To evaluate the safety and tolerability, the antiviral activity, and plasma pharmacokinetics (PK) of zotatifin administered intravenously (IV) to adults with mild or moderate COVID-19.
This randomized, double-blind, placebo-controlled, dose-escalating study will evaluate the safety and efficacy of zotatifin administered IV to adults with mild or moderate COVID 19. Patients will be randomized to receive zotatifin or placebo in 3 cohorts of 12 patients each. Cohorts will be sequentially enrolled at progressively higher zotatifin dose levels. Study drug will not be administered to patients who are hospitalized. The second dose of study drug will not be administered should a patient progress from mild or moderate COVID-19 to severe COVID-19 prior to or on Day 8. Patients will assess and record their symptoms daily through Day 22 and at follow up (30 days after last infusion) (or at the early termination visit \[if conducted\]) in a paper patient diary using the WHO 9-point ordinal scale for clinical improvement. Other safety and efficacy measures will be assessed according to the Schedule of Procedures on Days 1, 4, 8, 10, 15 (end of treatment visit), and 22, and at follow up (30 days after last infusion). On non-dosing days, study visits will be conducted as home health visits, except for the follow-up visit, which will be conducted as a telephone visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
Zotatifin is a potent and sequence-selective inhibitor of eukaryotic translation initiation factor (eIF) 4A1-mediated translation that imparts its regulation through a reversible enhancement of eIF4A1 binding to RNAs (ribonucleic acids) with specific polypurine motifs within the 5'-untranslated region (UTR).
5% dextrose injection, USP
Pinnacle Research Group
Anniston, Alabama, United States
Cullman Clinical Trials
Cullman, Alabama, United States
Tampa General Hospital
Tampa, Florida, United States
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland, United States
Safety as assessed by the incidence of Treatment Emergent Adverse Events and Serious Adverse Events
Incidence of Treatment Emergent Adverse Events and Serious Adverse Events
Time frame: 52 days
Safety as assessed by the incidence of adverse events of special interest:
Adverse Events of Special Interest to be assessed: * Incidence of hospitalizations * incidence of cytokine release syndrome * hemophagocytic lymphohistiocytosis * acute respiratory distress syndrome * need for oxygen supplementation
Time frame: 52 days
Tolerability as assessed by changes in vital signs from baseline (Day 1)
Changes as assessed by respiration rate
Time frame: 22 days
Tolerability as assessed by changes in vital signs from baseline (Day 1)
Changes as assessed by heart rate
Time frame: 22 days
Tolerability as assessed by changes in vital signs from baseline (Day 1)
Changes as assessed by oxygen saturation
Time frame: 22 days
Tolerability as assessed by changes in vital signs from baseline (Day 1)
Changes as assessed by temperature
Time frame: 22 days
Tolerability as assessed by changes in vital signs from baseline (Day 1)
Changes as assessed by blood pressure
Time frame: 22 days
Tolerability as assessed by changes in clinical symptoms from baseline (Day 1)
Changes as assessed by physical exam
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Time frame: 22 days
Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)
Changes as assessed by serum chemistry
Time frame: 22 days
Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)
Changes as assessed by hematology
Time frame: 22 days
Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)
Changes as assessed by coagulation
Time frame: 22 days
Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)
Changes as assessed by urinalysis
Time frame: 22 days
Time to viral load undetectability;
Defined as the time to the first of 2 consecutive negative SARS-CoV-2 measurements assessed from swab specimen
Time frame: 22 days
Proportion of patients with SARS-CoV-2 viral load below the level of detectability;
Assessed by swab specimen
Time frame: 22 days
Mean change in SARS-CoV-2 viral load;
Assessed by swab specimen
Time frame: 22 days
The time to clinical resolution;
Defined as resolution of symptoms on the WHO 9-point ordinal scale for clinical improvement.
Time frame: 52 days
Zotatifin plasma concentrations
Concentrations at end of infusion, end of dosing interval, and on defined timepoint periods.
Time frame: 15 days