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

COVID-19 Clinical Trial

— FITE19  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04439071
• Other study ID #: PTC299-VIR-015-COV19
• Secondary ID: 2020-001872-13
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: July 9, 2020
• Est. completion date: July 20, 2022

Study information

• Verified date: May 2023
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 189
• Est. completion date: July 20, 2022
• Est. primary completion date: July 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections
• COVID-19
• Pneumonia

Intervention

Drug:
• PTC299
Oral tablets

Other:
• SOC
As defined per local written policies or guidelines.

Drug:
• Placebo
Oral tablets

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Sunshine Hospital	St. Albans	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	St. Pierre University Hospital	Brussels
Belgium	Clinique Saint Pierre	Ottignies
Brazil	Hospital Vera Cruz	Belo Horizonte	MG
Brazil	Centro Hospitalar Unimed (CHU) - Joinville	Joinville	SC
Brazil	Hospital Moinhos de Vento	Porto Alegre	RS
Brazil	Hospital Guilherme Alvaro	Santos	SP
Brazil	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 Alemao Oswaldo Cruz	São Paulo	SP
Brazil	Hospital Santa Casa de Misecórdia de Sorocoba	Sorocaba	SP
Colombia	Fundación Santa Fe de Bogotá	Bogotá
Colombia	Centro Cardiovascular Somer Incare	Rionegro
France	Hôpital Pitié-Salpêtrière	Paris
Mexico	Centro Hospitalario MAC	Irapuato	Guanajuato
Mexico	Hospital Universitario Dr. José Eleuterio Gonzalez	Monterrey	Nuevo León
Mexico	Integra RGH Centro de Investigación/ Hospital MAC Puebla	Puebla
Mexico	SOMECO - Sociedad de Metabolismo y Corazón S.C.	Veracruz
Poland	Central Clinic Hospital of the MSWiA in Warsaw	Warsaw
Portugal	Centro Hospitalar Universitário de Lisboa Norte (CHULN), E.P.E - Hospital de Santa Maria	Lisboa
Portugal	Centro Hospitalar de Entre o Douro e Vouga, EPE (CHEDV)	Santa Maria da Feira
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE (CHVNG/E)	Vila Nova de Gaia
South Africa	Worthwhile Clinical Trials	Benoni
South Africa	Tiervlei Trial Centre	Cape Town
South Africa	TREAD Research	Cape Town
South Africa	Ahmed Al-Kadi Private Hospital	Durban
South Africa	Global Clinical Trials	Pretoria
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitario de Bellvitge	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Infanta Sofía	San Sebastián de los Reyes
United States	Augusta University	Augusta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Ralph H. Johnson VA Medical Center	Charleston	South Carolina
United States	University Hospitals Cleveland	Cleveland	Ohio
United States	University of California, Irvine	Orange	California
United States	University of Massachusetts Memorial Health Care	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Colombia,  France,  Mexico,  Poland,  Portugal,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
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.	up to Day 28
Secondary	Number of Participants Requiring Invasive Ventilation	Number of participants requiring invasive ventilation at any time during the study were reported.	up to Day 28
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.	up to Day 28
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.	up to Day 28
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.	up to Day 28
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.	up to Day 28
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.	up to Day 28
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.	Baseline, Day 28
Secondary	Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28		Baseline, Day 28
Secondary	Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28		Baseline, Day 28
Secondary	Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28		Baseline, Day 28
Secondary	Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28		Baseline, Day 28
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.	up to Day 28
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		Baseline, Day 28
Secondary	Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance		Baseline, Day 28
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		Baseline, Day 28
Secondary	Duration of Hospitalization		up to Day 28
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.	Day 28
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.	up to Day 60

External Links

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