Immunogenicity and Safety Trial of the HIV-1 Tat Vaccine

NCT00751595 | Completed Phase 2 DMC

• 1 other identifier: ISS T-002
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 11

Brief Summary

The study is a randomized, open label, phase II clinical trial directed at evaluating the immunogenicity (as a primary end-point) and the safety (as a secondary end-point), of the recombinant HIV-1 Tat vaccine in HIV-1 infected adult subjects, anti-Tat antibody negative, HAART-treated with chronic suppressed HIV-1 infection, CD4+ T cell counts \>= 200 cells/microliter, levels of plasma viremia \< 50 copies/ml in the last 6 months prior to the screening and without a history of virologic rebound. The immunogenicity of 3 or 5 immunizations of the two different vaccine doses (7.5 and 30 micrograms) of the Tat vaccine has been evaluated.

Conditions

HIV Infections

Keywords

HIV; Tat protein; Therapeutic vaccine; HAART; HIV Therapeutic Vaccine; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Humoral and cellular immune responses to Tat

  It has been measured by the induction, magnitude and persistence of the humoral and cellular immune responses to Tat and by comparing the immunogenicity of a 3 or 5 immunizations of the 7.5 microg and 30 microg vaccine doses.

  up to 144 weeks

Secondary Outcomes (1)

• The Secondary Endpoint has been focused on adverse events, including any significant change in hematological/biochemical and coagulation laboratory parameters.

  up to 144 weeks

Study Arms (2)

ARM A (Tat Protein 7.5 or 30 microg 5X)

EXPERIMENTAL

Group I: Subjects receiving 5 intradermal immunization with Tat (7.5 microg); Group II: Subjects receiving 5 intradermal immunization with Tat (30 microg).

Biological: Tat protein

ARM B (Tat Protein 7.5 or 30 microg, 3X)

EXPERIMENTAL

Group I: Subjects receiving 3 intradermal immunization with Tat (7.5 microg); Group II: Subjects receiving 3 intradermal immunization with Tat (30 microg)

Biological: Tat protein

Interventions

Tat protein BIOLOGICAL

Biologically active recombinant Tat protein

ARM A (Tat Protein 7.5 or 30 microg 5X); ARM B (Tat Protein 7.5 or 30 microg, 3X)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-55 years
• Anti-Tat antibody negative subjects
• HIV-1 infected subjects under successful HAART treatment with HIV plasma viremia \< 50 copies/ml in the last 6 months prior to the screening
• Subjects with any pre-HAART CD4 nadir;
• CD4+ T cell counts ≥ 200 cells/μl at enrolment;
• Availability for the planned study duration
• Negative pregnancy test for women of childbearing potential (to be performed during the screening phase and just before the immunizations) and use of an acceptable mean of contraception (condom, hormonal or mechanical methods) for one month prior to immunization and for the all duration of the study
• Signed informed consent

You may not qualify if:

• Concomitant AIDS-related opportunistic disease;
• Concomitant neoplastic diseases;
• History of malignant neoplastic diseases \[NOTE: Subjects with history of non malignant neoplastic diseases completely resolved according to the fulfillment of all the specific recovery criteria, in agreement with the current guidelines in medical oncology are eligible\];
• History of encephalopathy, neuropathy or unstable CNS pathology, immunodeficiency, autoimmune disease, angina or cardiac arrhythmias, or any other clinically significant medical problems;
• Any evidence, as judged by the investigator, of unstable cardio-vascular disease (e.g. unstable hypertensive disease needing modification or introduction of an anti-hypertensive treatment);
• Chest radiography showing evidence of active or acute cardiac or pulmonary disease within 6 months prior to study screening visit;
• 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 tuberculosis documented PPD skin test within one year \[NOTE: if the PPD skin test is positive, then a chest x-ray will be done and if no findings consistent with active pulmonary tuberculosis and no indications exist for prophylaxis or treatment, the subject is eligible for participation in this trial\];
• Medical or psychiatric condition which preclude subject compliance with the protocol. Specifically, persons with psychotic disorders, major affective disorders, suicidal ideation are to be excluded;
• Current use of psychotropic drugs prescribed for major psychotic disorders;
• Concomitant participation in any experimental study;
• Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
• Receipt of blood products or immunoglobulin in the past year;
• Previous participation in an HIV-1 vaccine trial (subjects who despite their participation as placebo in a HIV-1 vaccine trial have never been effectively administered with a HIV-1 vaccine are eligible);

