Phase I Safety and Immunogenicity Vaccine Trial Against HIV/AIDS

NCT00505401 | Completed Phase 1 DMC

• 1 other identifier: ISST-001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV; Tat protein; HIV Therapeutic Vaccine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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.

Study Arms (2)

A

OTHER

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

B

OTHER

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

Interventions

recombinant HIV-1 Tat protein BIOLOGICAL

A; B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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);
• Receipt of blood products or immunoglobulin in the past year;

Sponsors & Collaborators

• Istituto Superiore di Sanità: lead

Study Sites (4)

San Raffaele Hospital

Milan, 20132, Italy

Location

Hospital Spallanzani

Rome, 00149, Italy

Location

San Gallicano Hospital

Rome, 00153, Italy

Location

University of Rome "La Sapienza"

Rome, 00161, Italy

Location

Related Publications (5)

• Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Butto S, Monini P, Magnani M, Caputo A, Garaci E. Candidate HIV-1 Tat vaccine development: from basic science to clinical trials. AIDS. 2006 Nov 28;20(18):2245-61. doi: 10.1097/QAD.0b013e3280112cd1. No abstract available.

  PMID: 17117011 BACKGROUND

• Rezza G, Fiorelli V, Dorrucci M, Ciccozzi M, Tripiciano A, Scoglio A, Collacchi B, Ruiz-Alvarez M, Giannetto C, Caputo A, Tomasoni L, Castelli F, Sciandra M, Sinicco A, Ensoli F, Butto S, Ensoli B. The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters. J Infect Dis. 2005 Apr 15;191(8):1321-4. doi: 10.1086/428909. Epub 2005 Mar 14.

  PMID: 15776379 BACKGROUND

• Cafaro A, Caputo A, Fracasso C, Maggiorella MT, Goletti D, Baroncelli S, Pace M, Sernicola L, Koanga-Mogtomo ML, Betti M, Borsetti A, Belli R, Akerblom L, Corrias F, Butto S, Heeney J, Verani P, Titti F, Ensoli B. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med. 1999 Jun;5(6):643-50. doi: 10.1038/9488.

  PMID: 10371502 BACKGROUND

• Cafaro A, Caputo A, Maggiorella MT, Baroncelli S, Fracasso C, Pace M, Borsetti A, Sernicola L, Negri DR, Ten Haaft P, Betti M, Michelini Z, Macchia I, Fanales-Belasio E, Belli R, Corrias F, Butto S, Verani P, Titti F, Ensoli B. SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine. J Med Primatol. 2000 Aug;29(3-4):193-208. doi: 10.1034/j.1600-0684.2000.290313.x.

  PMID: 11085582 BACKGROUND

• Butto S, Fiorelli V, Tripiciano A, Ruiz-Alvarez MJ, Scoglio A, Ensoli F, Ciccozzi M, Collacchi B, Sabbatucci M, Cafaro A, Guzman CA, Borsetti A, Caputo A, Vardas E, Colvin M, Lukwiya M, Rezza G, Ensoli B; Tat Multicentric Study Group. Sequence conservation and antibody cross-recognition of clade B human immunodeficiency virus (HIV) type 1 Tat protein in HIV-1-infected Italians, Ugandans, and South Africans. J Infect Dis. 2003 Oct 15;188(8):1171-80. doi: 10.1086/378412. Epub 2003 Sep 30.

  PMID: 14551888 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Barbara Ensoli, MD, PhD

  National AIDS Center, Istituto Superiore di Sanità, Rome, Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 20, 2007
• First Posted: July 23, 2007
• Study Start: December 1, 2003
• Study Completion: November 1, 2007
• Last Updated: March 1, 2011

Record last verified: 2007-07

Locations

IT (4)