Confirmatory study of ataluren in patients with Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 28 November 2016
• Main ID: EUCTR2013-004581-34-BG
• Date of registration: 06/01/2015
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics, Inc.
• Public title: Confirmatory study of ataluren in patients with Cystic Fibrosis
• Scientific title: A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients with Nonsense Mutation Cystic Fibrosis
• Date of first enrolment: 05/02/2015
• Target sample size: 208
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004581-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Denmark, France, Germany, Greece, Israel, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial.
2. Age =6 years.
3. Body weight =16 kg.
4. Sweat chloride >60 mEq/L.
5. Documentation of the presence of a nonsense mutation in at least 1 allele of the CFTR gene, as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization.
6. Verification that a blood sample has been drawn for sequencing of the CFTR gene.
7. Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 =40% and =90% of predicted for age, gender, and height.
8. Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %-predicted FEV1 value.
9. Resting oxygen saturation (as measured by pulse oximetry) =92% on room air.
10. Confirmed screening laboratory values within the central laboratory ranges specified in Table 2 of the protocol.
11. In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period.
12. Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate).
2. Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).
3. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening or any change in acute
therapy between screening and randomization.
4. Chronic use of inhaled or systemic tobramycin within 4 weeks to screening.
5. Exposure to another investigational drug within 4 weeks prior to screening.
6. Ongoing participation in any other therapeutic clinical trial.
7. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening, or between screening and randomization.
8. Treatment with intravenous antibiotics within 3 weeks prior to screening.
9. Ongoing immunosuppressive therapy (other than corticosteroids).
10. Ongoing warfarin, phenytoin, or tolbutamide therapy.
11. History of solid organ or hematological transplantation.
12. Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening.
13. Known portal hypertension.
14. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
15. Pregnancy or breast-feeding.
16. Current smoker or a smoking history of =10 pack-years (number of cigarette packs/day × number of years smoked).
17. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Nonsense Mutation Cystic Fibrosis
MedDRA version: 19.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Absolute change in %-predicted FEV1 at Week 48, defined as the average between the change at Week 40 and that at Week 48 (by spirometry)

Timepoint(s) of evaluation of this end point: Screening, Week 1 to Week 48, 4-Week Post-Treatment follow-up

Main Objective: To evaluate the ability of ataluren to improve pulmonary function relative to placebo

Secondary Objective: To determine the effect of ataluren on:
1. Pulmonary symptoms
2. General well-being
3. Health-related Quality of Life (HRQL)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1: Week 1 to Week 48
2: Screening, Week 1 to Week 48, 4-Week Post-Treatment follow-up
3: Screening, Week 1 to Week 48

Secondary end point(s): 1. Rate of pulmonary exacerbations (expanded Fuchs criteria)
2. Change from baseline in Body Mass Index (BMI)
3. Respiratory HRQL as assessed by the Cystic Fibrosis Questionnaire - Revised (CFQ-R) respiratory domain

Secondary ID(s)

PTC124-GD-021-CF

2013-004581-34-IT

48,648

Source(s) of Monetary Support

PTC Therapeutics, Inc.