopes of HIV-1 (MVA-mBN32) vs. the vector control MVA-BN® in 30 HIV-infected subjects will be examined. This will include a full analysis of CD4+ T helper cells and CD8+ CTL responses to these epitopes, to establish the potential of such a homologous prime-boost vaccine approach to induce a broad cell-mediated response to different HIV antigens.


Condition Intervention Phase
HIV Infections
Biological: MVA-mBN32
Biological: IMVAMUNE
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Single-Blind, Randomized, Controlled, Phase I/II Vaccination Study on Safety and Immunogenicity of a Recombinant MVA-HIV Polytope Vaccine (MVA-mBN32) in HIV-1 Infected Patients With CD4 Counts > 250/µl

Resource links provided by NLM:


Further study details as provided by Bavarian Nordic:

Primary Outcome Measures:
  • To compare the safety and reactogenicity of the recombinant MVA-mBN32 expressing functional HIV epitopes and MVA-BN® following repeated vaccination in HIV-1 infected patients [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2007
Study Completion Date: January 2009
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
20 Subjects, 1x 10E8_TCID50 MVA-mBN32
Biological: MVA-mBN32
3 immunizations: 1x 10E8_TCID50 MVA-mBN32
Placebo Comparator: 2
10 Subjects 1x 10E8_TCID50 IMVAMUNE
Biological: IMVAMUNE
3 immunizations: 1x 10E8_TCID50 IMVAMUNE

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects, aged 18 to 50 years.
  2. HIV-1 infection.
  3. Stable on HAART with regard to immunologic and clinical parameters for at least 6 consecutive months prior to study entry.
  4. Plasma HIV RNA level < 50 copies/ml for at least 6 months
  5. Plasma HIV-1 RNA levels of < 50 copies/ml at study entry.
  6. CD4 cells above 250/µl.
  7. CD4 nadir > 200/µl.
  8. HLA-A2, HLA-A3 or HLA-B7 positive.
  9. Laboratory criteria (all of the following must be fulfilled):

    Adequate bone marrow reserve, Adequate renal function, Adequate hepatic function, Cardiac enzymes within normal range

  10. For women, negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to each vaccination.
  11. If the volunteer is female and of childbearing potential, she has used adequate contraceptive precautions for 30 days prior to the first vaccination and agrees to use an acceptable method of contraception, and not become pregnant for at least 56 days after the last vaccination.
  12. Read, signed and dated informed consent document.

EXCLUSION CRITERIA:

  1. Pregnancy or breast-feeding.
  2. Uncontrolled serious infection
  3. History of any serious medical condition, which in the opinion of the investigator, would compromise the safety of the subject.
  4. History of or active autoimmune disease.
  5. History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure.
  6. History of chronic alcohol abuse (40g / day for at least 6 months) and/or intravenous drug abuse (within the past 6 month).
  7. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
  8. History of anaphylaxis or severe allergic reaction.
  9. Acute disease (a moderate or severe illness with or without a fever) at the time of enrolment.
  10. Any continuous therapy that may influence CD4 counts other than anti-retroviral therapy
  11. Any vaccinations with live vaccines within a period starting 30 days prior to administration of the vaccine and ending 30 days after administration of the study vaccine. Any vaccinations with killed vaccines within a period starting 14 days prior to administration of the study vaccine and ending 14 days after administration of the study vaccine.
  12. Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs during a period starting from six months prior to administration of the vaccine and ending at study conclusion.
  13. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to administration of the vaccine and ending at study conclusion.
  14. Prior use of any HIV vaccine or vaccinia immunization within the last 5 years.
  15. Use of any investigational or non-registered drug or vaccine.
  16. History or clinical manifestation of clinically significant mental illness or severe haematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
  17. ECG with clinical significance.
  18. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor.
  19. Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool. (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE: This criterion applies only to volunteers 20 years of age and older.
  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: NCT00390078

Locations
Germany
Charité, Campus Virchow-Klinikum
Berlin, Germany, 13353
Sponsors and Collaborators
Bavarian Nordic
Investigators
Study Director: Johannes Hain, PhD Bavarian Nordic
  More Information

No publications provided

Responsible Party: Monika Fluer, Bavarian Nordic
ClinicalTrials.gov Identifier: NCT00390078     History of Changes
Other Study ID Numbers: HIV-POL-002, NIAID Cont. No. N01-AI-40072
Study First Received: October 18, 2006
Last Updated: July 9, 2009
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Bavarian Nordic:
Vaccine
Safety
T-cell epitope
Acquired Immune Deficiency Syndrome Virus
HIV Therapeutic Vaccine

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

ClinicalTrials.gov processed this record on August 28, 2014