Clinical Trials

MainTitle

DCVax Plus Poly ICLC in Healthy Volunteers

This study has been completed
Sponsor
Rockefeller University


Information provided by (Responsible Party)
Rockefeller University
ClinicalTrials.gov Identifier
NCT01127464

First received: May 19, 2010
Last updated: May 7, 2014
Last Verified: May 2014
History of Changes
Purpose

Purpose

DCVax-001 is a recombinant protein vaccine designed to prevent and potentially treat human immunodeficiency virus (HIV) infection. The vaccine is composed of a fusion protein containing a human monoclonal antibody specific for the dendritic cell receptor, DEC-205 (CD205), and the HIV gag p24 protein. The vaccine is designed to target HIV antigens directly to endocytic pathways in dendritic cells (DCs) that allow for efficient processing and presentation of multiple HIV peptides on both MHC class I and II products, which will induce HIV-specific CD8+ and CD4+ T cells. This vaccine candidate must be combined with appropriate immunostimulants (adjuvants) to induce immunity to the antigen. In the proposed clinical trial we will use poly ICLC (Hiltonol) from Oncovir, Inc as the adjuvant.

Condition Intervention Phase
HIV-1 Infection
HIV Infection
Healthy Volunteers

Drug : DCVax-001
Drug : Poly-ICLC
Drug : Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A Randomized, Placebo-controlled, Dose-escalating, Double-blinded Phase I Study to Evaluate the Safety and Immunogenicity of Anti-DEC-205 Monoclonal Antibody (Mab) Targeted HIV Gag p24 Vaccine (DCVax-001) With Poly ICLC (Hiltonol) as Adjuvant in HIV-uninfected Healthy Volunteers

Further study details as provided by Rockefeller University:

Primary Outcome Measures

  • safety and tolerability [ Time Frame: 64 weeks ]
    The proportion of volunteers with moderate local reactogenicity events; Proportion of volunteers with moderate systemic reactogenicity events; Proportion of volunteers with other moderate adverse events; Proportion of volunteers with serious adverse events; Proportion of volunteers with severe and moderate local and systemic reactogenicity events and adverse events.
Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: 64 weeks ]
    The proportion of volunteers with HIV-1 specific T-cell responses as quantified by IFNγ-ELISpot; The proportion of volunteers with HIV-1 specific T-cell responses as quantified by multiparametric cytokine flow cytometry; The proportion of volunteers with binding antibody responses; All immune responses will be evaluated for proportion of responders and the mean responses will be compared.

Enrollment: 43
Study Start Date: May 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: .3 dose level of DCVax -001
.3 dose level of DCVax plus fixed dose of 1.6 ml Poly ICLC
Drug: DCVax-001

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Drug: Poly-ICLC

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Experimental: 1 mg dose level of DCVax -001
1 mg dose level of DCVax -001 plus 1.6 ml of poly ICLC
Drug: DCVax-001

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Drug: Poly-ICLC

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Experimental: 3 mg dose level of DCVax-001
3 mg dose level of DCVax-001 plus poly ICLC
Drug: DCVax-001

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Drug: Poly-ICLC

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Placebo Comparator: Placebo
sterile saline
Drug: Placebo

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Experimental: poly-ICLC alone
1.6 mg of poly-ICLC alone
Drug: Poly-ICLC

Comparison of 3 different doses of DCVax-001 administered with poly-ICLC, the administration of poly-ICLC alone, or a placebo control

Detailed Description:

This trial will investigate whether delivery of HIV antigens via immunization with anti-DEC-205 p24 monoclonal antibody plus poly ICLC, as an adjuvant, is safe and induces either cellular or humoral immunogenicity in healthy volunteers. We propose to assess the quality of immunity elicited by DEC targeted vaccines in humans. Immunogenicity after HIV antigen delivery directly to dendritic cells could provide the proof-of-concept that dendritic cell targeted protein vaccines may serve as a stand-alone vaccine strategy or in combination with other vaccine modalities against HIV or other diseases.
The main hypothesis of this study is to assess the delivery of HIV antigens via immunization with anti-DEC-205 p24 monoclonal antibody (DCVax-001) plus poly ICLC (Hiltonol) is safe and induces either cellular or humoral immunogenicity in HIV-uninfected, healthy volunteers.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 60 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

