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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: DNA HIVIS and MVA-CMDR
* Biological: DNA HIVIS and MVA-CMDR
* Biological: Saline solution
* Biological: Saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 to 26 years Willing to undergo HIV (Human Immunodeficiency Virus) counseling and testing Have a negative antigen/antibody or antibody ELISA for HIV infection Able to give informed consent Satisfactory completion of an assessment of understanding prior to enrolment defined as 89% correct answers after three opportunities to take the test Basic abilities to read and write Resident in Maputo, and willing to remain so for the duration of the study 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 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. Women shall have a negative urine pregnancy test Be willing to practice safe sex for the duration of the study to avoid sexually transmitted infections including HIV Good health as determined by medical history, physical examination, clinical judgment and by key laboratory parameters as judged by the study physician. 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: At risk of HIV infection as mentioned above in the inclusion criteria Active tuberculosis or other systemic infectious process elicited by review of systems, physical examination and laboratory detection A history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention Autoimmune disease by history and physical examination Hives or recurrent hives and severe eczema 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 History of epilepsy, or currently taking anti-epileptics Received blood or blood products or immunoglobulins in the past 3 months Receiving immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy Use of experimental therapeutic agents within 30 days of study entry Reception of any live, attenuated vaccine within 60 days of study entry. Abnormality in Electrocardiogram (ECG) that could indicate risk or make interpretation of vaccine effects difficult according to the study operating procedures Previously received an HIV vaccine candidate 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 Being a lactating mother Study site employees who are involved in the protocol and may have direct access to the immunogenicity results Unlikely to comply with protocol as judged by the principal investigator or his designate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 26 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IA<br>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<br>* 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<br>|
| Placebo Comparator: IB<br>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<br>* 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<br>|
| Active Comparator: IIA<br>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<br>* 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<br>|
| Placebo Comparator: IIB<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (local and system reactogenicity) | 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. | 44 weeks | 
| Immunogenicity | 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. | 44 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Vaccine, DNA, Prevention