Phase I Safety and Immunogenicity Vaccine Trial Against HIV/AIDS (ISST-001)

February 28, 2011 updated by: Istituto Superiore di Sanità

A Phase I Safety and Immunogenicity Trial of Recombinant HIV-1 Tat in HIV-1 Infected Adult Volunteers

The development of a vaccine against HIV/AIDS has been primary focused on the structural proteins (Env, Gag) of HIV-1 with the aim of inducing sterilizing immunity by blocking virus entry. Alternative approaches are focused on new vaccine strategies aimed at modifying the virus-host dynamic favouring the establishment of a long-term non-progressing disease status. Such strategies target regulatory proteins that are the first to be expressed after infection and are essential for viral replication, infectivity and pathogenesis. Thus, this approach may be effective for both preventive and therapeutic vaccination strategies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Being a very early viral regulatory protein necessary for viral gene expression, cell-to-cell virus transmission and disease progression, Tat represents a key target protein for the host immune response and an optimal candidate for such a vaccination strategy.

Preclinical studies demonstrated that vaccination with a biologically active Tat protein is safe, elicits a broad and specific immune response and induces a long-term protection against infection. Cross-sectional and longitudinal studies in natural infection suggest that the presence of an anti-Tat humoral immune response correlates with asymptomatic infection and with a slower disease progression while the presence of CD8+ T cell responses to Tat correlate with early virus control both in humans and monkeys. Since the immunogenic regions of Tat are well conserved among the HIV-1 M group, a vaccine based on Tat may be used in different geographic areas of the world.

This Phase I study was directed at evaluating the safety profile (as a primary end-point) and the immunogenicity (as a secondary end-point) of the recombinant HIV-1 Tat vaccine in HIV-1 infected adult volunteers with mild immune deficiency (Clinical category A according to CDC), CD4+ T cell counts 400/mL and levels of plasma viremia < 50,000 copies/mL.

Study Design: Randomized, Double Blind, Placebo Controlled, Safety/Immunogenicity Study.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • San Raffaele Hospital
      • Rome, Italy, 00161
        • University of ROme "La Sapienza"
      • Rome, Italy, 00149
        • Hospital Spallanzani
      • Rome, Italy, 00153
        • San Gallicano Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Negative pregnancy test for women of childbearing potential within 3 days prior to baseline evaluation and use of an acceptable means of contraception (condom, hormonal or mechanical method) for one month prior to immunization and the duration of the study;
  • Clinically asymptomatic HIV-1 infected individuals (CDC Clinical category A), as determined by two positive Enzyme-linked immunosorbent assay (ELISA) and a confirmatory Western Blot;
  • Mean CD4+ T cell count >= 400 cells/microL based on 2 separate determinations, at least 2 weeks apart, within the four weeks pre-study screening period. [Note: If one of the two values is < 400 the patient will be excluded. Patients ever having had a value of CD4+ T cell number < 250 will be excluded];
  • Plasma HIV-1 viremia levels <= 50,000 copies/mL;
  • Complete blood count and differential defined as:
  • Hematocrit >= 30% for women, >= 38% for men
  • Hemoglobin >= 9.5 g/dL
  • White cell counts >= 4,000 cells/mm3
  • Total lymphocyte count >= 1000 cells/mm3
  • Platelets >= 100,000/mm3
  • Differential within institutional normal limits or approval of site physician
  • Normal ALT (as defined by the range of the clinical site laboratories) and Creatinine (<= 1.6 mg/dL);
  • Normal urine dipstick with esterase and nitrite;
  • Normal thyroid function;
  • Availability for follow-up for planned duration of at least 12 months and willing to have further brief evaluations at 24 and 36 months;
  • Signed informed consent.

Exclusion Criteria:

  • History of AIDS-related opportunistic or neoplastic disease;
  • History of encephalopathy, neuropathy, or unstable CNS pathology (HIV or non-HIV related);
  • History of non-HIV related neoplastic diseases, autoimmune diseases, angina or cardiac arthymias, or any other clinically significant medical problems;
  • Chest radiography showing evidence of active or acute cardiac or pulmonary disease;
  • History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1000 U.I./mL;
  • History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g. Steven-Johnson syndrome, bronchospasm, or hypotension);
  • Active syphilis [NOTE. If the serology is documented to be a false positive or due to an adequately treated infection, the volunteer is eligible];
  • Active tuberculosis [NOTE: Volunteers with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring isoniazid (INH) therapy are eligible];
  • Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol. Specifically excluded are persons with psychotic disorders, major affective disorders, suicidal ideation;
  • Current use of psychotrophic drugs;
  • Use of antiretroviral therapy within 3 months of pre-study screening.
  • Use of any experimental HIV therapy or participation in another experimental protocol within three (3) months of pre-study screening;
  • Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
  • Any unstable cardio-vascular disease (e.g unstable hypertensive disease needing modification or introduction of an anti-hypertensive treatment);
  • Live attenuated vaccines within 60 days of study [NOTE: Medically indicated sub-unit or killed vaccines (e.g., influenza, pneumococcal, hepatitis A and B) are not exclusionary, but should be given at least 4 weeks away from HIV immunizations];
  • Receipt of blood products or immunoglobulin in the past year;
  • Prior receipt of HIV-1 vaccine in a previous HIV vaccine trial;
  • Positivity for HBV antigens (HBs Ag, HBe Ag), and HCV, HTLV-I and HTLV-II antibodies;
  • Positivity for HHV-8 antibodies and plasmaviremia (volunteers will be screened for anti-HHV-8 antibodies and positivity confirmed by PCR, only the individuals confirmed positive by PCR will be excluded);
  • Pregnant or lactating women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: A
Subjects were immunized subcutaneously with Tat, 3 dosage groups (7.5, 15 or 30 microgrammi), in association with Alum as adjuvant, or with Saline + Alum, as placebo.
Biological: recombinant HIV-1 Tat protein
Other: B
Subjects were immunized intradermally with Tat, 3 dosage groups (7.5, 15 or 30 microgrammi), or with Saline, as placebo.
Biological: recombinant HIV-1 Tat protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Assessment of product safety included clinical monitoring of volunteers for local and systemic adverse reactions during the course of the trial and monitoring of haematological, biochemical, virological and immunological parameters

Secondary Outcome Measures

Outcome Measure
To qualify Tat protein as immunogenic, volunteers were monitored for anti-Tat specific antibodies (IgM, IgG, IgA), anti-Tat proliferative response and in vitro γIFN and IL-4 production by PBMC before vaccination and in response to Tat vaccine.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Superiore di Sanità

Investigators

  • Study Director: Barbara Ensoli, MD, PhD, National AIDS Center, Istituto Superiore di Sanita, Rome, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Study Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

July 20, 2007

First Submitted That Met QC Criteria

July 20, 2007

First Posted (Estimate)

July 23, 2007

Study Record Updates

Last Update Posted (Estimate)

March 1, 2011

Last Update Submitted That Met QC Criteria

February 28, 2011

Last Verified

July 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISST-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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