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Nasal Poly-ICLC (Hiltonol®) in Healthy COVID-19 Vaccinated Adults

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ClinicalTrials.gov Identifier: NCT04672291
Recruitment Status : Not yet recruiting
First Posted : December 17, 2020
Last Update Posted : June 14, 2021
Sponsor:
Collaborator:
University of Calgary
Information provided by (Responsible Party):
Oncovir, Inc.

Brief Summary:
This is a randomized (4:1) Phase 1 b safety trial in adults who have completed their full COVID-19 vaccination schedule at least 30 days prior to study entry.

Condition or disease Intervention/treatment Phase
COVID - 19 Drug: Poly-ICLC (Hiltonol®) or Placebo Phase 1

Detailed Description:

An initial cohort of 13 participants will receive 2 cycles of drug or placebo per the schedule below under carefully monitored conditions, including examinations to observe and document administration site reaction following consecutive administration cycles of the drug. 10 participants will receive drug and 3 will receive placebo. The safety stopping rule is to implement an enrollment pause if 2 dose limiting toxicity (DLT, see section 5.1) out of the first six or 3 DLTs out of the first 10 participants receiving drug are observed in either cycle 1 or cycle 2. The independent DSMB will conduct a review of the safety data to determine the relatedness of the DLTs to the drug exposure and provide a recommendation to continue. Thus, if safety events are determined to be not (or unlikely) related to drug exposure the trial may resume. The independent DSMB will review safety and tolerance data before the study can continue.

If at most 2 DLTs out of the 10 participants receiving drug are observed, then a Phase Ib expansion cohort will open. The expansion cohort will receive 3 cycles of therapy. A total of 30 participants will be accrued and randomized 4:1 to receive drug (N=24) or placebo (N=6). There will be extensive assessment of toxicity and an early stopping rule to implement an enrollment pause and independent DSMB review of safety data to determine relatedness to drug exposure for recommendation of trial continuation, will be employed as above. Safety and tolerability will be the primary endpoint but secondary endpoints include changes in immunological parameters.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Intranasal Poly-ICLC (Hiltonol®) or Placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This study consists of 2 treatment groups. Study subjects will be assigned by chance to a treatment group. Group 1 receives the study drug; group 2 receives the placebo. Neither the study subject or the study team will know the group assignments. There will be a 4 out 5 chance of receiving the study drug and 1 out 5 chance of receiving the placebo.
Primary Purpose: Prevention
Official Title: A Phase I-Ib, Double-blinded, Randomized Repeated Dose Single Center, Safety and Immunogenicity Study of Nasal Poly-ICLC (Hiltonol®) in Healthy COVID-19 Vaccinated Adults
Estimated Study Start Date : June 15, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : January 16, 2024

Arm Intervention/treatment
Experimental: Safety Cohort
A randomized (4:1) initial safety cohort of 13 patients will receive 2 cycles of drug (N=10) or placebo (N=3)
Drug: Poly-ICLC (Hiltonol®) or Placebo
The safety cohort (Cohort A) consists of 13 patients who will be randomized to receive 2 cycles of the study drug (N10) or 2 placebo cycles (N3).
Other Name: Safety

Experimental: Expansion Cohort
A randomized (4:1) expansion cohort will receive 3 cycles of drug (N=24) or placebo (N=6). A total of 30 patients will be accrued.
Drug: Poly-ICLC (Hiltonol®) or Placebo
The expansion cohort will receive 3 cycles of therapy. A total of 30 patients will be accrued and randomized 4:1 to receive drug (N=24) or placebo (N=6).
Other Name: Expansion




Primary Outcome Measures :
  1. Safety and tolerability of nasally administered Poly-ICLC (Hiltonol®) in healthy adults. [ Time Frame: 91 days ]
    Safety will be measured and tabulated by the number (percent) of participants who experience DLTs (grade 3/4 adverse events) from the start of therapy through the end of the follow up period (day 91), according to DAIDS.


Secondary Outcome Measures :
  1. Assess the response of the body to the study drug (pharmacodynamics) [ Time Frame: 91 days ]
    Characterize the pharmacodynamics of the local and systemic innate immune response to repeated doses of intranasal Poly-ICLC (Hiltonol®) by investigating the effects on nasal mononuclear cells and systemic inflammatory markers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for Enrollment

  1. Phase I Cohort A: Subjects must be between 18 and 69 years of age. Phase 1b Cohort B: Subjects must be 18 years of age or older. In order to mitigate risk, no participants over age 70 will be recruited in Cohort A.
  2. Asymptomatic; defined by experiencing none of the symptoms identified in the Symptom Questionnaire (Appendix 1)

