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

NCT00918840 | Completed DMC

• 2 other identifiers: PHPC-022008-003765-11
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection

Keywords

HIV; Vaccine; Immune Therapy; DermaVir; Treatment experienced

Outcome Measures

Primary Outcomes (1)

• HIV-specific memory T cells measured as PHPC count

  DermaVir-induced PHPC count compared to Placebo

  9 week

Secondary Outcomes (3)

• HIV-1 RNA

  weeks 16 and 20

• CD4+ and CD8+ T cell counts

  20 weeks

• Adverse Events

  20 weeks

Study Arms (2)

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; Drug: HAART

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; Drug: HAART

Interventions

DermaVir BIOLOGICAL

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

Also known as: LC002

DermaVir + HAART

Placebo BIOLOGICAL

Dextrose/glucose solution

Also known as: LC002 Placebo

Placebo + HAART

HAART DRUG

Three or more antiretroviral drugs that can fully suppress HIV RNA

Also known as: Highly active antiretroviral therapy

DermaVir + HAART; Placebo + HAART

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Primary care clinic

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genetic Immunity: lead
• ViroStatics srl: collaborator
• Fondazione IRCCS Policlinico San Matteo di Pavia: collaborator

Study Sites (1)

IRCCS Policlinico S. Matteo

Pavia, 27100, Italy

Location

Related Publications (14)

• Lisziewicz J, Toke 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.

  PMID: 22659241 BACKGROUND

• Lisziewicz J, Bakare N, Calarota SA, Banhegyi D, Szlavik J, Ujhelyi E, Toke ER, Molnar 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.

  PMID: 22590502 BACKGROUND

• Lorincz O, Toke 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.

  PMID: 21839051 BACKGROUND

• Somogyi E, Xu J, Gudics A, Toth J, Kovacs 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.

  PMID: 21109034 BACKGROUND

• 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. doi: 10.4049/jimmunol.180.9.5907.

  PMID: 18424710 BACKGROUND

• 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. doi: 10.1016/j.virol.2007.04.012. Epub 2007 May 11.

  PMID: 17499328 BACKGROUND

• 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. doi: 10.1016/j.vaccine.2007.01.024. Epub 2007 Jan 22.

  PMID: 17292518 BACKGROUND

• 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.

  PMID: 19372860 BACKGROUND

• 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.

  PMID: 17042976 BACKGROUND

• 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. doi: 10.1111/j.0022-202X.2004.23535.x.

  PMID: 15654970 BACKGROUND

• 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. doi: 10.1097/00002030-200501030-00004.

  PMID: 15627031 BACKGROUND

• 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. doi: 10.1586/14760584.3.4.s189.

  PMID: 15285717 BACKGROUND

• 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.

  PMID: 15040544 BACKGROUND

• Lisziewicz J, Bakare N, Lori F. Therapeutic vaccination for future management of HIV/AIDS. Vaccine. 2003 Jan 30;21(7-8):620-3. doi: 10.1016/s0264-410x(02)00569-8.

  PMID: 12531329 BACKGROUND

Related Links

• Genetic Immunity's homepage
• Virostatics srl homepage

Biospecimen

Retention: SAMPLES WITH DNA

peripheral blood mononuclear cells (PBMC) and plasma

MeSH Terms

Conditions

HIV Infections

Interventions

DermaVir; Antiretroviral Therapy, Highly Active

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

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Study Officials

• Renato Maserati, MD

  Fondazione IRCCS Policlinico San Matteo di Pavia

  PRINCIPAL INVESTIGATOR

• Franco Lori, MD

  ViroStatics srl

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2009
• First Posted: June 11, 2009
• Study Start: April 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: February 8, 2013

Record last verified: 2013-02

Locations

IT (1)