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| Name | Class |
|---|---|
| Beijing Ditan Hospital | OTHER |
| National Institutes for Food and Drug Control, China | OTHER |
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This is a randomized, double-blind placebo-controlled dose-escalation clinical trial to evaluate the safety and the immunogenicity of DNA and modified vaccinia virus Ankara (MVA) HIV-1 vaccines in subjects receiving stable highly active antiretroviral therapy (HAART) who have an HIV-1 RNA < 50 copies/mm3 and CD4+ T cells count ≥ 350 cells/mm3.
HIV-infected patients treated with antiretroviral therapy for prolonged periods of time may show decreased levels of HIV-specific immune responses. In these patients, a prime-boost vaccine strategy may induce both humoral and cell-mediated immunity. The hypothesis of this study is that the vaccine strategy selected will be both safe and immunogenic in the patient population being tested.
Patients continue antiretroviral medications throughout the course of this study. Three groups of patients receive dose-escalation (0.5mg, 2mg or 4mg) intramuscular injections of DNA vaccine (D-GPEi) respectively, the other three groups of patients receive dose-escalation (3×10^7pfu, 1×10^8pfu or 3×10^8pfu) intradermal injections of MVA vaccine (M-GPE), two weeks post immunization of lower dose, if the vaccine is safe and well tolerant, the next dose of immunization will begin. After the maximum tolerated dose of DNA and MVA is identified, DNA prime/ MVA boosting will be tested in another two groups of patients. Lower or the maximum tolerated dose of D-GPEi was used at week 0 and 1, lower or the maximum tolerated dose of M-GPE was used at week 2 and 3, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lower dose DNA or Placebo | Experimental | 2.0 mL lower dose D-GPEi (0.5mg) or Saline solution at weeks 0 |
|
| Medium dose DNA or Placebo | Experimental | 2.0 mL medium dose D-GPEi (2mg) or Saline solution at weeks 0 |
|
| High dose DNA or Placebo | Experimental | 2.0 mL high dose D-GPEi (4mg) or Saline solution at weeks 0 |
|
| Lower dose MVA or Placebo | Experimental | 100μL lower dose M-GPE (3×10^7pfu) or Saline solution at weeks 0 |
|
| Medium dose MVA or Placebo | Experimental | 100μL medium dose M-GPE (1×10^8pfu) or Saline solution at weeks 0 |
|
| High dose MVA or Placebo |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saline Solution | Biological | Saline Solution is used as control in all arms. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence, intensity and relationship to vaccination of local and systemic adverse events | To evaluate the safety and tolerance of a DNA and a replication-defective MVA vaccine expressing HIV-1 gag-pol and env in HIV-1 infected subjects on highly active antiretroviral therapy. Frequency and severity of adverse events, laboratory abnormalities, and local and systemic reactogenicity signs and symptoms following vaccinations | 8 months |
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity of vaccine | Changes in CD4+ and CD8+ T-cell counts pre- and post-immunization and between the vaccine and placebo groups Changes in viral load pre- and post-immunization and between the vaccine and placebo groups Magnitude and breadth of HIV-1 specific CD8+ T cell responses as determined by interferon-γ(IFN-γ) enzyme-linked immunospot (ELISPOT) using overlapping HIV peptides for gag, pol and env Changes in HIV-1 Gp160-specific antibody responses pre- and post-immunization and between the vaccine and placebo groups |
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Inclusion Criteria:
Exclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Xingwang Li, M.D. | Beijng Ditan Hospital of Capital Medical University | Principal Investigator |
| Rongmeng Jiang, M.D. | Beijng Ditan Hospital of Capital Medical University | Principal Investigator |
| Yi Zeng | National Institute for Viral Disease Control and Prevention, China CDC | Principal Investigator |
| Xia Feng, Ph.D | National Institute for Viral Disease Control and Prevention, China CDC | Principal Investigator |
| Ke Xu, Ph.D | National Institute for Viral Disease Control and Prevention, China CDC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Ditan Hospital of Capital Medical University | Recruiting | Beijing | China |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Experimental |
300μL high dose M-GPE (3×10^8pfu) or Saline solution at weeks 0 |
|
| Low dose DNA+MVA or Placebo control | Experimental | The dose below the maximum tolerated dose of D-GPEi or 2.0 mL Saline solution at week 0,1; The dose below the maximum tolerated dose of M-GPE or 100/300μL Saline solution at week 2,3 |
|
| High dose DNA+MVA or Placebo control | Experimental | The maximum tolerated dose of D-GPEi or 2.0 mL Saline solution at week 0,1;The maximum tolerated dose of M-GPE or 100/300μL Saline solution at week 2,3 |
|
| D-GPEi | Biological | D-GPEi is used in Arm A,B,C,G and H. |
|
| M-GPE | Biological | M-GPE is used in Arm D,E,F,G and H |
|
| 14 months |
| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |