Safety and Immunogenicity Study of a DNA Priming and MVA Boosting Strategy of HIV Vaccine

This study has been completed.
Sponsor:
Collaborators:
Swedish Institute for Communicable Disease Control, Sweden
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Instituto Nacional de Saúde, Mozambique
ClinicalTrials.gov Identifier:
NCT01407497
First received: August 1, 2011
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

While antiretroviral drugs have shown great promise in reducing HIV replication and thus in reducing HIV/AIDS associated morbi-mortality and HIV transmission, the cost is substantial and side effects are a potentially limiting factor. Development of an effective safe-affordable vaccine is likely to be the best way to stop further virus spread. The study aims to determine safety and immunogenicity of the DNA-vaccine at a dose of 600µg and 1200µg delivered id in combination with MVA-CMDR boost im.


Condition Intervention Phase
HIV Infections
Biological: DNA HIVIS and MVA-CMDR
Biological: Saline solution
Phase 1

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 Phase I Trial to Assess Safety and Immunogenicity of i.d. DNA Priming and i.m. MVA Boosting in Healthy Volunteers in Mozambique and to Develop Further HIV Vaccine Trial Capacity Building in Mozambique

Resource links provided by NLM:


Further study details as provided by Instituto Nacional de Saúde, Mozambique:

Primary Outcome Measures:
  • Adverse events (local and system reactogenicity) [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]
    The safety of immunization will be assessed by clinical features and standard clinical chemistry and hematological tests. Safety endpoints: Adverse events will be assessed using a standard format for soliciting local and systemic reactogenicity to the vaccine and collection of unsolicited adverse events. Solicited reactogenicity will be evaluated for 7 days following each vaccination. All other AE will be collected from the time of first injection until the end of the study follow-up period.

  • Immunogenicity [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]

    The primary immunogenicity endpoint will be determined by the interferon gamma (IFN-gama) enzyme linked immunospot (ELISPOT) assay.

    Secondary immunogenicity endpoints will include cellular immune responses determined by intracellular cytokine staining and T cell proliferation assays as well as binding antibody and neutralizing antibody responses.



Enrollment: 25
Study Start Date: August 2011
Study Completion Date: August 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IA
600 µg i.d. (separate plasmids pools) of DNA priming at weeks 0, 4 and 12 108 pfu i.m. MVA boosting at weeks 24 and 36
Biological: DNA HIVIS and MVA-CMDR
600 µg i.d. (separate plasmids pools) of DNA priming at weeks 0, 4 and 12; 108 pfu i.m. MVA boosting at weeks 24 and 36
Placebo Comparator: IB
2 x 0.1 ml of saline solution i.d at weeks 0, 4 and 12 saline solution i.m at weeks 24 and 36
Biological: Saline solution
2 x 0.1 ml of saline solution i.d at weeks 0, 4 and 12 ; saline solution i.m at weeks 24 and 36
Active Comparator: IIA
1200 µg i.d. (separate plasmids pools) of DNA priming at weeks 0, 4 and 12;108 pfu i.m. MVA boosting at weeks 24 and 36
Biological: DNA HIVIS and MVA-CMDR
1200 µg i.d. (separate plasmids pools) of DNA priming at weeks 0, 4 and 12 ; 108 pfu i.m. MVA boosting at weeks 24 and 36
Placebo Comparator: IIB
2 x 0.2 ml of saline solution i.d at weeks 0, 4 and 12 ; saline solution i.m at weeks 24 and 36
Biological: Saline solution
2 x 0.2 ml of saline solution i.d at weeks 0, 4 and 12 ; saline solution i.m at weeks 24 and 36

  Eligibility

Ages Eligible for Study:   18 Years to 26 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age: 18 to 26 years
  2. Willing to undergo HIV (Human Immunodeficiency Virus) counseling and testing
  3. Have a negative antigen/antibody or antibody ELISA for HIV infection
  4. Able to give informed consent
  5. Satisfactory completion of an assessment of understanding prior to enrolment defined as 89% correct answers after three opportunities to take the test
  6. Basic abilities to read and write
  7. Resident in Maputo, and willing to remain so for the duration of the study
  8. At low risk of HIV infection, defined as the absence of an identifiable risk factor/ behavior (their presence is therefore an exclusion criteria):