  1. Healthy adult males and females, as assessed by a medical history, physical exam, and laboratory tests
  2. Age of at least 18 years of age on the day of screening and no greater than 60 years at time of vaccination
  3. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study (screening plus 15 months)
  4. In the opinion of the principal investigator or designee, has understood the information provided. (Written informed consent needs to be given before any study-related procedures are performed)
  5. Amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
  6. Assessed by the clinic staff as being at "low risk" for HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment defined as follows:
    • Sexually abstinent OR
    • Had two or fewer mutually monogamous relationships with partners believed to be HIV-uninfected and who did not use illicit drugs (illicit drug use or abuse that includes any injection drugs, methamphetamines (crystal meth), heroin, cocaine, including crack cocaine or chronic marijuana abuse) OR
    • Had two or fewer partners believed to be HIV-uninfected and who did not use illicit drugs (as defined above) and with whom he/she regularly used condoms for vaginal and anal intercourse;
  7. If sexually active female, using an effective method of contraception (combined oral contraceptive pill; injectable contraceptive; diaphragm; Intra Uterine Device (IUD); condoms; anatomical sterility in self or partner) throughout the study period. All female volunteers must be willing to undergo urine pregnancy tests at time points as indicated
  8. If sexually active male, willing to use an effective method of contraception (such as condoms, anatomical sterility) from screening until 4 weeks after last vaccination (same as above) and will be advised not to get his partner(s) pregnant

  • Exclusion Criteria:
  • Confirmed HIV-1 or HIV-2 infection
  • Any clinically significant abnormality on history or examination including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids immunosuppressive anticancer, or other medications considered significant by the trial physician within the last 6 months
  • Any clinically significant acute or chronic medical condition requiring care of a physician (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that in the opinion of the investigator would preclude participation
  • Any laboratory value outside of reference range, with the exception of any non-clinically significant Grade I elevations of liver function tests (AST, ALT, direct/total bilirubin), electrolytes, CO2, CBC, urinalysis as determined by the Principal Investigator or his designee as well as creatinine if the estimated glomerular filtration rate is > 60 mL/min/1.73 m2
  • Within the 12 months prior to enrollment, the volunteer has had excessive daily alcohol use or frequent binge drinking or chronic marijuana abuse or any other use of illicit drugs
  • Within the 12 months prior to enrollment, the volunteer has a history of newly-acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies)
  • If female, pregnant, planning a pregnancy during the trial period, or lactating
  • Receipt of a live attenuated vaccine within 30 days or other vaccine within 14 days prior to DEC-205 vaccination
  • Receipt of another experimental HIV vaccine at any time
  • Receipt of blood transfusion or blood products 6 months prior to vaccination
  • Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study
  • History of severe local or systemic reactogenicity to vaccination or history of severe allergic reactions
  • Major psychiatric illness
  • In the opinion of the investigator, unlikely to comply with protocol

    contacts and locations

    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: NCT01127464

    Locations

    United States, New York
    Rockefeller University
    New York, New York, United States, 10065

    Sponsors and Collaborators

    Rockefeller University

    Investigators

    Principal Investigator: Sarah Schlesinger, MD The Rockefeller University
    More Information

    More Information

    Additional Information:

    Rockefeller Univesity research program information page

    Responsible Party: Rockefeller University  
    ClinicalTrials.gov Identifier: NCT01127464   History of Changes  
    Other Study ID Numbers: SSC-0710  
    Study First Received: May 19, 2010  
    Last Updated: May 7, 2014  

    Keywords provided by Rockefeller University:

    HIV-1
    HIV preventative vaccine
    Healthy Volunteers

    Additional relevant MeSH terms:
    Infection
    Communicable Diseases
    HIV Infections
    Poly ICLC
    Poly I-C
    Carboxymethylcellulose Sodium

    ClinicalTrials.gov processed this data on December 15, 2017
    This information is provided by ClinicalTrials.gov.