NCT00529698

Brief Summary

This Phase I study is 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 healthy, immunologically competent adult subjects without identifiable risk of HIV-1 infection.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_1 hiv-infections

Timeline
Completed

Started Jan 2004

Longer than P75 for phase_1 hiv-infections

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2004

Completed
3.7 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 14, 2007

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2007

Completed
Last Updated

March 1, 2011

Status Verified

July 1, 2007

First QC Date

September 13, 2007

Last Update Submit

February 28, 2011

Conditions

HIV Infections

Keywords

HIVTat proteinPreventative vaccineHealthy volunteersHIV-1/2 uninfectedHIV Preventive Vaccine

Outcome Measures

Primary Outcomes (1)

  • Assessment of safety includes clinical observation and monitoring of haematological, biochemical, virological and immunological parameters. Safety is evaluated by monitoring of volunteers for local and systemic adverse reactions during the trial.

Secondary Outcomes (1)

  • To qualify Tat protein as immunogenic, volunteers are monitored for anti-Tat specific antibodies, anti-Tat proliferative response and in vitro gamma-IFN and IL-4 (or IL-10) production in response to Tat (Elispot).

Study Arms (2)

A

OTHER

Subjects were immunized subcutaneously with Tat, 3 dosage groups (7.5, 15 or 30 micrograms), in association with Alum as adjuvant, or with Saline + Alum, as placebo.

Biological: Biologically active recombinant Tat protein

B

OTHER

Subjects were immunized intradermally with Tat, 3 dosage groups (7.5, 15 or 30 micrograms), or with Saline, as placebo.

Biological: Biologically active recombinant Tat protein

Interventions

Biologically active recombinant Tat proteinBIOLOGICAL
AB

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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 for all the duration of the study;
  • Complete blood count and differential defined as:
  • Hematocrit \>=30% for women, \>= 38% for men
  • Hemoglobin \>= 9.5 g/dL
  • White cell counts \>= 4,000 and \<= 9,500 cells/mm3
  • Total lymphocyte count \>=1000 cells/mm3
  • CD4+ T cell count \> 500 cells/microL based on 2 separate determinations (Hannet, 1992)
  • Platelets (100,000-550,000/ mm3)
  • Differential within institutional normal limits or approval of site physician;
  • Normal ALT (as defined by the range of the clinical site laboratory) and Creatinine (\< 1.6 mg/dl);
  • Normal urine dipstick with esterase and nitrite;
  • Normal thyroid function;
  • Negative ELISA for HIV-1/HIV-2 and HIV-1 viral load (plasma viremia) \< 50 copies/mL within 1 month of immunization;
  • 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.

You may not qualify if:

  • Identifiable high-risk behavior for HIV-1 infection, including a history of injection drug use within 12 months prior to enrollment or higher-risk sexual behavior;
  • History of neoplastic diseases, encephalopathy, neuropathy or unstable CNS pathology, immunodeficiency, autoimmune disease, angina or cardiac arrhythmias, 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 psychotropic drugs;
  • Participation in another experimental protocol within six months prior to 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 cardiovascular disease (e.g. unstable hypersensitive disease needing modification or introduction of an anti-hypersensitive treatment);
  • Use of investigational agents within 90 days prior to study;
  • Receipt of blood products or immunoglobulin in the past 6 months;
  • Prior receipt of HIV-1 vaccine in a previous HIV vaccine trial;
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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 (6)

  • 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: 17117011BACKGROUND

  • 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: 15776379BACKGROUND

  • 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: 10371502BACKGROUND

  • 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: 11085582BACKGROUND

  • 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: 14551888BACKGROUND

  • Ensoli B, Fiorelli V, Ensoli F, Lazzarin A, Visintini R, Narciso P, Di Carlo A, Tripiciano A, Longo O, Bellino S, Francavilla V, Paniccia G, Arancio A, Scoglio A, Collacchi B, Ruiz Alvarez MJ, Tambussi G, Tassan Din C, Palamara G, Latini A, Antinori A, D'Offizi G, Giuliani M, Giulianelli M, Carta M, Monini P, Magnani M, Garaci E. The preventive phase I trial with the HIV-1 Tat-based vaccine. Vaccine. 2009 Dec 11;28(2):371-8. doi: 10.1016/j.vaccine.2009.10.038. Epub 2009 Oct 29.

    PMID: 19879233DERIVED

Related Links

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Barbara Ensoli, MD, PhD

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

    STUDY DIRECTOR

Study Design

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

Study Record Dates

First Submitted

September 13, 2007

First Posted

September 14, 2007

Study Start

January 1, 2004

Study Completion

November 1, 2007

Last Updated

March 1, 2011

Record last verified: 2007-07

Locations

IT(4)