Safety and Immunogenicity of Recombinant HIV Vaccines for HIV/AIDS

Centers for Disease Control and Prevention, China

Status and phase: Unknown; Phase 1

Conditions: Acquired Immunodeficiency Syndrome

Treatments: Biological: Saline Solution; Biological: D-GPEi; Biological: M-GPE

Study type: Interventional

Funder types: Other

Identifiers

NCT01881581

CDCPChina001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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56 participants in 8 patient groups

Lower dose DNA or Placebo

Experimental group

Description:

2.0 mL lower dose D-GPEi (0.5mg) or Saline solution at weeks 0

Treatment:

Biological: D-GPEi

Biological: Saline Solution

Medium dose DNA or Placebo

Experimental group

Description:

2.0 mL medium dose D-GPEi (2mg) or Saline solution at weeks 0

Treatment:

Biological: D-GPEi

Biological: Saline Solution

High dose DNA or Placebo

Experimental group

Description:

2.0 mL high dose D-GPEi (4mg) or Saline solution at weeks 0

Treatment:

Biological: D-GPEi

Biological: Saline Solution

Lower dose MVA or Placebo

Experimental group

Description:

100μL lower dose M-GPE (3×10\^7pfu) or Saline solution at weeks 0

Treatment:

Biological: M-GPE

Biological: Saline Solution

Medium dose MVA or Placebo

Experimental group

Description:

100μL medium dose M-GPE (1×10\^8pfu) or Saline solution at weeks 0

Treatment:

Biological: M-GPE

Biological: Saline Solution

High dose MVA or Placebo

Experimental group

Description:

300μL high dose M-GPE (3×10\^8pfu) or Saline solution at weeks 0

Treatment:

Biological: M-GPE

Biological: Saline Solution

Low dose DNA+MVA or Placebo control

Experimental group

Description:

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

Treatment:

Biological: M-GPE

Biological: D-GPEi

Biological: Saline Solution

High dose DNA+MVA or Placebo control

Experimental group

Description:

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

Treatment:

Biological: M-GPE

Biological: D-GPEi

Biological: Saline Solution