Sponsors & Collaborators

• Barbara Ensoli, MD: lead

Study Sites (11)

San Gerardo Hospital

Monza, Milan, 20052, Italy

Location

General Hospital of Bari

Bari, 70124, Italy

Location

Spedali Civili di Brescia

Brescia, 25123, Italy

Location

General Hospital-University of Ferrara

Ferrara, 44100, Italy

Location

A.M. Annunziata Hospital

Florence, 50012, Italy

Location

S.M. Goretti Hospital

Latina, 04100, Italy

Location

San Raffaele Hospital

Milan, 20127, Italy

Location

L. Sacco Hospital

Milan, 20152, Italy

Location

General Hospital-University of Modena

Modena, 41100, Italy

Location

San Gallicano Hospital

Rome, 00144, Italy

Location

Amedeo di Savoia Hospital

Torino, 10149, Italy

Location

Related Publications (14)

• 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

• 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

• 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

• 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

• Monini P, Cafaro A, Srivastava IK, Moretti S, Sharma VA, Andreini C, Chiozzini C, Ferrantelli F, Cossut MR, Tripiciano A, Nappi F, Longo O, Bellino S, Picconi O, Fanales-Belasio E, Borsetti A, Toschi E, Schiavoni I, Bacigalupo I, Kan E, Sernicola L, Maggiorella MT, Montin K, Porcu M, Leone P, Leone P, Collacchi B, Palladino C, Ridolfi B, Falchi M, Macchia I, Ulmer JB, Butto S, Sgadari C, Magnani M, Federico MP, Titti F, Banci L, Dallocchio F, Rappuoli R, Ensoli F, Barnett SW, Garaci E, Ensoli B. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies. PLoS One. 2012;7(11):e48781. doi: 10.1371/journal.pone.0048781. Epub 2012 Nov 13.

  PMID: 23152803 BACKGROUND

• Ensoli B, Fiorelli V, Ensoli F, Lazzarin A, Visintini R, Narciso P, Di Carlo A, Monini P, Magnani M, Garaci E. The therapeutic phase I trial of the recombinant native HIV-1 Tat protein. AIDS. 2008 Oct 18;22(16):2207-9. doi: 10.1097/QAD.0b013e32831392d4.

  PMID: 18832884 BACKGROUND

• 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: 19879233 BACKGROUND

• Bellino S, Francavilla V, Longo O, Tripiciano A, Paniccia G, Arancio A, Fiorelli V, Scoglio A, Collacchi B, Campagna M, Lazzarin A, Tambussi G, Din CT, Visintini R, Narciso P, Antinori A, D'Offizi G, Giulianelli M, Carta M, Di Carlo A, Palamara G, Giuliani M, Laguardia ME, Monini P, Magnani M, Ensoli F, Ensoli B. Parallel conduction of the phase I preventive and therapeutic trials based on the Tat vaccine candidate. Rev Recent Clin Trials. 2009 Sep;4(3):195-204. doi: 10.2174/157488709789957529.

  PMID: 20028332 BACKGROUND

• Longo O, Tripiciano A, Fiorelli V, Bellino S, Scoglio A, Collacchi B, Alvarez MJ, Francavilla V, Arancio A, Paniccia G, Lazzarin A, Tambussi G, Din CT, Visintini R, Narciso P, Antinori A, D'Offizi G, Giulianelli M, Carta M, Di Carlo A, Palamara G, Giuliani M, Laguardia ME, Monini P, Magnani M, Ensoli F, Ensoli B. Phase I therapeutic trial of the HIV-1 Tat protein and long term follow-up. Vaccine. 2009 May 26;27(25-26):3306-12. doi: 10.1016/j.vaccine.2009.01.090. Epub 2009 Feb 7.

