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Safety and Immunogenicity of Recombinant HIV Vaccines for HIV/AIDS

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Centers for Disease Control and Prevention, China
Sponsor:
Collaborators:
Beijing Ditan hospital of Capital Medical University
National Institutes for Food and Drug Control
Information provided by (Responsible Party):
Yi Zeng, Centers for Disease Control and Prevention, China
ClinicalTrials.gov Identifier:
NCT01881581
First received: June 16, 2013
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Acquired Immunodeficiency Syndrome
Biological: Saline Solution
Biological: D-GPEi
Biological: M-GPE
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention, China:

Primary Outcome Measures:
  • Occurrence, intensity and relationship to vaccination of local and systemic adverse events [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]

    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



Secondary Outcome Measures:
  • Immunogenicity of vaccine [ Time Frame: 14 months ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 56
Study Start Date: June 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lower dose DNA or Placebo
2.0 mL lower dose D-GPEi (0.5mg) or Saline solution at weeks 0
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: D-GPEi
D-GPEi is used in Arm A,B,C,G and H.
Experimental: Medium dose DNA or Placebo
2.0 mL medium dose D-GPEi (2mg) or Saline solution at weeks 0
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: D-GPEi
D-GPEi is used in Arm A,B,C,G and H.
Experimental: High dose DNA or Placebo
2.0 mL high dose D-GPEi (4mg) or Saline solution at weeks 0
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: D-GPEi
D-GPEi is used in Arm A,B,C,G and H.
Experimental: Lower dose MVA or Placebo
100μL lower dose M-GPE (3×10^7pfu) or Saline solution at weeks 0
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: M-GPE
M-GPE is used in Arm D,E,F,G and H
Experimental: Medium dose MVA or Placebo
100μL medium dose M-GPE (1×10^8pfu) or Saline solution at weeks 0
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: M-GPE
M-GPE is used in Arm D,E,F,G and H
Experimental: High dose MVA or Placebo
300μL high dose M-GPE (3×10^8pfu) or Saline solution at weeks 0
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: M-GPE
M-GPE is used in Arm D,E,F,G and H
Experimental: Low dose DNA+MVA or Placebo control
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
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: D-GPEi
D-GPEi is used in Arm A,B,C,G and H.
Biological: M-GPE
M-GPE is used in Arm D,E,F,G and H
Experimental: High dose DNA+MVA or Placebo control
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
Biological: Saline Solution
Saline Solution is used as control in all arms.
Biological: D-GPEi
D-GPEi is used in Arm A,B,C,G and H.
Biological: M-GPE
M-GPE is used in Arm D,E,F,G and H

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01881581

Locations
China
Beijing Ditan Hospital of Capital Medical University Recruiting
Beijing, China
Contact: Xingwang Li    15611973658    ditanlxw@yahoo.com.cn   
Principal Investigator: Xingwang Li         
Sub-Investigator: Rongmeng Jiang         
Sponsors and Collaborators
Centers for Disease Control and Prevention, China
Beijing Ditan hospital of Capital Medical University
National Institutes for Food and Drug Control
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Yi Zeng, Departement Director, Centers for Disease Control and Prevention, China
ClinicalTrials.gov Identifier: NCT01881581     History of Changes
Other Study ID Numbers: CDCPChina001
Study First Received: June 16, 2013
Last Updated: June 19, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention, China:
Therapeutic
Vaccine
HIV
MVA
DNA

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014