DCVax Plus Poly ICLC in Healthy Volunteers

Sponsor

Rockefeller University (Other)

Overall Status

Completed

CT.gov ID

NCT01127464

Collaborator

(none)

Enrollment

Location

Arms

30.1

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
HIV-1 Infection HIV Infection Healthy Volunteers	Drug: DCVax-001 Drug: Poly-ICLC Drug: Placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

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

Study Start Date :

May 1, 2010

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

safety and tolerability [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy adult males and females, as assessed by a medical history, physical exam, and laboratory tests
Age of at least 18 years of age on the day of screening and no greater than 60 years at time of vaccination
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)
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)
Amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
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;

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
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