Antiretroviral-Sparing Concept With HIV-specific T Cell Precursors With High Proliferative Capacity (PHPC) (PHPC-02)

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

PHPC-02 is a phase II, randomized, placebo-controlled trial designed to investigate whether therapeutic immunization during highly active antiretroviral therapy (HAART) induces elevations of HIV-specific T cell precursors with high proliferative capacity (PHPC) in HIV-1-infected individuals, and whether the quantity of PHPC correlates with the viral load set point following analytical treatment interruption (ATI). Subjects will be randomized to receive either DermaVir Patch (8 subjects per cohort) or DermaVir Patch Placebo (8 subjects per cohort) every four weeks for three applications while receiving maximally suppressive HAART. HAART will be discontinued at Week 9 for an ATI period of 20 weeks.

Condition or disease	Intervention/treatment
HIV Infection	Biological: DermaVir; Biological: Placebo; Drug: HAART

Detailed Description:

16 subjects on maximally suppressive HAART were randomized to receive three doses of either DermaVir or Placebo immunotherapy.

Subjects receive three DermaVir/Placebo treatments over eight weeks (Weeks 0, 4 and 8) while receiving HAART. HAART is discontinued for a 20 week ATI.

Resumption of HAART during ATI is subjects experience:

• A confirmed CD4+ cell decrease by > 50%
• A confirmed CD4+ cell decrease to less than 350 counts/mL
• A confirmed VL increase > 300,000 copies
• Emergence of CDC AIDS related event(s)
• Signs or symptoms of clinically significant immunosuppression
• The subject or the subject's clinician wishes to restart HAART
• The subject becomes pregnant

Study Design

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Actual Enrollment :	16 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Antiretroviral-Sparing Concept: An Exploratory Phase II, Randomized, Single Blind Placebo-Controlled Study to Investigate the Effect of Therapeutic Immunization on the Quantity of HIV-Specific T Cell Precursors During Highly Active Antiretroviral Therapy Followed by Analytical Treatment Interruption
Study Start Date :	April 2009
Actual Primary Completion Date :	June 2011
Actual Study Completion Date :	June 2011

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort	Intervention/treatment
DermaVir + HAART; Dosage: 0.4 mg DNA; Dosage form: 3.2 mL DNA/PEIm nanomedicine; Administration with 4 DermaPrep patches; Frequency: every 4 weeks; Duration: 8 weeks (3 DermaVir treatments)	Biological: DermaVir; DermaVir is a synthetic nanomedicine. The active pharmaceutical ingredient is a single plasmid DNA expressing 15 HIV proteins that assemble to HIV-like particles. DermaVir is topically administered with DermaPrep medical device to target the nanomedicine to Langerhans cells of the skin.These Langerhans cells migrate to the lymph node to induce cytotoxic T cells that can kill HIV-infected cells; Other Name: LC002 Drug: HAART; Three or more antiretroviral drugs that can fully suppress HIV RNA; Other Name: Highly active antiretroviral therapy
Placebo + HAART; Dosage form: 3.2 mL Placebo; Administration with 4 DermaPrep patches; Frequency: every four weeks; Duration: 8 weeks (3 Placebo treatments)	Biological: Placebo; Dextrose/glucose solution; Other Name: LC002 Placebo Drug: HAART; Three or more antiretroviral drugs that can fully suppress HIV RNA; Other Name: Highly active antiretroviral therapy

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. HIV-specific memory T cells measured as PHPC count [ Time Frame: 9 week ]
   DermaVir-induced PHPC count compared to Placebo

Secondary Outcome Measures :

1. HIV-1 RNA [ Time Frame: weeks 16 and 20 ]
   HIV-1 RNA set-point after analytical treatment interruption
2. CD4+ and CD8+ T cell counts [ Time Frame: 20 weeks ]
3. Adverse Events [ Time Frame: 20 weeks ]

Biospecimen Retention:   Samples With DNA

peripheral blood mononuclear cells (PBMC) and plasma

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Primary care clinic

Criteria

Main inclusion Criteria:

• HIV-1 infection
• On a non-hydroxyurea based HAART for at least one year
• Pre-HAART CD4 nadir > 250 cells/mm3
• Pre-HAART viral load > 5,000 copies/mL
• Undetectable viral load for the six month period preceding the study
• CD4 T-cell count >500 cells/mm3 for the six month period preceding the study

Main exclusion Criteria:

• No skin disease
• No hypersensitivity to adhesive tape or Tegaderm
• No history of keloid
• No history of vitiligo, melasma, skin cancer
• No tattoos or changes in pigment at the skin treatment sites
• No autoimmune diseases
• No hepatitis B, C coinfections

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Italy
IRCCS Policlinico S. Matteo
Pavia, Italy, 27100

Sponsors and Collaborators

Genetic Immunity

ViroStatics srl

IRCCS Policlinico S. Matteo

Investigators

Principal Investigator:	Renato Maserati, MD	IRCCS Policlinico S. Matteo
Study Chair:	Franco Lori, MD	ViroStatics srl

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Genetic Immunity's homepage 

Virostatics srl homepage 

Publications:

Lisziewicz J, Tőke ER. Nanomedicine applications towards the cure of HIV. Nanomedicine. 2013 Jan;9(1):28-38. doi: 10.1016/j.nano.2012.05.012. Epub 2012 May 30. Review.

