A Study to Evaluate Efficacy and Safety of PTC299 (Emvodo... | NCT04439071

ID	Type	Description	Link
2020-001872-13	EudraCT Number

Label	Type	Description	Intervention Names
PTC299 + Standard of Care (SOC)	Experimental	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 Other: SOC
Placebo + SOC	Placebo Comparator	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 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
PTC299	Drug	Oral tablets	PTC299 + Standard of Care (SOC)	Emvododstat

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

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

Measure	Description	Time Frame
Time From Randomization to Respiratory Improvement Where Symptom Onset Occurred ≤5 Days	Respiratory improvement was defined as SpO2 ≥94% on room air. Median time to respiratory improvement was estimated via the Kaplan-Meier product limit method.	up to Day 28

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Quintus Ngumah, OD, PhD	PTC Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of California, Irvine		Orange	California	92868	United States
Augusta University

Label	URL
FINAL REDACTED PROTOCOL	View source

ID	Title	Description
FG000	PTC299	Participants received 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.
FG001	Placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 2, 2021	May 30, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Intent-to-treat (ITT) population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG00073 OG00176

Title

Denominators

Categories

Title	Measurements
	OG00010.0(6.0 to 15.0) OG00110.0(8.0 to 13.0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Time to respiratory improvement was compared between treatment groups using stratified log-rank test.	Log Rank		0.949														Other

Secondary

Number of Participants Requiring Invasive Ventilation

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

ITT population included all randomized participants.

Posted

Count of Participants

Participants

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Count of Participants

Participants

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants

Secondary

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.

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

nanograms (ng)/liter (L)

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

mg/L

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

micrograms (µg)/L D-dimer units (DDU)

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

picomoles (pmol)/L

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Posted

Mean

Standard Deviation

µg/L

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

Posted

Count of Participants

Participants

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

Posted

Mean

Standard Deviation

ratio

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

absorbance (Abs)

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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

Posted

Mean

Standard Deviation

copies/mL

Baseline, Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

Duration of Hospitalization

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

Safety population included all randomized participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Secondary

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.

Safety population included all randomized participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

up to Day 60

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Other Pre-specified

Time From Randomization to Respiratory Improvement Where Symptom Onset Occurred ≤5 Days

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

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

days

up to Day 28

ID	Title	Description
OG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
OG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00010 affected92 at risk EG0018 affected95 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0003 affected92 at risk EG0013 affected95 at risk
Organising pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0013 affected95 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Septic shock	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0004 affected92 at risk EG0011 affected95 at risk
Sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 affected92 at risk EG0011 affected95 at risk
Pneumonia acinetobacter	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0011 affected95 at risk
Bacteraemia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Dengue fever	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0004 affected92 at risk EG0012 affected95 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Cardiogenic shock	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Right ventricular dysfunction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Cardiac arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0011 affected95 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0012 affected95 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Haemoglobin decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Blood bilirubin increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0012 affected95 at risk
Disease progression	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0012 affected95 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected95 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected95 at risk

ID	Term
D011014	Pneumonia
D000086382	COVID-19
D018352	Coronavirus Infections

ID	Term
D012141	Respiratory Tract Infections
D007239	Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D011024	Pneumonia, Viral
D014777	Virus Diseases
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections

ID	Title	Description
BG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.
BG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PTC299	Participants received PTC299 at 200 mg, administered orally, BID on Days 1 to 7, then at 50 mg administered orally, QD on Days 8 to 14.	9	92	21	92	50	92
EG001	Placebo	Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14.	4	95	24	95	63	95