  PMID: 19208456 BACKGROUND

• Bellino S, Tripiciano A, Picconi O, Francavilla V, Longo O, Sgadari C, Paniccia G, Arancio A, Angarano G, Ladisa N, Lazzarin A, Tambussi G, Nozza S, Torti C, Foca E, Palamara G, Latini A, Sighinolfi L, Mazzotta F, Di Pietro M, Di Perri G, Bonora S, Mercurio VS, Mussini C, Gori A, Galli M, Monini P, Cafaro A, Ensoli F, Ensoli B. The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression: results of a 3-year cohort study. Retrovirology. 2014 Jun 24;11:49. doi: 10.1186/1742-4690-11-49.

  PMID: 24961156 BACKGROUND

• Ensoli B, Bellino S, Tripiciano A, Longo O, Francavilla V, Marcotullio S, Cafaro A, Picconi O, Paniccia G, Scoglio A, Arancio A, Ariola C, Ruiz Alvarez MJ, Campagna M, Scaramuzzi D, Iori C, Esposito R, Mussini C, Ghinelli F, Sighinolfi L, Palamara G, Latini A, Angarano G, Ladisa N, Soscia F, Mercurio VS, Lazzarin A, Tambussi G, Visintini R, Mazzotta F, Di Pietro M, Galli M, Rusconi S, Carosi G, Torti C, Di Perri G, Bonora S, Ensoli F, Garaci E. Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART. PLoS One. 2010 Nov 11;5(11):e13540. doi: 10.1371/journal.pone.0013540.

  PMID: 21085635 RESULT

• Ensoli B, Cafaro A, Monini P, Marcotullio S, Ensoli F. Challenges in HIV Vaccine Research for Treatment and Prevention. Front Immunol. 2014 Sep 8;5:417. doi: 10.3389/fimmu.2014.00417. eCollection 2014.

  PMID: 25250026 RESULT

• Ensoli F, Cafaro A, Casabianca A, Tripiciano A, Bellino S, Longo O, Francavilla V, Picconi O, Sgadari C, Moretti S, Cossut MR, Arancio A, Orlandi C, Sernicola L, Maggiorella MT, Paniccia G, Mussini C, Lazzarin A, Sighinolfi L, Palamara G, Gori A, Angarano G, Di Pietro M, Galli M, Mercurio VS, Castelli F, Di Perri G, Monini P, Magnani M, Garaci E, Ensoli B. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial. Retrovirology. 2015 Apr 29;12:33. doi: 10.1186/s12977-015-0151-y.

  PMID: 25924841 RESULT

• Cafaro A, Tripiciano A, Sgadari C, Bellino S, Picconi O, Longo O, Francavilla V, Butto S, Titti F, Monini P, Ensoli F, Ensoli B. Development of a novel AIDS vaccine: the HIV-1 transactivator of transcription protein vaccine. Expert Opin Biol Ther. 2015;15 Suppl 1:S13-29. doi: 10.1517/14712598.2015.1021328. Epub 2015 Jun 22.

  PMID: 26096836 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Gene Products, tat

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

Intervention Hierarchy (Ancestors)

Trans-Activators; DNA-Binding Proteins; Proteins; Amino Acids, Peptides, and Proteins; Transcription Factors; Viral Replicase Complex Proteins; Viral Nonstructural Proteins; Viral Proteins; Viral Regulatory and Accessory Proteins

Study Officials

• Barbara Ensoli, MD, PhD

  National AIDS Center (CNAIDS), Istituto Superiore di Sanita', Rome, Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PHD

Study Record Dates

• First Submitted: September 11, 2008
• First Posted: September 12, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 4, 2016

Record last verified: 2016-03

Locations

IT (11)