Clinical Trial of Recombinant Adenovirus Type 5 AIDS Vaccine

Study Overview
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Brief Summary
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This is a randomized, double-blind placebo-controlled dose-escalation clinical trial to evaluate the safety and the immunogenicity of Adenoviral vector 5 HIV-1 vaccines in subjects receiving stable highly active antiretroviral therapy(HAART) .

Detailed Description
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Patients continue antiretroviral medications throughout the course of this study. Three groups of patients receive dose-escalation (2×10^9VP, 2×10^10VP or 2×10^11VP) injections of Adenovirus vector vaccine (Ad5-gag). Two weeks post immunization of lower dose, if the vaccine is safe and well tolerant, the next dose of immunization will begin. patients are monitored for safety 72 hours after each immunization. In addition, each patient records adverse events in a diary. Patients have regular physical exams, pregnancy tests, and blood drawn for virologic and immunologic assessments. The induction of HIV-specific responses will be measured.

Official Title
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Phase I Clinical Trial of Recombinant Adenovirus Type 5 Therapeutic AIDS Vaccine Expressing Gag

Conditions
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Acquired Immunodeficiency Syndrome

Intervention / Treatment
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* Biological: Ad5-gag
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are willing to participate this study and available for follow-up for the duration of the study. Men and women aged 18-50 years. Are HIV-positive. Have been taking stable anti-HIV drugs for at least 6 months. CD4 count ≥ 350 cells/mm3 Plasma viral load < 50 copies/ml. Willing to use acceptable forms of contraception at least 21 days prior to first vaccination until 56 days after the last vaccination. Exclusion Criteria: Pregnancy or breast-feeding. History of previous vaccination with an HIV-1 vaccine. Use of immunoinhibitory agents, such as corticosteroids or cytotoxic drugs by oral administration, injection route or inhalation route within 6 months of study entry (But corticosteroids used for allergic rhinitis and skin topical application of corticosteroids were not included); Use of immunomodulatory agents including but not limited to interleukin-2(IL-2） and granulocyte-macrophage colony-stimulating factor (GM-CSF) within 30 days of study entry. Use of blood products within 3 months of study entry. Use of other experimental drugs within 3 months of study entry. Any immunization within 3 months of study entry. Comply with any of the following items： Active pulmonary tuberculosis； History of serious adverse reaction to other vaccines； Serious asthma； Have untreated thyroid disease; Syphilis Laboratory values（Comply with any of the following items）: Hemoglobin < 100 g/L (male subjects)，<90 g/L (female subjects)； Absolute neutrophil count ≤ 1000 cells/mm3； Serum creatinine ≥15 mg/L，endogenous creatinine clearance rate <50 ml/min； alanine aminotransferase（ALT）, aspartate aminotransferase(AST) ≥3× upper limit of normal range； Total bilirubin ≥2× upper limit of normal range Clinically significant electrocardiogram changes. Hypertension ( If it is well controlled by medication and is less than 150/100mmHg , should not be excluded) and other cardiac disease； Any medical, psychiatric, social condition, occupational reason judged by the investigator that would limit the evaluation of a subject.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose Ad5-gag or Placebo<br>1ml low dose Ad5-gag(2x10^9VP) or Preservation solution at weeks 0 and weeks 4. | Biological: Ad5-gag<br>* Ad5-gag is used as vaccine in all arms.<br>Biological: Placebo<br>* Preservation Solution is used as control in all arms.<br>* Other names: Preservation Solution;|
| Experimental: Medium dose Ad5-gag or Placebo<br>1ml medium dose Ad5-gag(2x10^10VP) or Preservation solution at weeks 0 and weeks 4. | Biological: Ad5-gag<br>* Ad5-gag is used as vaccine in all arms.<br>Biological: Placebo<br>* Preservation Solution is used as control in all arms.<br>* Other names: Preservation Solution;|
| Experimental: High dose Ad5-gag or Placebo<br>1ml high dose Ad5-gag(2x10^11VP) or Preservation solution at weeks 0 and weeks 4. | Biological: Ad5-gag<br>* Ad5-gag is used as vaccine in all arms.<br>Biological: Placebo<br>* Preservation Solution is used as control in all arms.<br>* Other names: Preservation Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence, intensity and relationship to vaccination of local and systemic adverse events | To evaluate the safety and tolerance of a replication defective adenovirus expressing HIV-1 gag in HIV-1 infected subjects on highly active antiretroviral therapy. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of vaccine | To evaluate immune responses pre- and post-immunization and between the vaccine and placebo groups. | 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic Vaccine HIV Adenovirus type 5 vector