Clinical trial NCT04439071: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19)
Official title: Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Pneumonia
COVID-19
Coronavirus
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-06-19
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Time From Randomization to Respiratory Improvement
timeFrame: up to Day 28
Secondary outcomes:
measure: Number of Participants Requiring Invasive Ventilation
timeFrame: up to Day 28
measure: Number of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants Who Did Not Require Supplemental Oxygen at Baseline
timeFrame: up to Day 28
measure: 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)
timeFrame: up to Day 28
measure: Time From Randomization to Respiratory Rate ≤ 24 Breaths Per Minute on Room Air
timeFrame: up to Day 28
measure: Time From Randomization to Cough Reported as Mild or Absent
timeFrame: up to Day 28
measure: Time From Randomization to Dyspnea Reported as Mild or Absent
timeFrame: up to Day 28
measure: Change From Baseline in Cytokine Levels at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Level of Acute Phase Protein (C Reactive Protein) at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Level of Acute Phase Protein (D-Dimer) at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Level of Acute Phase Protein (Ferritin) at Day 28
timeFrame: Baseline, Day 28
measure: Change From Baseline in Level of Acute Phase Proteins (Troponin I and Troponin T) at Day 28
timeFrame: Baseline, Day 28
measure: Number of Participants With Normalization of Complete Blood Count (CBC) Who Had CBC Out of Range at Baseline
timeFrame: up to Day 28
measure: 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
timeFrame: Baseline, Day 28
measure: Change From Baseline in Viral Load at Day 28: SARS-CoV-2 IgM Antibody Absorbance
timeFrame: Baseline, Day 28
measure: 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
timeFrame: Baseline, Day 28
measure: Duration of Hospitalization
timeFrame: up to Day 28
measure: Number of Mortalities at Day 28
timeFrame: Day 28
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: up to Day 60
Other outcomes:
measure: Time From Randomization to Respiratory Improvement Where Symptom Onset Occurred ≤5 Days
timeFrame: up to Day 28
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Health Care
state: Massachusetts
city: Cleveland
country: United States
facility: University Hospitals Cleveland
state: Ohio
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center
state: South Carolina
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: St. Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Brussels
country: Belgium
facility: St. Pierre University Hospital
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Belo Horizonte
country: Brazil
facility: Hospital Vera Cruz
state: MG
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: RS
city: Joinville
country: Brazil
facility: Centro Hospitalar Unimed (CHU) - Joinville
state: SC
city: Santos
country: Brazil
facility: Hospital Guilherme Alvaro
state: SP
city: Sorocaba
country: Brazil
facility: Hospital Santa Casa de Misecórdia de Sorocoba
state: SP
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: SP
city: São Paulo
country: Brazil
facility: Escola Paulista de Medicina (UNIFESP)
state: SP
city: São Paulo
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SP
city: Bogotá
country: Colombia
facility: Fundación Santa Fe de Bogotá
city: Rionegro
country: Colombia
facility: Centro Cardiovascular Somer Incare
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Irapuato
country: Mexico
facility: Centro Hospitalario MAC
state: Guanajuato
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio Gonzalez
state: Nuevo León
city: Puebla
country: Mexico
facility: Integra RGH Centro de Investigación/ Hospital MAC Puebla
city: Veracruz
country: Mexico
facility: SOMECO - Sociedad de Metabolismo y Corazón S.C.
city: Warsaw
country: Poland
facility: Central Clinic Hospital of the MSWiA in Warsaw
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitário de Lisboa Norte (CHULN), E.P.E - Hospital de Santa Maria
city: Santa Maria da Feira
country: Portugal
facility: Centro Hospitalar de Entre o Douro e Vouga, EPE (CHEDV)
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE (CHVNG/E)
city: Benoni
country: South Africa
facility: Worthwhile Clinical Trials
city: Cape Town
country: South Africa
facility: TREAD Research
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre
city: Durban
country: South Africa
facility: Ahmed Al-Kadi Private Hospital
city: Pretoria
country: South Africa
facility: Global Clinical Trials
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: San Sebastián de los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofía
Study officials:
affiliation: PTC Therapeutics
name: Quintus Ngumah, OD, PhD
role: STUDY_DIRECTOR
References: