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.
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.
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
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
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
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 a COVID-19 vaccine and who have had their
last dose of COVID-19 vaccination at least 30 days prior to study entry. Healthy
individuals vaccinated with a COVID-19 booster shot are eligible for enrollment. The
vaccination dates of the doses, and specific vaccine received will be recorded.
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.
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
Health Research Innovation Centre
Calgary, Alberta, Canada
Andres M Salazar, MD, Study Director
Sponsor GmbH