Lisziewicz J, Bakare N, Calarota SA, Bánhegyi D, Szlávik J, Ujhelyi E, Tőke ER, Molnár L, Lisziewicz Z, Autran B, Lori F. Single DermaVir immunization: dose-dependent expansion of precursor/memory T cells against all HIV antigens in HIV-1 infected individuals. PLoS One. 2012;7(5):e35416. doi: 10.1371/journal.pone.0035416. Epub 2012 May 9.

Lőrincz O, Tőke ER, Somogyi E, Horkay F, Chandran PL, Douglas JF, Szebeni J, Lisziewicz J. Structure and biological activity of pathogen-like synthetic nanomedicines. Nanomedicine. 2012 May;8(4):497-506. doi: 10.1016/j.nano.2011.07.013. Epub 2011 Aug 10.

Somogyi E, Xu J, Gudics A, Tóth J, Kovács AL, Lori F, Lisziewicz J. A plasmid DNA immunogen expressing fifteen protein antigens and complex virus-like particles (VLP+) mimicking naturally occurring HIV. Vaccine. 2011 Jan 17;29(4):744-53. doi: 10.1016/j.vaccine.2010.11.019. Epub 2010 Nov 23.

Calarota SA, Foli A, Maserati R, Baldanti F, Paolucci S, Young MA, Tsoukas CM, Lisziewicz J, Lori F. HIV-1-specific T cell precursors with high proliferative capacity correlate with low viremia and high CD4 counts in untreated individuals. J Immunol. 2008 May 1;180(9):5907-15.

Cristillo AD, Lisziewicz J, He L, Lori F, Galmin L, Trocio JN, Unangst T, Whitman L, Hudacik L, Bakare N, Whitney S, Restrepo S, Suschak J, Ferrari MG, Chung HK, Kalyanaraman VS, Markham P, Pal R. HIV-1 prophylactic vaccine comprised of topical DermaVir prime and protein boost elicits cellular immune responses and controls pathogenic R5 SHIV162P3. Virology. 2007 Sep 15;366(1):197-211. Epub 2007 May 11.

Calarota SA, Weiner DB, Lori F, Lisziewicz J. Induction of HIV-specific memory T-cell responses by topical DermaVir vaccine. Vaccine. 2007 Apr 20;25(16):3070-4. Epub 2007 Jan 22.

Lori F, Foli A, Lisziewicz J. Stopping HAART temporarily in the absence of virus rebound: exploring new HIV treatment options. Curr Opin HIV AIDS. 2007 Jan;2(1):14-20. doi: 10.1097/COH.0b013e328011aad6.

Xu JQ, Lori F, Lisziewicz J. CD4+ T cell-mediated presentation of non-infectious HIV-1 virion antigens to HIV-specific CD8+ T cells. Chin Med J (Engl). 2006 Oct 5;119(19):1629-38.

Lisziewicz J, Trocio J, Whitman L, Varga G, Xu J, Bakare N, Erbacher P, Fox C, Woodward R, Markham P, Arya S, Behr JP, Lori F. DermaVir: a novel topical vaccine for HIV/AIDS. J Invest Dermatol. 2005 Jan;124(1):160-9.

Lisziewicz J, Trocio J, Xu J, Whitman L, Ryder A, Bakare N, Lewis MG, Wagner W, Pistorio A, Arya S, Lori F. Control of viral rebound through therapeutic immunization with DermaVir. AIDS. 2005 Jan 3;19(1):35-43.

Lori F, Kelly LM, Lisziewicz J. APC-targeted immunization for the treatment of HIV-1. Expert Rev Vaccines. 2004 Aug;3(4 Suppl):S189-98. Review.

Foli A, Maserati R, Barasolo G, Castelli F, Tomasoni L, Migliorino M, Maggiolo F, Pan A, Paolucci S, Scudeller L, Tinelli C, D'Aquila R, Lisziewicz J, Lori F. Strategies to decrease viral load rebound, and prevent loss of CD4 and onset of resistance during structured treatment interruptions. Antivir Ther. 2004 Feb;9(1):123-32.

Lisziewicz J, Bakare N, Lori F. Therapeutic vaccination for future management of HIV/AIDS. Vaccine. 2003 Jan 30;21(7-8):620-3. Review.

Responsible Party:	Genetic Immunity
ClinicalTrials.gov Identifier:	NCT00918840 History of Changes
Other Study ID Numbers:	PHPC-02; 2008-003765-11 ( EudraCT Number )
First Posted:	June 11, 2009
Last Update Posted:	February 8, 2013
Last Verified:	February 2013

Keywords provided by Genetic Immunity:

HIV; Vaccine; Immune Therapy; DermaVir; Treatment experienced

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases	Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases