Observational Study for the Extended Follow-up of the Patients Enrolled in the Therapeutic Clinical Trial ISS T-002

HIV Infection Clinical Trial

— ISST-002 EF-UP  

Official title:

OBSERVATIONAL STUDY FOR THE EXTENDED FOLLOW-UP OF THE PATIENTS ENROLLED IN THE PHASE II THERAPEUTIC CLINICAL TRIAL ISS T-002

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02118168
• Other study ID #: ISS T-002 EF-UP
• Status: Completed
• Phase: N/A
• First received: April 15, 2014
• Last updated: August 21, 2017
• Start date: September 2013
• Est. completion date: December 2016

Study information

• Verified date: August 2017
• Source: Istituto Superiore di Sanità
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

An observational study to prospectively follow-up the patients enrolled in the ISS T-002 clinical trial up to 132 weeks. The primary endpoint of this study is to evaluate the persistence, in term of frequency, magnitude and quality, of the anti-Tat humoral and cellular immune response in the HIV-1 infected individuals who participated to the ISS T-002 and who have received at least 3 immunizations. The secondary endpoint is to define and validate novel laboratory tests for future efficacy clinical trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: December 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Previous participation in the ISS T-002 trial, having received at least 3 immunizations;

• A follow-up of at least 48 weeks during the ISS T-002 study;

• Availability to participate in the extended follow-up study;

• Signed informed consent.

Exclusion Criteria:

• The absence of any of the above criteria will exclude the subjects from the study.

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Other:
• No intervention
No intervention is foreseen in this Observational Study

Locations

Country	Name	City	State
Italy	Divisione Malattie Infettive - AO Ospedale Policlinico Consorziale	Bari
Italy	Ambulatorio Malattie Infettive - AO Universitaria	Ferrara
Italy	Unità Operativa di Malattie Infettive - Ospedale S.M. Annunziata	Firenze
Italy	Istituto di Malattie Infettive e Tropicali - AO Luigi Sacco	Milano
Italy	U. O. di Malattie Infettive Centro di Ricerca e Cura Patologie HIV correlate - Ospedale San Raffaele	Milano
Italy	Divisione di Malattie Infettive - AO Universitaria Policlinico	Modena
Italy	Divisione di Malattie Infettive Azienda Ospedaliera S. Gerardo	Monza	MB
Italy	U.O.C. Dermatologia Infettiva ed Allergologica - IFO San Gallicano	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Barbara Ensoli, MD, PhD

Country where clinical trial is conducted

Italy, 

References & Publications (14)

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. Review. — View Citation

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, Focà 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. — View Citation

Buttò S, Fiorelli V, Tripiciano A, Ruiz-Alvarez MJ, Scoglio A, Ensoli F, Ciccozzi M, Collacchi B, Sabbatucci M, Cafaro A, Guzmán 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. Epub 2003 Sep 30. — View Citation

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, Buttò 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. — View Citation

Cafaro A, Tripiciano A, Sgadari C, Bellino S, Picconi O, Longo O, Francavilla V, Buttò 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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Buttò 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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, Buttò 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. — View Citation

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, Buttò 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. Epub 2005 Mar 14. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	anti-Tat humoral immune response	The primary endpoint of the study is to evaluate the persistence, in term of frequency, magnitude, and quality of the anti-Tat humoral immune response in HAART-treated patients previously immunize with Tat in the ISS T-002 phase II clinical trial.	Every 3 months, up to 2.5 years
Secondary	Testing of the additional Immunological parameters detailed below as a second line testing	The secondary endpoint of the study is to identify and validate immunological testing for future efficacy vaccine clinical trials, as follows: Lymphoproliferative response to Tat, anti-Tat ?IFN, IL4 and IL2 production; In vitro neutralization of Tat activity (Tat/Env uptake); Lymphocyte subsets; Anti-Tat IgG subclasses; Epitope mapping of anti-Tat IgM and IgG; Anti-HIV regulatory and structural proteins antibodies; ADCC; Neutralization of Tat activity by rescue assay; Neutralization of primary HIV isolates; Anti-CCR5 and Anti-CD4 antibodies; Lymphoproliferative response to Env, mitogens and recall antigens In vitro ?IFN, IL4 and IL2 production in response to Tat (ICS) and to Env (ICS/Elispot); B cells phenotype; Characterization of Treg cells; PBMC ICS for granzyme, perforin, cytokines and chemokines; Th1 and Th2 cytokines and chemokines; Lymphocytes spontaneous cell death; B cell cloning; Characterization of clono-specific antibodies; Serum/plasma determination of sCD4.	Every 3 months, up to 2.5 years
Secondary	Testing of virological parameters detailed below, as a second line testing	The secondary endpoint of the study is to identify and validate virological testing for future efficacy vaccine clinical trials, as follows: HIV-1 plasma viremia (viral RNA copies), HIV-1 sequencing and virus phylogenetic analysis, Genotypic resistance, Viral tropism, Anti-HBV antibodies, HBV antigens (HbsAg, HbeAg), Anti-HCV antibodies and plasma viremia, HHV-8 antibodies and plasma viremia, HIV-1 Proviral DNA copies.	Every 3 months, up to 2.5 years

External Links

•   Link