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Safety and Immunogenicity of Recombinant HIV Vaccines for HIV/AIDS

Primary Purpose

Acquired Immunodeficiency Syndrome

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Saline Solution

D-GPEi

M-GPE

About this trial

This is an interventional treatment trial for Acquired Immunodeficiency Syndrome focused on measuring Therapeutic, Vaccine, HIV, MVA, DNA

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept 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.

Sites / Locations

Beijing Ditan Hospital of Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Lower dose DNA or Placebo

Medium dose DNA or Placebo

High dose DNA or Placebo

Lower dose MVA or Placebo

Medium dose MVA or Placebo

High dose MVA or Placebo

Low dose DNA+MVA or Placebo control

High dose DNA+MVA or Placebo control

Arm Description

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01881581

First Posted

June 16, 2013

Last Updated

June 19, 2013

Sponsor

Centers for Disease Control and Prevention, China

Collaborators

Beijing Ditan Hospital, National Institutes for Food and Drug Control, China

1. Study Identification

Unique Protocol Identification Number

NCT01881581

Brief Title

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

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Unknown status

Study Start Date

June 2013 (undefined)

Primary Completion Date

March 2014 (Anticipated)

Study Completion Date

August 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centers for Disease Control and Prevention, China

Collaborators

Beijing Ditan Hospital, National Institutes for Food and Drug Control, China

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acquired Immunodeficiency Syndrome

Keywords

Therapeutic, Vaccine, HIV, MVA, DNA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lower dose DNA or Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Medium dose DNA or Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

High dose DNA or Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Lower dose MVA or Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Medium dose MVA or Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

High dose MVA or Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Low dose DNA+MVA or Placebo control

Arm Type

Experimental

Arm 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

Arm Title

High dose DNA+MVA or Placebo control

Arm Type

Experimental

Arm 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

Intervention Type

Biological

Intervention Name(s)

Saline Solution

Intervention Description

Saline Solution is used as control in all arms.

Intervention Type

Biological

Intervention Name(s)

D-GPEi

Intervention Description

D-GPEi is used in Arm A,B,C,G and H.

Intervention Type

Biological

Intervention Name(s)

M-GPE

Intervention Description

M-GPE is used in Arm D,E,F,G and H

Primary Outcome Measure Information:

Title

Occurrence, intensity and relationship to vaccination of local and systemic adverse events

Description

Time Frame

8 months

Secondary Outcome Measure Information:

Title

Immunogenicity of vaccine

Description

Time Frame

14 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xingwang Li, M.D.

Organizational Affiliation

Beijng Ditan Hospital of Capital Medical University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Rongmeng Jiang, M.D.

Organizational Affiliation

Beijng Ditan Hospital of Capital Medical University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yi Zeng

Organizational Affiliation

National Institute for Viral Disease Control and Prevention, China CDC

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Xia Feng, Ph.D

Organizational Affiliation

National Institute for Viral Disease Control and Prevention, China CDC

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ke Xu, Ph.D

Organizational Affiliation

National Institute for Viral Disease Control and Prevention, China CDC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Ditan Hospital of Capital Medical University

City

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xingwang Li

Phone

15611973658

ditanlxw@yahoo.com.cn

First Name & Middle Initial & Last Name & Degree

Xingwang Li

First Name & Middle Initial & Last Name & Degree

Rongmeng Jiang

12. IPD Sharing Statement

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Safety and Immunogenicity of Recombinant HIV Vaccines for HIV/AIDS

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