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

Study Overview
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Brief Summary
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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.

Official Title
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Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)

Conditions
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Pneumonia, COVID-19, Coronavirus

Intervention / Treatment
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* Drug: PTC299
* Other: SOC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTC299 + Standard of Care (SOC)<br>Participants will receive PTC299 at 200 milligrams (mg), administered orally, twice daily (BID) on Days 1 to 7, then at 50 mg administered orally, once daily (QD) on Days 8 to 14. SOC will also be administered according to local, written policies or guidelines. | Drug: PTC299<br>* Oral tablets<br>* Other names: Emvododstat;Other: SOC<br>* As defined per local written policies or guidelines.<br>|
| Placebo Comparator: Placebo + SOC<br>Participants will receive PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14. SOC will also be administered according to local, written policies or guidelines. | Other: SOC<br>* As defined per local written policies or guidelines.<br>Drug: Placebo<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Requiring Invasive Ventilation | Number of participants requiring invasive ventilation at any time during the study were reported. | 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. | 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. | 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. | up to Day 28 | 
| Time From Randomization to Cough Reported as Mild or Absent | 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. | 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. | 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. | Baseline, Day 28 | 
| Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28 |  | Baseline, Day 28 | 
| Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28 |  | Baseline, Day 28 | 
| Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28 |  | Baseline, Day 28 | 
| Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28 |  | 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. | 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 |  | Baseline, Day 28 | 
| Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance |  | 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 |  | Baseline, Day 28 | 
| Duration of Hospitalization |  | 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. | 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. | up to Day 60 |