Coronavirus, COVID-19, Pneumonia
Conditions
Brief summary
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.
Interventions
DRUGPTC299
Oral tablets
OTHERSOC
As defined per local written policies or guidelines.
DRUGPlacebo
Oral tablets
Sponsors
PTC Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to Respiratory Improvement | up to Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requiring Invasive Ventilation | up to Day 28 | Number of participants requiring invasive ventilation at any time during the study were reported. |
| Number of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants Who Did Not Require Supplemental Oxygen at Baseline | up to Day 28 | 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 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) | up to Day 28 | 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 From Randomization to Respiratory Rate ≤ 24 Breaths Per Minute on Room Air | up to Day 28 | Median time to respiratory rate in participants who had abnormal respiratory rate at baseline was estimated via the Kaplan-Meier method. |
| Time From Randomization to Cough Reported as Mild or Absent | up to Day 28 | 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 From Randomization to Dyspnea Reported as Mild or Absent | up to Day 28 | 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. |
| Change From Baseline in Cytokine Levels at Day 28 | Baseline, 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. |
| 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 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 | up to Day 28 | 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. |
| 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 | Day 28 | Mortality was defined as a death event occurring at anytime before the specific date, after the first dose has been received. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | up to Day 60 | 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. |
| Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28 | Baseline, Day 28 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to Respiratory Improvement Where Symptom Onset Occurred ≤5 Days | up to Day 28 | Respiratory improvement was defined as SpO2 ≥94% on room air. Median time to respiratory improvement was estimated via the Kaplan-Meier product limit method. |
Countries
Australia, Belgium, Brazil, Colombia, France, Mexico, Poland, Portugal, South Africa, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 92 |
| Placebo Participants received PTC299-matching placebo administered orally, BID on Days 1 to 7, then administered orally, QD on Days 8 to 14. | 95 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 4 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Other than specified | 3 | 3 |
| Overall Study | Randomized but not treated | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | PTC299 |
|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 12.48 | 52.3 years STANDARD_DEVIATION 12.44 | 52.0 years STANDARD_DEVIATION 12.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 117 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 60 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 19 Participants | 31 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 69 Participants | 138 Participants | 69 Participants |
| Sex: Female, Male Female | 27 Participants | 52 Participants | 25 Participants |
| Sex: Female, Male Male | 68 Participants | 135 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 92 | 4 / 95 |
| other Total, other adverse events | 50 / 92 | 63 / 95 |
| serious Total, serious adverse events | 21 / 92 | 24 / 95 |
Outcome results
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.
Time frame: up to Day 28
Population: Intent-to-treat (ITT) population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTC299 | Time From Randomization to Respiratory Improvement | 10.0 days |
| Placebo | Time From Randomization to Respiratory Improvement | 10.0 days |
Comparison: Time to respiratory improvement was compared between treatment groups using stratified log-rank test.p-value: 0.949Log Rank
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.
Time frame: Baseline, Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 17 | 0.018 nanograms (ng)/liter (L) | Standard Deviation 0.1447 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Tumor Necrosis Factor | -0.015 nanograms (ng)/liter (L) | Standard Deviation 0.1509 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 2 | 0.021 nanograms (ng)/liter (L) | Standard Deviation 0.0868 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Granulocyte Colony Stimulating Factor | -0.423 nanograms (ng)/liter (L) | Standard Deviation 0.4431 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 6 | -0.375 nanograms (ng)/liter (L) | Standard Deviation 0.5274 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Macrophage Inflammatory Protein 1 Alpha | 0.072 nanograms (ng)/liter (L) | Standard Deviation 0.2459 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 10 | -0.367 nanograms (ng)/liter (L) | Standard Deviation 0.4655 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Monocyte Chemotactic Protein 1 | -0.011 nanograms (ng)/liter (L) | Standard Deviation 0.4077 |
| PTC299 | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 7 | -0.025 nanograms (ng)/liter (L) | Standard Deviation 0.1233 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Monocyte Chemotactic Protein 1 | 0.018 nanograms (ng)/liter (L) | Standard Deviation 0.3804 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 7 | -0.035 nanograms (ng)/liter (L) | Standard Deviation 0.1556 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Tumor Necrosis Factor | -0.027 nanograms (ng)/liter (L) | Standard Deviation 0.1666 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Granulocyte Colony Stimulating Factor | -0.467 nanograms (ng)/liter (L) | Standard Deviation 0.475 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 10 | -0.491 nanograms (ng)/liter (L) | Standard Deviation 0.4003 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 17 | 0.002 nanograms (ng)/liter (L) | Standard Deviation 0.1425 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 2 | 0.022 nanograms (ng)/liter (L) | Standard Deviation 0.1448 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Macrophage Inflammatory Protein 1 Alpha | 0.044 nanograms (ng)/liter (L) | Standard Deviation 0.1888 |
| Placebo | Change From Baseline in Cytokine Levels at Day 28 | Interleukin 6 | -0.442 nanograms (ng)/liter (L) | Standard Deviation 0.5062 |
Secondary
Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28
Time frame: Baseline, Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTC299 | Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28 | -1.027 mg/L | Standard Deviation 0.5966 |
| Placebo | Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28 | -1.111 mg/L | Standard Deviation 0.5633 |
Secondary
Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28
