A Phase I Safety and Immunogenicity Preventive Vaccine Trial Based on the HIV-1 Tat and V2-deleted Env Proteins (ISS P-002)

NCT01441193 | Terminated Phase 1 DMC

• 1 other identifier: ISS P-002
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

This Phase I study was directed at evaluating the safety profile and the immunogenicity of the vaccination with recombinant HIV-1 Tat and V2-deleted Env (delta-V2 Env) proteins administered in association in healthy, immunologically competent adults, compared to delta-V2 Env or Tat alone.

Conditions

HIV Infection

Keywords

HIV; preventive vaccine; Tat; Env

Outcome Measures

Primary Outcomes (1)

• Safety and immunogenicity

  To qualify the vaccine candidate as safe and immunogenic by evaluating the number of local and systemic adverse events, including any significant change in hematological/biochemical/coagulation laboratory parameters, and the frequency of anti-Tat and anti-delta-V2 Env humoral and cellular immune responses

  up to week 68

Study Arms (4)

HIV-1 Tat/delta-V2 Env combined vaccine

EXPERIMENTAL

Tat 7.5 microg and delta-V2 Env 100 microg associated proteins administered i.d. (priming) at week 0, 4 and 8 or i.m. (boosting) at weeks 24 and 36

Biological: HIV-1 Tat/delta-V2 Env combined vaccine

HIV-1 delta-V2 Env vaccine

ACTIVE COMPARATOR

delta-V2 Env 100 microg administered i.d. (priming) at week 0, 4 and 8 or i.m. (boosting) at week 24 and 36

Biological: HIV-1 delta-V2 Env vaccine

HIV-1 Tat vaccine 7.5 microg

ACTIVE COMPARATOR

Tat 7.5 microg administered i.d. (priming) at week 0, 4 and 8 or i.m. (boosting) at week 24 and 36

Biological: HIV-1 Tat vaccine 7.5 microg

HIV-1 Tat vaccine 30 microg

ACTIVE COMPARATOR

Tat 30 microg administered i.d. at week 0, 4 and 8

Biological: HIV-1 Tat vaccine 30 microg

Interventions

HIV-1 Tat/delta-V2 Env combined vaccine BIOLOGICAL

HIV-1 Tat/delta-V2 Env combined vaccine

HIV-1 delta-V2 Env vaccine BIOLOGICAL

HIV-1 delta-V2 Env vaccine

HIV-1 Tat vaccine 7.5 microg BIOLOGICAL

HIV-1 Tat vaccine 7.5 microg

HIV-1 Tat vaccine 30 microg BIOLOGICAL

HIV-1 Tat vaccine 30 microg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 to 55 years;
• Negative blood pregnancy test for women of childbearing potential at screening evaluation (a urine dipstick test will be repeated just before each vaccination), and use of an acceptable mean of contraception by both men and women, since one month prior to immunization (only for women) and until at least 6 months after the last immunization;
• Blood pressure, heart rate and ECG within normal ranges or with mild alterations acknowledged as non clinically significant by the site clinician;
• Haematological and biochemical parameters within the clinical site normal ranges or with mild alterations acknowledged by the site clinician as non clinically significant;
• Normal urine dipstick with esterase and nitrite;
• Normal thyroid function;
• Negative for HIV infection and for anti-Tat antibodies;
• Good physical and mental health status;
• Availability for the planned study duration;
• Signed informed consent.

You may not qualify if:

• Concomitant neoplastic diseases;
• History of malignant neoplastic diseases;
• History of encephalopathy, neuropathy or unstable CNS pathology, immunodeficiency, autoimmune disease, angina or cardiac arrhythmias, or any other clinically significant medical problems;
• History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1,000 U.I./mL;
• History of serious allergic reaction to any substance, requiring hospitalization or emergency medical care;
• Chest radiography showing evidence of active or acute cardiac or pulmonary disease;
• Any unstable cardiovascular disease;
• Active syphilis by TPHA and RPR tests \[NOTE: If the serology is documented to be a false positive or due to an adequately treated infection, the volunteer is eligible\];
• Active tuberculosis by cutaneous TB diagnostic test \[NOTE: Volunteers with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring specific therapy are eligible\];
• Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol. Persons with psychotic disorders, major affective disorders or suicidal ideation are specifically excluded;
• Current use of psychotropic drugs;
• Drug and/or alcohol abuse;
• Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
• Use of investigational agents within 90 days prior to study entry;
• Participation in another experimental protocol within 6 months prior to pre-study screening;

Sponsors & Collaborators

• Barbara Ensoli, MD: lead
• Novartis Vaccines: collaborator

Study Sites (3)

Policlinico di Modena, Divisione di Malattie Infettive

Modena, 41100, Italy

Location

Azienda Ospedaliera San Gerardo, Divisione di Malattie Infettive

Monza, 20052, Italy

Location

IFO - S. Gallicano, Dermatologia Infettiva

Rome, 00153, Italy

Location

Related Publications (13)

• 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 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

• 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

• Caputo A, Gavioli R, Bellino S, Longo O, Tripiciano A, Francavilla V, Sgadari C, Paniccia G, Titti F, Cafaro A, Ferrantelli F, Monini P, Ensoli F, Ensoli B. HIV-1 Tat-based vaccines: an overview and perspectives in the field of HIV/AIDS vaccine development. Int Rev Immunol. 2009;28(5):285-334. doi: 10.1080/08830180903013026.

  PMID: 19811313 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

• 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

• Barnett SW, Srivastava IK, Ulmer JB, Donnelly JJ, Rappuoli R. Development of V2-deleted trimeric envelope vaccine candidates from human immunodeficiency virus type 1 (HIV-1) subtypes B and C. Microbes Infect. 2005 Nov;7(14):1386-91. doi: 10.1016/j.micinf.2005.07.018. Epub 2005 Sep 20.

  PMID: 16275150 BACKGROUND

• Ensoli B, Cafaro A, Caputo A, Fiorelli V, Ensoli F, Gavioli R, Ferrantelli F, Cara A, Titti F, Magnani M. Vaccines based on the native HIV Tat protein and on the combination of Tat and the structural HIV protein variant DeltaV2 Env. Microbes Infect. 2005 Nov;7(14):1392-9. doi: 10.1016/j.micinf.2005.07.016. Epub 2005 Sep 15.

  PMID: 16243561 BACKGROUND

• Caputo A, Brocca-Cofano E, Castaldello A, Voltan R, Gavioli R, Srivastava IK, Barnett SW, Cafaro A, Ensoli B. Characterization of immune responses elicited in mice by intranasal co-immunization with HIV-1 Tat, gp140 DeltaV2Env and/or SIV Gag proteins and the nontoxicogenic heat-labile Escherichia coli enterotoxin. Vaccine. 2008 Feb 26;26(9):1214-27. doi: 10.1016/j.vaccine.2007.12.030. Epub 2008 Jan 15.

  PMID: 18243435 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, 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

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

  Istituto Superiore di Sanità

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: September 26, 2011
• First Posted: September 27, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: March 4, 2016

Record last verified: 2016-03

Locations

IT (3)