Polyinosinic-Polycytidylic Acid-poly-L-lysine Carboxymethylcellulose (Poly-ICLC) in Healthy Volunteers
This study has been completed.
Information provided by (Responsible Party):
First received: February 14, 2011
Last updated: August 10, 2012
Last verified: August 2012
Vaccines induce protective immunity against numerous infectious diseases. However, current vaccines have limited efficacy against challenging infections like tuberculosis, malaria, and HIV. Protein vaccines are safe but, typically they induce weak T cell immunity when administered alone. Therefore, special attention is being given to adjuvants, which are enhancers of immunity, that cab mature antigen presenting immunostimulatory dendritic cells. Our goal is to study in humans the mechanism whereby a synthetic adjuvant, poly ICLC, which acts on defined pattern recognition receptors, enhances T an B cell immunity. In preclinical studies, our lab has found in mice that poly IC and its analog poly ICLC are superior adjuvants for T cell mediated immunity relative to other agonists for PRR. Poly ICLC has been extensively studied in humans with a favorable safety profile. In a recently completed Phase I study, poly ICLC was found to be safe and well tolerated when administered as a single dose of 1.6 mg subcutaneously and intranasally to healthy volunteers. In additional, preliminary data shows marked upregulation of gene expression in whole PBMSc following s.c. injection of poly ICLC as well as activation of various blood cell type, including dendritic cells and monocytes. In this study the investigators propose to extend the evaluation of innate immune responses following s.d. injection of poly ICLC to healthy volunteers. The investigators propose to characterize poly ICLC effects on specific blood cell types, focusing on three different subsets of DC's, by analyzing gene transcriptional changes at baseline and at one day following its administration. In order to study the early local effects of poly ICLC, which are important for the recruitment and activation of antigen presenting cells, the investigators also propose to perform skin biopsies at a skin site contralateral to the injection site and at the injection site after poly ICLC injections.
Drug: Poly ICLC
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
||An Open Label Study to Evaluate Innate Immune Responses Induced by a Pattern Recognition Receptor Agonist, Poly-ICLC (Hiltonol), in Healthy Volunteers
Primary Outcome Measures:
- To evaluate the innate immune responses to poly ICLC in different blood cell types, including three subsets of dendritic cells after subcutaneous administration to healthy volunteers. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
The variables to be assessed include:
- Transcriptional arrays in whole PBMCs and in 8 subsets of blood leukocytes (naïve and memory T, NK, B, monocytes and three different subsets of dendritic cells (BDCA1+, BDCA3+ and BDCA2+ plasmacytoid DCs) following s.c. administration of poly ICLC.
- Flow cytometric analysis of activation markers in different subsets of blood leukocytes.
- Measurement of cytokines in the serum and/or plasma following s.c. administration of poly ICLC.
Secondary Outcome Measures:
- To evaluate the reproducibility of innate immune responses in whole PBMCs after a second dose of poly ICLC, in volunteers who participated in protocol MAC-682 and now return to participate in this proposed study. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The following variable will be assessed:
- Transcriptional analysis of whole PBMC samples at different timepoints following the first dose and the second dose of poly ICLC in volunteers who participated in protocol MAC-682 and are now returning to participate in this proposed study.
- To evaluate innate immune responses to poly ICLC at the injection site. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
The following will be assessed:
- Routine histology and immunohistochemistry to evaluate cellular infiltrates following subcutaneous injection of poly ICLC.
- Transcriptional analysis of skin samples from study drug injection site and from a non-lesional site of skin.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||September 2011 (Final data collection date for primary outcome measure)
Experimental: Poly ICLC
One 1.6 mg subcutaneous injection of the adjuvant, poly ICLC, in the upper arm.
Drug: Poly ICLC
One 1.6 mg subcutaneous injection of the study drug, poly ICLC in the upper arm.
|Ages Eligible for Study:
||18 Years to 60 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Age of at least 18 years on the day of screening and no greater than 60 years at the time of drug/placebo administration
- Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study (screening plus 2 weeks)
- 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
- Willing to undergo HIV testing and counseling, and receive HIV test results
- If a sexually active male, willing to use an effective measure of contraception(condoms, anatomical sterility) throughout the study period and will be advised not to get his partner pregnant for 6 weeks after study drug administration
Females of child-bearing potential must agree to use one of the following methods of contraception for 2 weeks prior to date of screening evaluation through 6 weeks after study drug administration:
Be surgically sterile Be abstinent (or willing to be) Use oral contraceptives, or other form of hormonal birth control including hormonal vaginal rings or transdermal patches Use an intra-uterine device (IUD) Use (by ensuring her male partner(s)uses)barrier contraception (condom) with spermicide Any other equivalent (as judged by the investigative team) methods of contraception
- Healthy adult males and females, as assessed by a medical history, physical exam, and laboratory tests
- Allergy to lidocaine
- 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 conditions 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 (Na, K, Cl, CO2), Glucose, CBC, 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
- Confirmed diagnosis of hepatitis B (surface antigen, HbsAg); hepatitis C (HCV antibodies) or active syphilis
- 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 of poly ICLC administration
- Receipt of blood transfusion or blood products 6 months prior to drug administration
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01299662
|The Rockefeller University
|New York, New York, United States, 10065 |
||Marina Caskey, MD
||The Rockefeller University
History of Changes
|Other Study ID Numbers:
|Study First Received:
||February 14, 2011
||August 10, 2012
||United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 03, 2016
Physiological Effects of Drugs