Safety, Tolerability and Immune Response to LC002, an Experimental Therapeutic Vaccine, in Adults Receiving HAART

NCT00270205 | Completed Phase 1 Results DMC

• 3 other identifiers: A517610126ACTG A5176
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

LC002 is an experimental therapeutic vaccine designed to boost the immune response of people infected with HIV. The purpose of this study was to determine the safety and tolerability of and immune response to LC002 in HIV-1-infected adults who are currently receiving anti-HIV treatment.

Conditions

HIV Infections

Keywords

Treatment Experienced; HIV Therapeutic Vaccine

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Primary Safety Endpoint

  Primary safety endpoint is defined as occurrence of at least one grade 3 or higher adverse event, including signs/symptoms, lab toxicities, and/or clinical events that is possibly or definitely related to study treatment. Event's relationship to the study treatment was determined by the protocol core team, including site clinicians on the team, blinded to the treatment arm. Adverse events solely attributed to an allergic reaction to the adhesive of the tape used to adhere the vaccination patch to the skin and not the vaccine itself were not used in determination of the primary safety endpoint.

  From start of study vaccination to 28 days after the last study vaccination

Secondary Outcomes (26)

• Time-averaged Area Under the Curve (AUC) of CD4+ T-cell Count in PBMCs

  From start of study vaccination to week 61

• Time-averaged AUC of CD8+ T-cell Count in PBMCs

  From start of study vaccination to week 61

• Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by Taking the Mean of the Number of Spot-forming Cells/10^6 PBMCs Observed in Each PHPC Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.

  From start of study vaccination to week 37

• Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by the Number of Spot-forming Cells/10^6 PBMCs Observed in Each PHPC Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.

  From start of study vaccination to week 37

• Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by Taking the Mean of the Number of Spot-forming Cells/10^6 PBMCs Observed in Each ELISPOT Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.

  From start of study vaccination to week 37

Other Outcomes (1)

• Breadth of HIV-1-specific Immune Response, as Determined by the Number of Overlapping HIV-1 Peptides for Which the ELISPOT Assay for IFN-gamma Production is Observed to Have Five or More Spot-forming Cells/ 10^5 PBMCs

  From start of study vaccination to week 24

Study Arms (6)

A: 0.1 mg DNA/participant vaccination at weeks 1,7,13

EXPERIMENTAL

Participants receiving three separate low-dose vaccinations of LC002 (0.1 mg DNA/participant, 0.8 ml total, administered over two skin sites \[on the left and right upper back\] of 80 cm\^2 each, 0.4 ml/site) at weeks 1, 7, and 13.

Biological: LC002 standard vaccination

B

EXPERIMENTAL

Participants receiving three separate vaccinations of LC002 placebo (0.8 ml total, administered over two skin sites \[on the left and right upper back\] of 80 cm\^2 each, 0.4 ml/site) at weeks 1, 7, and 13.

Biological: LC002 placebo vaccination

C: 0.4 mg DNA/participant vaccination at weeks 1, 7, 13

EXPERIMENTAL

Participants receiving three separate high-dose vaccinations of LC002 (0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites \[on the left and right upper back and left and right upper ventral thigh\] of 80 cm\^2 each, 0.8 ml/site) at weeks 1, 7, and 13.

Biological: LC002 high-dose vaccination

D

EXPERIMENTAL

Participants receiving three separate vaccinations of LC002 placebo (3.2 ml total, administered over four skin sites \[on the left and right upper back and left and right upper ventral thigh\] of 80 cm\^2 each, 0.8 ml/site) at weeks 1, 7, and 13.

Biological: LC002 placebo vaccination

E: 0.4 mg DNA/participant vaccination at weeks 0,1,6,7,12,13

EXPERIMENTAL

Participants receiving six separate high-dose vaccinations of LC002 (0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites \[on the left and right upper back and left and right upper ventral thigh\] of 80 cm\^2 each, 0.8 ml/site) at study entry and weeks 1, 6, 7, 12, and 13.

Biological: LC002 high-dose vaccination

F

EXPERIMENTAL

Participants receiving six separate vaccinations of LC002 placebo (3.2 ml total, administered over four skin sites \[on the left and right upper back and left and right upper ventral thigh\] of 80 cm\^2 each, 0.8 ml/site) at study entry and weeks 1, 6, 7, 12, and 13.

