A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19)
- Conditions
- PneumoniaCOVID-19Coronavirus
- Interventions
- Registration Number
- NCT04439071
- Lead Sponsor
- PTC Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 189
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Signed and dated informed consent document(s).
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Agrees to the collection of nasopharyngeal swabs and venous blood and all other protocol-specified procedures.
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Male or non-pregnant female adult ≥18 years of age at time of enrollment.
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Hospitalized and has laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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Symptom onset was ≤10 days prior to screening.
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Has oxygen saturation SpO2 <94% on room air.
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Has at least one of a respiratory rate >24 breaths/minute or cough.
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Lung involvement as confirmed by radiographic infiltrates observed on imaging (chest X-ray, computed tomography (CT) scan, or an equivalent test).
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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).
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PTC299 + Standard of Care (SOC) PTC299 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. PTC299 + Standard of Care (SOC) SOC 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. Placebo + SOC SOC 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. Placebo + SOC Placebo 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance Baseline, 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 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.
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 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 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.
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 Number of Participants Requiring Invasive Ventilation up to Day 28 Number of participants requiring invasive ventilation at any time during the study were reported.
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.
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 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.
Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28 Baseline, Day 28 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.
Trial Locations
- Locations (41)
University of Massachusetts Memorial Health Care
🇺🇸Worcester, Massachusetts, United States
Fundación Santa Fe de Bogotá
🇨🇴Bogotá, Colombia
Clinique Saint Pierre
🇧🇪Ottignies, Belgium
Augusta University
🇺🇸Augusta, Georgia, United States
University Hospitals Cleveland
🇺🇸Cleveland, Ohio, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Centro Hospitalario MAC
🇲🇽Irapuato, Guanajuato, Mexico
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital Universitario de Bellvitge
🇪🇸Barcelona, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
University of California, Irvine
🇺🇸Orange, California, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
St. Pierre University Hospital
🇧🇪Brussels, Belgium
Sunshine Hospital
🇦🇺St. Albans, Victoria, Australia
Hospital Vera Cruz
🇧🇷Belo Horizonte, MG, Brazil
Hospital Guilherme Alvaro
🇧🇷Santos, SP, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷São Paulo, SP, Brazil
Hôpital Pitié-Salpêtrière
🇫🇷Paris, France
SOMECO - Sociedad de Metabolismo y Corazón S.C.
🇲🇽Veracruz, Mexico
Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE (CHVNG/E)
🇵🇹Vila Nova de Gaia, Portugal
Centro Hospitalar de Entre o Douro e Vouga, EPE (CHEDV)
🇵🇹Santa Maria da Feira, Portugal
TREAD Research
🇿🇦Cape Town, South Africa
Tiervlei Trial Centre
🇿🇦Cape Town, South Africa
Global Clinical Trials
🇿🇦Pretoria, South Africa
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Ahmed Al-Kadi Private Hospital
🇿🇦Durban, South Africa
Ralph H. Johnson VA Medical Center
🇺🇸Charleston, South Carolina, United States
Hospital Moinhos de Vento
🇧🇷Porto Alegre, RS, Brazil
Worthwhile Clinical Trials
🇿🇦Benoni, South Africa
Centro Hospitalar Unimed (CHU) - Joinville
🇧🇷Joinville, SC, Brazil
Hospital Santa Casa de Misecórdia de Sorocoba
🇧🇷Sorocaba, SP, Brazil
Hospital Universitario Infanta Sofía
🇪🇸San Sebastián de los Reyes, Spain
Escola Paulista de Medicina (UNIFESP)
🇧🇷São Paulo, SP, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷São Paulo, SP, Brazil
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Centro Cardiovascular Somer Incare
🇨🇴Rionegro, Colombia
Integra RGH Centro de Investigación/ Hospital MAC Puebla
🇲🇽Puebla, Mexico
Centro Hospitalar Universitário de Lisboa Norte (CHULN), E.P.E - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Hospital Universitario Dr. José Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo León, Mexico
Central Clinic Hospital of the MSWiA in Warsaw
🇵🇱Warsaw, Poland