Time frame: Baseline, Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTC299 | Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28 | 0.029 micrograms (µg)/L D-dimer units (DDU) | Standard Deviation 0.9278 |
| Placebo | Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28 | -0.121 micrograms (µg)/L D-dimer units (DDU) | Standard Deviation 0.9392 |
Secondary
Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28
Time frame: Baseline, Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTC299 | Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28 | -0.410 picomoles (pmol)/L | Standard Deviation 0.3096 |
| Placebo | Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28 | -0.497 picomoles (pmol)/L | Standard Deviation 0.3162 |
Secondary
Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28
Time frame: Baseline, Day 28
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTC299 | Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28 | Troponin I | 0.080 µg/L | Standard Deviation 1.5879 |
| PTC299 | Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28 | Troponin T | 0.001 µg/L | Standard Deviation 0.0015 |
| Placebo | Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28 | Troponin T | 0.061 µg/L | Standard Deviation 0.1638 |
| Placebo | Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28 | Troponin I | -0.036 µg/L | Standard Deviation 0.2128 |
Secondary
Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance
Time frame: Baseline, Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTC299 | Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance | 0.000 absorbance (Abs) | Standard Deviation 0.4691 |
| Placebo | Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance | 0.127 absorbance (Abs) | Standard Deviation 0.4218 |
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
Time frame: Baseline, Day 28
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTC299 | 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 | SARS-CoV-2 IgG Antibody Ratio | 0.890 ratio | Standard Deviation 0.6846 |
| PTC299 | 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 | SARS-CoV-2 IgA Antibody Ratio | 0.003 ratio | Standard Deviation 0.6387 |
| Placebo | 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 | SARS-CoV-2 IgA Antibody Ratio | 0.165 ratio | Standard Deviation 0.5122 |
| Placebo | 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 | SARS-CoV-2 IgG Antibody Ratio | 0.874 ratio | Standard Deviation 0.7604 |
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
Time frame: Baseline, Day 28
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTC299 | 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 | SARS-CoV2 v2 NPsw | -1.201 copies/mL | Standard Deviation 0.7503 |
| PTC299 | 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 | Severe Acute Resp Syndrome Coronavirus 2 | -0.432 copies/mL | — |
| Placebo | 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 | SARS-CoV2 v2 | -0.345 copies/mL | Standard Deviation 0.2235 |
| Placebo | 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 | SARS-CoV2 v2 NPsw | 1.532 copies/mL | — |
Secondary
Duration of Hospitalization
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTC299 | Duration of Hospitalization | 8.1 days | Standard Deviation 4.87 |
| Placebo | Duration of Hospitalization | 9.3 days | Standard Deviation 5.49 |
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.
Time frame: Day 28
Population: Safety population included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PTC299 | Number of Mortalities at Day 28 | 6 Participants |
| Placebo | Number of Mortalities at Day 28 | 4 Participants |
Secondary
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
Population: ITT population included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PTC299 | Number of Participants Requiring Invasive Ventilation | 16 Participants |
| Placebo | Number of Participants Requiring Invasive Ventilation | 11 Participants |
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.
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PTC299 | Number of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants Who Did Not Require Supplemental Oxygen at Baseline | 20 Participants |
| Placebo | Number of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants Who Did Not Require Supplemental Oxygen at Baseline | 19 Participants |
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.
Time frame: up to Day 28
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PTC299 | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | RBC | 7 Participants |
| PTC299 | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | Platelets | 21 Participants |
| PTC299 | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | HGB | 9 Participants |
| PTC299 | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | WBC | 22 Participants |
| Placebo | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | RBC | 13 Participants |
| Placebo | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | WBC | 17 Participants |
| Placebo | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | HGB | 13 Participants |
| Placebo | Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline | Platelets | 19 Participants |
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.
Time frame: up to Day 60
Population: Safety population included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PTC299 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 52 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 67 Participants |
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.
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTC299 | Time From Randomization to Cough Reported as Mild or Absent | 3.0 days |
| Placebo | Time From Randomization to Cough Reported as Mild or Absent | 5.0 days |
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.
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTC299 | 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) | 7.0 days |
| Placebo | 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) | 18.0 days |
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.
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTC299 | Time From Randomization to Dyspnea Reported as Mild or Absent | 6.0 days |
| Placebo | Time From Randomization to Dyspnea Reported as Mild or Absent | 5.0 days |
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.
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTC299 | Time From Randomization to Respiratory Rate ≤ 24 Breaths Per Minute on Room Air | 7.0 days |
| Placebo | Time From Randomization to Respiratory Rate ≤ 24 Breaths Per Minute on Room Air | 8.0 days |
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.
Time frame: up to Day 28
Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PTC299 | Time From Randomization to Respiratory Improvement Where Symptom Onset Occurred ≤5 Days | 10.0 days |
| Placebo | Time From Randomization to Respiratory Improvement Where Symptom Onset Occurred ≤5 Days | 28.0 days |
Comparison: Time to respiratory improvement was compared between treatment groups using stratified log-rank test.p-value: 0.033Log Rank