Biological: LC002 placebo vaccination

Interventions

LC002 standard vaccination BIOLOGICAL

0.1 mg DNA/participant, 0.8 ml total administered subcutaneously

A: 0.1 mg DNA/participant vaccination at weeks 1,7,13

LC002 high-dose vaccination BIOLOGICAL

0.4 mg DNA/participant, 3.2 ml total administered subcutaneously

C: 0.4 mg DNA/participant vaccination at weeks 1, 7, 13; E: 0.4 mg DNA/participant vaccination at weeks 0,1,6,7,12,13

LC002 placebo vaccination BIOLOGICAL

Placebo vaccination administered subcutaneously

B; D; F

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1-infected
• On a stable HAART regimen without changes or interruptions for more than 4 consecutive days for at least 12 weeks prior to study entry. Patients must be currently taking regimens containing drugs of at least two different classes.
• Two readings of plasma HIV-1 viral load of less than 50 copies/ml within 30 days prior to study entry. More information on this criterion can be found in the protocol.
• CD4 count greater than 350 cells/mm\^3 within 12 weeks prior to study entry
• Lowest CD4 count greater than 250 cells/mm\^3 at any time prior to study entry
• Willing to use acceptable forms of contraception
• Karnofsky performance score 90 or higher obtained within 30 days prior to study entry

You may not qualify if:

• HIV-1 viral load greater than 500 copies/ml within the 24 weeks prior to study entry
• History of or current active skin disease (e.g., atopic dermatitis, psoriasis) or any chronic autoimmune disease (e.g., Graves' disease). Participants with minor, localized skin conditions that, in the opinion of the investigator, do not represent a safety concern, are not excluded.
• Treatment with topical corticosteroids at the proposed vaccination sites (Cohort 1: left and right upper back; Cohorts 2 and 3: left and right upper back and left and right upper ventral thigh) within 2 weeks of study entry
• Excessive exposure to the sun (e.g., sunbathing, tanning bed) within 2 weeks prior to study entry
• Laser hair removal within 2 weeks prior to study entry
• Use of any local skin treatments (e.g., topical/chemical hair removal, ointments, possible irritants) to the targeted vaccination sites within 7 days prior to study entry
• History of diabetes or bleeding disorders
• Previous CDC Category C event. More information on this criterion can be found in the protocol.
• Use of immunomodulating therapy, including cyclosporine, IgG-containing products, interleukins, interferons, or systemic glucocorticosteroids (including those inhaled) within 6 months prior to study entry
• Exposure to an experimental HIV vaccine within 6 months prior to study entry
• Any vaccine within 30 days prior to study entry
• Investigational products within 12 weeks prior to study entry
• Allergy or sensitivity to study vaccine products, adhesives, or polyester
• Current drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study
• Serious illness requiring systemic treatment and/or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (5)

Univ. of California Davis Med. Ctr., ACTU

Sacramento, California, 95814, United States

Location

Chicago Children's CRS

Chicago, Illinois, 60614, United States

Location

Case CRS

Cleveland, Ohio, 44106-5083, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109-1998, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

Related Publications (13)

• 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, Trocio J, Bakare N, Kelly LM, Lisziewicz J. DermaVir, a novel HIV immunisation technology. Vaccine. 2005 Mar 18;23(17-18):2030-4. doi: 10.1016/j.vaccine.2005.01.004.

  PMID: 15755566 BACKGROUND

• Lori F, Weiner DB, Calarota SA, Kelly LM, Lisziewicz J. Cytokine-adjuvanted HIV-DNA vaccination strategies. Springer Semin Immunopathol. 2006 Nov;28(3):231-8. doi: 10.1007/s00281-006-0047-y. Epub 2006 Oct 20.

  PMID: 17053912 BACKGROUND

• Rajcani J, Mosko T, Rezuchova I. Current developments in viral DNA vaccines: shall they solve the unsolved? Rev Med Virol. 2005 Sep-Oct;15(5):303-25. doi: 10.1002/rmv.467.

  PMID: 15906276 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

• 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

• Toke ER, Lorincz O, Somogyi E, Lisziewicz J. Rational development of a stable liquid formulation for nanomedicine products. Int J Pharm. 2010 Jun 15;392(1-2):261-7. doi: 10.1016/j.ijpharm.2010.03.048. Epub 2010 Mar 25.

  PMID: 20347027 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

• 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, Rosenberg E, Lieberman J, Jessen H, Lopalco L, Siliciano R, Walker B, Lori F. Control of HIV despite the discontinuation of antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1683-4. doi: 10.1056/NEJM199905273402114. No abstract available.

  PMID: 10348681 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

• Gudmundsdotter L, Wahren B, Haller BK, Boberg A, Edback U, Bernasconi D, Butto S, Gaines H, Imami N, Gotch F, Lori F, Lisziewicz J, Sandstrom E, Hejdeman B. Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial. Vaccine. 2011 Jul 26;29(33):5558-66. doi: 10.1016/j.vaccine.2011.01.064. Epub 2011 Feb 5.

  PMID: 21300092 BACKGROUND

• Natz E, Lisziewicz J. Rational Design of Formulated DNA Vaccines: The DermaVir Approach. In J. Thalhamer, R. Weiss & S. Scheiblhofer (Eds.), Gene Vaccines. In press.

  RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

LC-002; Vaccination

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)

Immunotherapy, Active; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health

Limitations and Caveats

This is a Phase I/II small sample study that was not powered for the secondary efficacy endpoints.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Benigno Rodriguez, MD

  Division of Infectious Diseases ACTU, University Hospital of Cleveland, Cleveland, OH, USA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2005
• First Posted: December 26, 2005
• Study Start: January 1, 2006
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: November 4, 2021
• Results First Posted: October 13, 2011

Record last verified: 2017-12

Locations

US (5)