Intravenous Zotatifin in Adults With Mild or Moderate COVID-19

NCT04632381 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: eFT226-0003
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Corona Virus Infection

Keywords

COVID-19

Outcome Measures

Primary Outcomes (12)

• 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

  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

  52 days

• Tolerability as assessed by changes in vital signs from baseline (Day 1)

  Changes as assessed by respiration rate

  22 days

• Tolerability as assessed by changes in vital signs from baseline (Day 1)

  Changes as assessed by heart rate

  22 days

• Tolerability as assessed by changes in vital signs from baseline (Day 1)

  Changes as assessed by oxygen saturation

  22 days

• Tolerability as assessed by changes in vital signs from baseline (Day 1)

  Changes as assessed by temperature

  22 days

• Tolerability as assessed by changes in vital signs from baseline (Day 1)

  Changes as assessed by blood pressure

  22 days

• Tolerability as assessed by changes in clinical symptoms from baseline (Day 1)

  Changes as assessed by physical exam

  22 days

• Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

  Changes as assessed by serum chemistry

  22 days

• Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

  Changes as assessed by hematology

  22 days

• Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

  Changes as assessed by coagulation

  22 days

• Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

  Changes as assessed by urinalysis

  22 days

Secondary Outcomes (5)

• Time to viral load undetectability;

  22 days

• Proportion of patients with SARS-CoV-2 viral load below the level of detectability;

  22 days

• Mean change in SARS-CoV-2 viral load;

  22 days

• The time to clinical resolution;

  52 days

• Zotatifin plasma concentrations

  15 days

Other Outcomes (7)

• Time to viral load undetectability

  22 days

• Proportion of patients below the limit of detection

  22 days

• Mean change in viral load in saliva and nasal samples

  22 days

Study Arms (4)

Active Arm, Zota Cohort 1

ACTIVE COMPARATOR

0.01 mg/kg zotatifin

Drug: Zotatifin

Active Arm, Zota Cohort 2

ACTIVE COMPARATOR

0.02 mg/kg zotatifin

Drug: Zotatifin

Active Arm, Zota Cohort 3

ACTIVE COMPARATOR

0.035 mg/kg zotatifin

Drug: Zotatifin

Placebo

PLACEBO COMPARATOR

5% dextrose injection, USP

Drug: Placebo

Interventions

Zotatifin DRUG

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).

Also known as: Zota

Active Arm, Zota Cohort 1; Active Arm, Zota Cohort 2; Active Arm, Zota Cohort 3

Placebo DRUG

5% dextrose injection, USP

Also known as: PBO

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Has provided informed consent and any authorizations required by local law;
• Is a male or female patient ≥18 and \<65 years of age;
• Has a laboratory-documented positive test for SARS CoV 2 infection as determined by local laboratory using a standard, Food and Drug Administration (FDA)-approved viral RNA or viral antigen assay from any oral or respiratory sample collected within 48 hours of randomization;
• Has at least 2 symptoms associated with COVID-19 (fever or chills, cough, shortness of breath or difficulty breathing on exertion, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea) starting no more than 5 days prior to randomization and has mild or moderate disease at screening and at time of randomization, defined as the following:
• Mild COVID-19
• Positive testing by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent test;
• Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea; and
• No clinical signs indicative of moderate, severe, or critical severity;
• Moderate COVID-19
• Positive testing by standard RT-PCR assay or equivalent testing;
• Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion;
• Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥20 breaths per minute, saturation of oxygen (SpO2) \>93% on room air at sea level, heart rate ≥90 beats per minute; and
• No clinical signs indicative of severe or critical severity;
• Has adequate hepatic function during screening, defined as the following:
• Serum alanine aminotransferase ≤3 × upper limit of normal (ULN);

You may not qualify if:

• Is hospitalized for COVID-19;
• Has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure;
• Has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; ≥Grade 3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg); or history of congenital prolonged QT syndrome;
• Has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; Note: Intermittent use of a β2-agonist inhaler is allowed.
• Has evidence of an ongoing or systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) other than SARS-CoV-2 infection, recurrent or repeat SARS CoV 2 infection, or history of incompletely treated tuberculosis (TB) and/or suspected or known extrapulmonary TB; Note: Patients with localized fungal infections of the skin or nails are eligible. Patients may be receiving topical antifungals. Systemic administration of azole antifungals is prohibited (see Section 5.6).
• Has significant infiltrates (involving \>50% of lung parenchyma) on an optional standard of care chest X-ray or other lung imaging exam within 1 week of screening;
• Has known significant electrocardiogram abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (AV) block type II, third-degree AV block, ≥Grade 2 bradycardia, or QTcF \>450 msec for men or \>470 msec for women;
• Has type 1 diabetes mellitus or type 2 diabetes mellitus;
• Has a body mass index (BMI) \>30 kg/m2;
• Has received a live vaccine within 30 days prior to randomization;
• Has had major surgery within 4 weeks (inclusive) prior to randomization;
• Has had prior solid organ or bone marrow progenitor cell transplantation;
• Has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type);
• Has had prior high-dose chemotherapy requiring stem cell rescue;
• Has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system;

Sponsors & Collaborators

• Effector Therapeutics: lead
• Medpace, Inc.: collaborator

Study Sites (4)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Cullman Clinical Trials

Cullman, Alabama, 35055, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

National Institute of Allergy and Infectious Diseases

Bethesda, Maryland, 20814, United States

Location

Related Links

• Link to the study website; Propel Covid-19 Clinical Trial

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Douglas Warner, MD

  EFFECTOR Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be randomized 3:1 to receive zotatifin or placebo in 3 cohorts of 12 patients each. Cohorts will be sequentially enrolled at progressively higher zotatifin dose levels: 0.01, 0.02, or 0.035 mg/kg.

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 17, 2020
• Study Start: July 1, 2021
• Primary Completion: January 12, 2023
• Study Completion: September 22, 2023
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)