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HIV InfectionsPhase 2ISS T-002NCT00751595

Immunogenicity and Safety Trial of the HIV-1 Tat Vaccine

A Phase 2 study testing Tat protein in people with HIV Infections, run by Barbara Ensoli, MD at 11 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
HIV Infections
What is being tested?
Tat protein
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
168 participants
Where
11 sitesItaly
Study dates
Sep 2008to Dec 2012
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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;
Show all 19Show fewer
  • 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;
  • Live attenuated vaccines within 60 days of study inclusion [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;
  • 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);
  • Drug and/or alcohol abuse;
  • Use in the last 6 months or concomitant use of anti CCR5 inhibitors and/or integrase inhibitors and/or fusion inhibitors;
  • Pregnant or lactating women

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Italy11 sites

  • General Hospital of Bari

    Bari, 70124

  • Spedali Civili di Brescia

    Brescia, 25123

  • General Hospital-University of Ferrara

    Ferrara, 44100

  • A.M. Annunziata Hospital

    Florence, 50012

  • S.M. Goretti Hospital

    Latina, 04100

  • San Raffaele Hospital

    Milan, 20127

  • L. Sacco Hospital

    Milan, 20152

  • General Hospital-University of Modena

    Modena, 41100

  • San Gerardo Hospital

    Monza, Milan, 20052

  • San Gallicano Hospital

    Rome, 00144

  • Amedeo di Savoia Hospital

    Torino, 10149

Other trials in Italy

About this study

Official title: A Phase II Randomized, Open Label, Immunogenicity and Safety Trial of the Vaccine Based on the Recombinant Biologically Active HIV-1 Tat Protein in Anti-Tat Negative HIV-1 Infected HAART-treated Adult Subjects.

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.

Read the detailed description

This phase II clinical trial was directed at evaluating the immunogenicity and the safety of the HIV-1 Tat protein-based vaccine. Anti-Tat antibody negative, HIV-1 positive subjects treated successfully with HAART have been screened and recruited for a 48-weeks study, including a period of 16 or 8 weeks treatment phase and a period of 32 or 40 weeks follow-up phase, in arm A or Arm B, respectively. One hundred sixty-eight subjects have been randomized 1:1:1:1 to one of the 2 arms (Arm A and Arm B) and each arm has been divided in the following groups:

Arm A - Group I: 5 immunizations with Tat (7.5 microg) at weeks 0, 4, 8, 12, 16; Arm A - Group II: 5 immunizations with Tat (30 microg) at weeks 0, 4, 8, 12, 16; Arm B - Group I: 3 immunizations with Tat (7.5 microg) at weeks 0, 4, 8; Arm B - Group II: 3 immunizations with Tat (30 microg) at weeks 0, 4, 8.

Four vaccination regimens have been tested by intradermal administration of the Tat vaccine at two different doses (7.5 microg or 30 microg) in 5 or 3 immunizations.

Conditions
HIV Infections
Being tested
Tat protein
Keywords
HIV, Tat protein, Therapeutic vaccine, HAART, HIV Therapeutic Vaccine, Treatment Experienced
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tat proteinBiological

    Biologically active recombinant Tat protein

Study groups in NCT00751595
Study groupRoleWhat they receive
ARM A (Tat Protein 7.5 or 30 microg 5X)ExperimentalGroup I: Subjects receiving 5 intradermal immunization with Tat (7.5 microg); Group II: Subjects receiving 5 intradermal immunization with Tat (30 microg).
Receives: Biological: Tat protein
ARM B (Tat Protein 7.5 or 30 microg, 3X)ExperimentalGroup I: Subjects receiving 3 intradermal immunization with Tat (7.5 microg); Group II: Subjects receiving 3 intradermal immunization with Tat (30 microg)
Receives: Biological: Tat protein

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 144 weeks

Secondary outcomes (1)

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

    Measured: up to 144 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionJun 2012
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
168 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00751595
Sponsor's protocol ID
ISS T-002
Acronym
ISS T-002
Status last verified
Mar 2016
First submitted
11 Sep 2008
Last updated
4 Mar 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 14551888

  • 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.

    PubMed 11085582

  • 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.

    PubMed 15776379

  • 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.

    PubMed 17117011

  • 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.

    PubMed 23152803

  • 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.

    PubMed 18832884

  • 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.

    PubMed 19879233

  • 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.

    PubMed 20028332

  • 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.

    PubMed 19208456

  • 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.

    PubMed 24961156

  • 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.

    PubMed 21085635

  • 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.

    PubMed 25250026

  • 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.

    PubMed 25924841

  • 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.

    PubMed 26096836

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tat protein in people with HIV Infections, run by Barbara Ensoli, MD at 11 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Humoral and cellular immune responses to Tat (time frame: up to 144 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00751595, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2016.

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