E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
Coronavirus disease 2019 (COVID-19) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084380 |
E.1.2 | Term | COVID-19 pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the clinical efficacy of PTC299 compared with placebo assessed by time to respiratory improvement in adult subjects hospitalized with COVID-19. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the clinical efficacy of PTC299 compared with placebo, as assessed by respiratory function, immune response, length of hospitalization, and mortality. • To evaluate the safety of PTC299 as assessed by drug related adverse events. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject (or legally authorized representative) is willing and able to provide informed consent and comply with all protocol requirements. 2. Agrees to the collection of nasopharyngeal swabs and venous blood and all other protocol-specified procedures. 3. Male or non-pregnant female adult ≥18 years of age at time of enrollment. 4. Hospitalized and has laboratory-confirmed infection with SARS-CoV-2. 5. Symptom onset was ≤10 days prior to Screening 6. Has SpO2 <94% on room air 7. Has at least one of respiratory rate >24 breaths/minute or cough 8. Lung involvement as confirmed by radiographic infiltrates observed on imaging (chest X-ray, CT scan, or an equivalent test) 9. 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 one primary form of the following of 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 (acceptable methods will be determined by the site).: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: - oral - intravaginal - transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: - oral - injectable - implantable • intrauterine device • intrauterine hormone-releasing system • 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 (eg, bilateral tubal ligation, hysterectomy, bilateral oophorectomy). 10. 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. |
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E.4 | Principal exclusion criteria |
1. Requires mechanical ventilation 2. Current participation in any other interventional study. 3. Severe liver disease as defined by alanine transaminase/aspartate transaminase levels (ALT/AST) >4 times the upper limit of normal. 4. Lymphocyte count <500 lymphocytes/µL or hemoglobin <11.0 g/dL 5. Stage 4 severe chronic kidney disease or requiring dialysis (ie, estimated glomerular filtration rate <30) 6. Any other condition, that in the opinion of the investigator, may be cause to exclude the subject from the study. 7. Use of steroids (except dexamethasone), drugs metabolized by CYP2D6, CYP2C inducers, IL-6 neutralizing antibodies, IL-6 receptor inhibitors, or any investigational therapy. 8. Pregnancy or breast feeding. 9. Anticipated transfer to another hospital which is not a study site within 72 hours. 10. Known allergy to PTC299 or excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time from randomization to respiratory improvement, defined as peripheral oxygen saturation (SpO2) ≥94% on room air sustained until discharge from the hospital or the end of the study (Day 28). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint is time from randomization to respiratory improvement, defined as SpO2 ≥94% on room air sustained until discharge from the hospital or the end of the study (Day 28). |
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E.5.2 | Secondary end point(s) |
● The proportion of subjects requiring invasive ventilation at any point during the study ● The proportion of subjects requiring supplemental oxygen or non-invasive ventilation at any point during the study in subjects who did not require supplemental oxygen at baseline ● Time from randomization to defervescence in subjects presenting with fever at enrollment (temperature of ≥37.6 °C axilla, ≥38.0 °Coral, or ≥38.6 °C tympanic or rectal) ● Time from randomization to respiratory rate ≤24 breaths/minute on room air ● Time from randomization to cough reported as mild or absent (in those with cough at enrollment rated severe or moderate) ● Time from randomization to dyspnea reported as mild or absent (on a scale of severe, moderate, mild, absent, in those with dyspnea at enrollment rated as severe or moderate) ● Attenuation of immune responses as indicated by: ○ reduction in cytokine levels, potentially including interleukin (IL)-2, IL-6, IL 7, IL-17, G-CSF, IP-10, MCP-1, MIP1-α, and TNF-α ○ reduction in levels of acute phase proteins, potentially including ferritin, C reactive protein, D-dimer, and cardiac troponin ○ normalization in the complete blood count ● Changes in other laboratory parameters potentially including decreases in lactate dehydrogenase, prothrombin time, albumin ● Reduction in viral load ● Duration of hospitalization measured in days ● Mortality at Day 28 ● Overall safety profile characterized by type, frequency, severity, timing, and relationship to study treatment of any adverse events (AEs) or laboratory abnormalities. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Similar to the primary endpoint, Kaplan-Meier estimate, median and rate at Days 7, 14, and 28 will be presented for overall survival, time from randomization to defervescence, time from randomization to respiratory rate ≤24 breaths/minute on room air, time from randomization to cough reported as mild or absent (in those with cough at enrollment rated severe or moderate), and time from randomization to dyspnea reported as mild or absent (on a scale of severe, moderate, mild, absent, in those with dyspnea at enrollment rated as severe or moderate). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Mexico |
United States |
Belgium |
France |
Italy |
Poland |
Portugal |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will end when the last subject has completed the final assessment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |