Safety Study of an Additional MVA Vaccine in Volunteers Who Received 3 DNA Vaccines Followed by 2 MVA Vaccines

NCT ID: NCT01461447

Last Updated: 2012-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2012-05-31

Brief Summary

The purpose of the study is to determine the safety and immunogenecity of a third MVA in the HIVIS 03 volunteers who have received 3 HIVIS DNA vaccines followed by boosting with 2 MVA vaccines.

The investigators postulate that the Immune responses that were observed in the HIVIS 03 trial are likely to wane over time. To date it is unknown how these responses should best be maintained. In this study the investigators seek to boost immune responses, especially the antibody responses induced by the second MVA boost.

Since the HIV specific antibodies were induced only after the second MVA injection, it is hypothesized that a 3rd MVA will give rise to even higher and sustained antibody titers.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

MVA

Volunteers who were primed with 3 HIVIS DNA and further boosted with 2 MVA vaccine will receive a third MVA there shall not be an comparator for this study.

Group Type: EXPERIMENTAL

Modified Vaccinia Ankara

Intervention Type: BIOLOGICAL

Healthy volunteers will receive intramuscularly 1 injection of MVA-CMDR 1ml (Total 10 power 8 pfu) boost injection in the left deltoid muscle.

Interventions

Modified Vaccinia Ankara

Healthy volunteers will receive intramuscularly 1 injection of MVA-CMDR 1ml (Total 10 power 8 pfu) boost injection in the left deltoid muscle.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Have completed the HIVIS03/TaMoVac01 WP1 protocol and received the active vaccine

2. Willing to undergo counseling and HIV testing

3. Are not infected by HIV infection as indicated by a negative PCR reaction against HIV.

4. Able to give informed consent

5. Resident in Dar es Salaam, and willing to remain so for the duration of the study

6. At low risk of HIV infection, defined as the absence of an identifiable risk factor/ behavior:

• 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 STI within past 6 months.

7. Verbal assurances that adequate birth control measures are used not to conceive/father a child during the study and up to 4 months after the 3rd MVA vaccine injection

8. Have a negative urinary pregnancy test for females

9. ECG findings that neither pose a risk for the vaccination nor preclude evaluation of peri/myocarditis.

10. Be willing to practice safe sex for the duration of the study to avoid sexually transmitted infections including HIV.

11. Good health as determined by medical history, physical examination, clinical judgment and by key laboratory parameters

Reference ranges will be in accordance with data generated at MUHAS for hematology values, and biochemical parameters. Exclusion by presence of Diabetes mellitus will be based on the WHO cut-off value of a Fasting Blood Glucose >7.8 mmol/l

No grade 1 or higher routine laboratory parameters (see section on appendix 3 DAIDS chart for Definitions). Hence lab parameters have to be as follows:

• Hb >10.5g/dl
• White blood cell count >1,300/mm3
• Lymphocytes >1.0/ mm3
• Platelets >120,000/ mm3
• CD4 >400cells/ mm3
• Random Blood Glucose 2.5-7.0 mmol/L; if elevated, then a Fasting Blood Glucose <7.8 mmol/l
• Bilirubin <1.25 x uln
• ALT <1.25 x uln
• Creatinine <1.25 x uln
• Urine dipstick for protein and blood: negative or trace. (If either is ≥ 1+, obtain complete urinalysis (UA). If microscopic UA confirms evidence of hematuria or if proteinuria ≥ 1+, the volunteer is ineligible).

Exclusion Criteria

1. Active tuberculosis or other systemic infectious process elicited by review of systems, physical examination and laboratory detection. Such as detection of Hepatitis B surface antigen, or active syphilis.

2. Have a history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention

3. Autoimmune disease by history and physical examination.

4. Severe eczema

5. Have history of psychiatric, medical 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.

6. History of grand-mal epilepsy, or currently taking anti-epileptics

7. Have received blood or blood products or immunoglobulins in the past 3 months.

8. Are receiving immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy.

9. Have used experimental therapeutic agents within 30 days of study entry.

10. Have received any live, attenuated vaccine within 60 days of study entry. {NOTE: Medically indicated subunit or killed vaccines (e.g., Hepatitis A or Hepatitis B) are not exclusionary but should be given at least 2 weeks before or after HIV immunization to avoid potential confusion of adverse reactions}.

11. History of severe local or general reaction to vaccination defined as:

• Local: Extensive, indurated 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 oedema; collapse; convulsions or encephalopathy within 72 hours

12. Are lactating mothers

13. Are study site employees who are involved in the protocol and may have direct access to the immunogenicity results

14. Unlikely to comply with protocol as judged by the principal investigator or her designate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Swedish Institute for Infectious Disease Control

OTHER

Sponsor Role: collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

Muhimbili University of Health and Allied Sciences

OTHER

Sponsor Role: lead

Responsible Party

Patricia Jane Munseri

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Muhimbili University of Health and Allied Sciences

Dar es Salaam, , Tanzania

Countries

Tanzania

Other Identifiers

HIVIS 06

Identifier Type: -

Identifier Source: org_study_id