Clinical trial NCT01881581: Safety and Immunogenicity of Recombinant HIV Vaccines for HIV/AIDS
Official title: A Phase I Double-Blind Study to Evaluate the Safety and Immunogenicity of HIV Prime/Boost Vaccine Using DNA and MVA for HIV-1/AIDS
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acquired Immunodeficiency Syndrome
Keywords: Therapeutic
Vaccine
HIV
MVA
DNA
Lead sponsor: Centers for Disease Control and Prevention, China
Sponsor class: OTHER_GOV
Collaborators: name: Beijing Ditan Hospital
name: National Institutes for Food and Drug Control, China
First posted: 2013-06-19
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence, intensity and relationship to vaccination of local and systemic adverse events
timeFrame: 8 months
Secondary outcomes:
measure: Immunogenicity of vaccine
timeFrame: 14 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital of Capital Medical University
Study officials:
affiliation: Beijng Ditan Hospital of Capital Medical University
name: Xingwang Li, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijng Ditan Hospital of Capital Medical University
name: Rongmeng Jiang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute for Viral Disease Control and Prevention, China CDC
name: Yi Zeng
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute for Viral Disease Control and Prevention, China CDC
name: Xia Feng, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute for Viral Disease Control and Prevention, China CDC
name: Ke Xu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: