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

Purpose

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	Intervention	Phase
HIV Infection	Biological: DermaVir Biological: Placebo Drug: HAART	Phase 2


Study Type:	Observational
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS HIV/AIDS Medicines

U.S. FDA Resources

Further study details as provided by Genetic Immunity:

Primary Outcome Measures:

HIV-specific memory T cells measured as PHPC count [ Time Frame: 9 week ] [ Designated as safety issue: No ]
DermaVir-induced PHPC count compared to Placebo

Secondary Outcome Measures:

HIV-1 RNA [ Time Frame: weeks 16 and 20 ] [ Designated as safety issue: Yes ]
HIV-1 RNA set-point after analytical treatment interruption
CD4+ and CD8+ T cell counts [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]
Adverse Events [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]

Biospecimen Retention: Samples With DNA

peripheral blood mononuclear cells (PBMC) and plasma


Enrollment:	16
Study Start Date:	April 2009
Study Completion Date:	June 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
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

Groups/Cohorts

Assigned Interventions

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

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

Eligibility


Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00918840

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

Additional Information:

Genetic Immunity's homepage This link exits the ClinicalTrials.gov site

Virostatics srl homepage This link exits the ClinicalTrials.gov site

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
Study First Received:	June 8, 2009
Last Updated:	February 7, 2013
Health Authority:	Italy: Ethics Committee

Keywords provided by Genetic Immunity:


HIV Vaccine Immune Therapy DermaVir Treatment experienced

ClinicalTrials.gov processed this record on March 03, 2015

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