    1. fever
    2. cough
    3. dyspnea
    4. fatigue
    5. muscle or joint pain
    6. sore throat
    7. stuffy or runny nose
    8. nausea/vomiting
    9. headache
    10. confusion
    11. diarrhea
    12. loss of smell or taste
  3. Nasopharyngeal swab for COVID-19 at screening with negative diagnosis of SARS-CoV-2
  4. Willing and able to provide blood, nasopharyngeal swab, and nasal mononuclear samples
  5. Healthy individuals fully vaccinated with an mRNA COVID-19 vaccine (Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine (mRNA-173) and who have had their last dose of COVID-19 vaccination at least 30 days prior to study entry. The vaccination dates of the doses, and specific vaccine received will be recorded. Accrual will be limited to participants who have received one of the two available mRNA vaccines to reduce potential variability in the study and to minimize any yet unknown variables in the immunologic data.
  6. Able to provide informed consent
  7. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use adequate methods of contraception (described below) during the study treatment and through 90 days after the last dose of study medication. Female participants of childbearing potential are all those except participants who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal
  8. Acceptable Hematologic, renal and liver functions as follows:

1. Absolute neutrophil count > 1000/mcL 2. Platelets > 50,000/mcL 3. Hemoglobin >9 g/dL 4. Serum Creatinine ≤ 2.5 mg/dl 5. Liver Function:

  • Total bilirubin ≤1.5 mg/dl
  • AST ≤ 2.0 mg/dl (≤120 IU or 3x ULN)

Exclusion Criteria

  1. Individuals not yet fully vaccinated with a COVID-19 vaccine or fully vaccinated with a COVID-19 vaccine other than an mRNA COVID-19 vaccine.
  2. Receipt of any blood product in past 120 days
  3. Allergic rhinitis, chronic sinusitis, or other nasal inflammatory disease that requires daily intranasal or oral medication
  4. Chronic medical problems that require daily nasal administration of medication
  5. Prior nasal or sinus surgery including trans nasal approaches to brain
  6. Chronic pulmonary conditions including severe asthma, COPD, or chronic bronchitis
  7. Autoimmune hepatitis, decompensated liver disease, cardiac ischemia, congestive heart failure, cardiac arrhythmia, neutropenia, thrombocytopenia, severe renal insufficiency
  8. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect participant safety and/or compliance
  9. Symptoms consistent with COVID-19 infection (fevers, acute onset cough, shortness of breath) at time of screening
  10. Nucleic acid testing evidence of COVID-19 infection at time of screening
  11. Participants must not be pregnant or nursing due to the unknown potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
  12. Has a diagnosis of primary immunodeficiency
  13. Has uncontrolled hypertension that in the opinion of the principal investigator poses unacceptable risk.
  14. Has active autoimmune disease that has required systemic treatment in the past 1 year

    1. (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
    2. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable
  15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator
  16. Principle investigator believes that for one or multiple reasons the participant will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the participant
  17. Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps)
  18. Active, untreated tuberculosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04672291


Contacts
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Contact: Andres M Salazar, MD 207 505 7144 asalazar@oncovir.com
Contact: Richard Leigh, MBChB, PhD 403-220-2123 rleigh@ucalgary.ca

Locations
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Canada, Alberta
Health Research Innovation Centre
Calgary, Alberta, Canada, T2N 4Z6
Contact: Curtis Dumonceaux, BSc, CCRP    403-220-2123    cjdumonc@ucalgary.ca   
Contact: Linda Knox, RN, CRE    403-220-2123    lknox@ucalgary.ca   
Principal Investigator: Richard Leigh, MBChB, PhD         
Sponsors and Collaborators
Oncovir, Inc.
University of Calgary
Investigators
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Study Director: Andres M Salazar, MD Sponsor GmbH
Publications of Results:
Burrer S, Ma D, Hughes M, Kuhar D, Luckhaupt S, McDaniel C, et al. Characteristics of Health Care Personnel with COVID-19 - United States, February 12-April 9, 2020. CDC Morbidity and Mortality Report. 2020;69.
Christopher ME, Wong JP. Use of TLR3 receptor agaonists against respiratory viral infections. Anti-inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 2011;10:327-38.

Other Publications:
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Responsible Party: Oncovir, Inc.
ClinicalTrials.gov Identifier: NCT04672291    
Other Study ID Numbers: ONV2020-003
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: June 14, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Oncovir, Inc.:
SARS CoV-2
COVID
Prevention
Poly-ICLC
Viral Infection
Additional relevant MeSH terms:
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Poly I-C
Carboxymethylcellulose Sodium
Poly ICLC
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents