A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19)

Phase 3TerminatedNCT04439071

PTC Therapeutics189 enrolled

Overview

This is a randomized, double-blind, placebo-controlled, multicenter, 28-day study of adult participants hospitalized with COVID-19, with a safety follow-up telephone call at Day 60.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

189

Conditions

Pneumonia COVID-19 Coronavirus

Interventions

PTC299DRUG

Oral tablets

SOCOTHER

As defined per local written policies or guidelines.

PlaceboDRUG

Oral tablets

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed and dated informed consent document(s). * Agrees to the collection of nasopharyngeal swabs and venous blood and all other protocol-specified procedures. * Male or non-pregnant female adult ≥18 years of age at time of enrollment. * Hospitalized and has laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). * Symptom onset was ≤10 days prior to screening. * Has oxygen saturation SpO2 \<94% on room air. * Has at least one of a respiratory rate \>24 breaths/minute or cough. * Lung involvement as confirmed by radiographic infiltrates observed on imaging (chest X-ray, computed tomography (CT) scan, or an equivalent test). * Women of childbearing potential (as defined in \[CTFG 2014\]) must have a negative pregnancy test at screening and agree to abstinence or the use at least one of the following highly effective forms of contraception (with a failure rate of \<1% per year when used consistently and correctly). Contraception or abstinence must be continued for the duration of the study following discharge from the hospital, and for up to 50 days after the last dose of study drug: i) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, and transdermal ii) progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, and implantable iii) intrauterine device iv) intrauterine hormone-releasing system v) vasectomized partner with confirmed azoospermia All females will be considered of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group without other known or suspected cause) or have been sterilized surgically (for example, bilateral tubal ligation, hysterectomy, bilateral oophorectomy). * Men sexually active with women of childbearing potential who have not had a vasectomy must agree to use a barrier method of birth control during the study following discharge from the hospital and for up to 50 days after the last dose of study drug. Exclusion Criteria: * Requires mechanical ventilation. * Current participation in any other interventional study. * Alanine transaminase/aspartate transaminase levels ≥3 times the upper limit of normal (×ULN) or total bilirubin (Tbili) ≥2×ULN. * Lymphocyte count \<500 lymphocytes/microliter (μL) or hemoglobin \<11 grams/deciliter (g/dL). * Stage 4 severe chronic kidney disease or requiring dialysis (that is, estimated glomerular filtration rate \<30). * Any other condition, that in the opinion of the Investigator, may be cause to exclude the participant from the study. * Use of steroids (except dexamethasone), sensitive CYP2D6 substrates, CYP2C inducers, IL-6 neutralizing antibodies, IL-6 receptor inhibitors, or any investigational therapy. * Pregnancy or breast feeding. * Anticipated transfer to another hospital which is not a study site within 72 hours. * Known allergy to PTC299 or excipients.

Locations (41)

Outcomes

Primary Outcomes

Time From Randomization to Respiratory Improvement

Respiratory improvement was defined as sustained peripheral oxygen saturation (SpO2) ≥94% on room air. Median time to respiratory improvement was estimated via the Kaplan-Meier product limit method.

Time frame: up to Day 28

Secondary Outcomes

Number of Participants Requiring Invasive Ventilation

Number of participants requiring invasive ventilation at any time during the study were reported.

Time frame: up to Day 28

Number of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants Who Did Not Require Supplemental Oxygen at Baseline

Number of participants requiring supplemental oxygen or non-invasive ventilation at any point during the study in participants who did not require supplemental oxygen at baseline were reported.

Time frame: up to Day 28

Time From Randomization to Defervescence in Participants Presenting With Fever at Enrollment (Temperature of ≥37.6℃ Axilla, ≥38.0℃ Oral, or ≥38.6°C Tympanic or Rectal)

Defervescence was defined as body temperature of \<37.6° C axilla, \<38.0° C oral, or \<38.6° C tympanic or rectal without taking any antipyretic treatment and sustained until discharge or Day 28. Median time to defervescence was estimated via the Kaplan-Meier method.

Time frame: up to Day 28

Time From Randomization to Respiratory Rate ≤ 24 Breaths Per Minute on Room Air

Median time to respiratory rate in participants who had abnormal respiratory rate at baseline was estimated via the Kaplan-Meier method.

Time frame: up to Day 28

Time From Randomization to Cough Reported as Mild or Absent

Data from ClinicalTrials.gov

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University of California, Irvine

Orange, California, United States

Augusta University

Augusta, Georgia, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, United States

University Hospitals Cleveland

Cleveland, Ohio, United States

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, United States

Westmead Hospital

Westmead, New South Wales, Australia

Sunshine Hospital

St Albans, VC, Australia

Monash Medical Centre

Clayton, Victoria, Australia

St. Pierre University Hospital

Brussels, Belgium

...and 31 more locations

Cough was rated on a scale of severe, moderate, mild, absent, in those with cough at enrollment rated severe or moderate. Median time to cough reported as mild or absent was estimated via the Kaplan-Meier method.

Time frame: up to Day 28

Time From Randomization to Dyspnea Reported as Mild or Absent

Dyspnea was rated on a scale of severe, moderate, mild, absent, in those with dyspnea at enrollment rated as severe or moderate. Median time to dyspnea reported as mild or absent was estimated via the Kaplan-Meier method.

Time frame: up to Day 28

Change From Baseline in Cytokine Levels at Day 28

Cytokines included Granulocyte Colony Stimulating factor; Interleukin 10, 17, 2, 6, 7; Macrophage Inflammatory Protein 1 Alpha; Monocyte Chemotactic Protein 1; and Tumor Necrosis Factor.

Time frame: Baseline, Day 28

Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28

Time frame: Baseline, Day 28

Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28

Time frame: Baseline, Day 28

Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28

Time frame: Baseline, Day 28

Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28

Time frame: Baseline, Day 28

Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline

Number of participants who returned to normal range CBC were reported. CBC included red blood cell (RBC), hemoglobin (HGB), white blood cell (WBC), and Platelets.

Time frame: up to Day 28

Change From Baseline in Viral Load at Day 28: SARS-CoV-2 Immunoglobulin A (IgA) Antibody Ratio and SARS-CoV-2 Immunoglobulin G (IgG) Antibody Ratio

Time frame: Baseline, Day 28

Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance

Time frame: Baseline, Day 28

Change From Baseline in Viral Load at Day 28: SARS-CoV2 v2, SARS-CoV2 v2 Nasopharyngeal Swab (NPsw), and Severe Acute Resp Syndrome Coronavirus 2

Time frame: Baseline, Day 28

Duration of Hospitalization

Time frame: up to Day 28

Number of Mortalities at Day 28

Mortality was defined as a death event occurring at anytime before the specific date, after the first dose has been received.

Time frame: Day 28

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TEAEs were defined as any AEs that occurred on or after the first study treatment through 30 days after the last dose, or any AEs occurring before the first study treatment but worsening during the treatment through 30 days after the last dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Time frame: up to Day 60