    • sexual partner with HIV
    • sexual partner with unknown HIV serostatus who is also unwilling to use protective condoms consistently in all sexual relations
    • sexual partner is known to be at high risk for HIV
    • more than one sexual partner in the last 6 months
    • history of being an alcoholic [as medically defined or more than 35 units /week]
    • history of Sexually Transmitted Infection (STI) within past 6 months
  9. Verbal assurances that adequate birth control methods are used not to conceive/father a child during the study and up to 3 months after the last vaccine injection.
  10. Women shall have a negative urine pregnancy test
  11. Be willing to practice safe sex for the duration of the study to avoid sexually transmitted infections including HIV
  12. Good health as determined by medical history, physical examination, clinical judgment and by key laboratory parameters as judged by the study physician.
  13. Laboratory criteria:

    • Hemoglobin >10.5g/dl
    • White blood cell count <13,000/mm3
    • Neutrophils >1,300/mm3
    • Lymphocytes >1.000/ mm3
    • Platelets >120,000/ mm3
    • Random Blood Glucose < 6.44 mmol/L; if elevated, then a Fasting Blood Glucose < 6.11mmol/L (according to DAIDS Table for Lab Criteria)
    • Bilirubin <1.25 x uln
    • Alanine transaminase (ALT) <1.25 x uln
    • Urine dipstick for protein and blood: negative or trace. (If either is ¿ 1+, complete urinalysis (UA) will be performed.

Exclusion Criteria:

  1. At risk of HIV infection as mentioned above in the inclusion criteria
  2. Active tuberculosis or other systemic infectious process elicited by review of systems, physical examination and laboratory detection
  3. A history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention
  4. Autoimmune disease by history and physical examination
  5. Hives or recurrent hives and severe eczema
  6. A history of psychiatric, medical (including traditional medicine) and/or substance abuse problems during the past 6 months that the investigator believes would adversely affect the volunteer's ability to participate in the trial
  7. History of epilepsy, or currently taking anti-epileptics
  8. Received blood or blood products or immunoglobulins in the past 3 months
  9. Receiving immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy
  10. Use of experimental therapeutic agents within 30 days of study entry
  11. Reception of any live, attenuated vaccine within 60 days of study entry.
  12. Abnormality in Electrocardiogram (ECG) that could indicate risk or make interpretation of vaccine effects difficult according to the study operating procedures
  13. Previously received an HIV vaccine candidate
  14. History of severe local or general reaction to vaccination defined as:

    • Local: Extensive, indurate redness and swelling involving most of the major circumference of the arm, not resolving within 72 hours
    • General: Fever >= 39.5 0C within 48 hours; anaphylaxis; bronchospasm; laryngeal edema; collapse; convulsions or encephalopathy within 72 hours
  15. Being a lactating mother
  16. Study site employees who are involved in the protocol and may have direct access to the immunogenicity results
  17. Unlikely to comply with protocol as judged by the principal investigator or his designate.
  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: NCT01407497

Locations
Mozambique
Centro de Investigação e Treino em Saúde de Polana Caniço
Maputo, Mozambique
Sponsors and Collaborators
Instituto Nacional de Saúde, Mozambique
Swedish Institute for Communicable Disease Control, Sweden
European and Developing Countries Clinical Trials Partnership (EDCTP)
Investigators
Principal Investigator: Ilesh Jani, PhD Instituto Nacional de Saúde
Principal Investigator: Nafissa Osman, MD, PhD Hospital Central de Maputo
  More Information

No publications provided

Responsible Party: Instituto Nacional de Saúde, Mozambique
ClinicalTrials.gov Identifier: NCT01407497     History of Changes
Other Study ID Numbers: TAMOVAC-01-MZ
Study First Received: August 1, 2011
Last Updated: December 3, 2013
Health Authority: Mozambique: Ministry of Health (MISAU)

Keywords provided by Instituto Nacional de Saúde, Mozambique:
HIV
Vaccine
DNA
Prevention

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
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014