A Phase 3 Efficacy and Safety Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 19 November 2012
• Main ID: EUCTR2008-003924-52-SE
• Date of registration: 17/12/2008
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics, Inc
• Public title: A Phase 3 Efficacy and Safety Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
• Scientific title: A Phase 3 Efficacy and Safety Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
• Date of first enrolment: 08/04/2009
• Target sample size: 208
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003924-52
• 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

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Institutional Ethics Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the subject should be followed.
2. Age =6 years.
3. Body weight =16 kg.
4. Abnormal nasal TEPD total chloride conductance (a less electrically negative value than -5 mV for total chloride conductance [?chloride-free+isoproterenol]). Note: Even if a subject has past documentation of an abnormal TEPD, a TEPD must be performed as part of the screening procedures, must show an adequate tracing in at least 1 nostril, and must be abnormal (taken as a mean of both nostrils if values for both nostrils are available).
5. Sweat chloride >40 mEq/L. Note: A patient does not need to have a repeat sweat test solely for enrollment into this study if documentation of a sweat chloride value>40 mEq/L is already available. However, prior to randomization, all patients must have a baseline sweat chloride test sample collected using study-specific procedures.
6. 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.
7. Verification that a blood sample has been drawn for sequencing of the CFTR gene. Note: A subject who has written documentation of a nonsense mutation as the cause of CF need not wait for confirmatory results to start study drug as long as the confirmatory blood sample for gene sequencing has been drawn.
8. 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 [Wang 1993, Hankinson 1999].
9. Resting oxygen saturation (as measured by pulse oximetry) =92% on room air.
10. Documentation by VivoMetrics that the subject has satisfactorily completed a 24-hour LifeShirt® cough frequency assessment.
11. Confirmed screening laboratory values within the central laboratory ranges specified in Table 2 below. Note: Confirmation should be performed for out-of-range values to determine if the abnormality is real or artifactual. Values used to establish eligibility should be obtained within the 4-week screening period, and should generally be the most recent measurement obtained.
12. 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 within 60 days of the last administration of the study drug.
13. Willingness and ability to comply with scheduled visits, drug administration plan, study restrictions, and study procedures (including TEPD testing, spirometry, LifeShirt® evaluations, renal ultrasound, CT scan, and laboratory tests). Note: Psychological, social, familial, or geographical factors that might preclude adequate study par
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. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to start of study treatment. Note: A subject can be enrolled who is using inhaled medications such as aztreonam, tobramycin, dornase-alfa, hypertonic saline, corticosteroids, or ß2 agonists; or systemic drugs such as azithromycin or ibuprofen. Expected cycling of inhaled aztreonam or inhaled tobramycin (or similar inhaled aminoglycoside) is permitted. Other than for treatment of CF pulmonary exacerbations, subjects should remain on a stable medical regimen of treatment/prophylaxis for CF-related conditions to avoid confounding interpretation of study results.
3. Exposure to another investigational drug within 4 weeks prior to start of study treatment. Note: Subjects receiving another investigational drug as part of a pre-approval expanded access program for that drug may participate with the prior consent of the PTC Therapeutics medical monitor.
4. Ongoing participation in any other therapeutic clinical trial. Note: Subjects receiving
another investigational drug as part of a pre-approval expanded access program for that drug may participate with the prior consent of the PTC Therapeutics medical monitor.
5. Treatment with systemic aminoglycoside antibiotics within 2 weeks prior to the date of the baseline TEPD assessment.
6. Treatment with intravenous antibiotics within 3 weeks prior to start of study treatment.
7. Ongoing immunosuppressive therapy (other than corticosteroids).
8. Ongoing warfarin, phenytoin, or tolbutamide therapy.
9. History of solid organ or hematological transplantation.
10. Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to start of study treatment.
11. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to randomization.
12. Known portal hypertension.
13. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
14. Pregnancy or breast-feeding.
15. Current smoker or a smoking history of =10 pack-years (number of cigarette packs/day × number of years smoked).
16. 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.
17. History of Grade =3 creatinine elevation due to aminoglycoside nephrotoxicity.


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

Health Condition(s) or Problem(s) studied

Nonsense-Mutation-Mediated Cystic Fibrosis
MedDRA version: 9.1 Level: LLT Classification code 10011762 Term: Cystic fibrosis

Intervention(s)

Product Name: PTC124
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Other descriptive name: PTC-0161480; PTC-124; Compound 1a; RPS 2505; PTC-C124; 291844
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: PTC124
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Other descriptive name: PTC-0161480; PTC-124; Compound 1a; RPS 2505; PTC-C124; 291844
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: PTC124
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Other descriptive name: PTC-0161480; PTC-124; Compound 1a; RPS 2505; PTC-C124; 291844
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)

Secondary Objective: The secondary objectives of the trial are to confirm and extend perspectives on complications of CF through evaluation of pulmonary symptoms and exacerbations, cough, and subject or parent/caregiver perception of respiratory functioning.

Primary end point(s): The primary efficacy endpoint is the relative change in %-predicted FEV1 measured by spirometry from Baseline to Week 48.

The safety endpoints:
-Safety profile characterize by type, frequency, severity, timing and relationship to study drug of treatment-emergent adverse events, laboratory abnomalities, or ECG abnormalities,
-Subject compliance log and quantification of used and unused study drug
-Trough and peak (2-jour samples) of PTC124 plasma concentrations as assessed by a validated bioanalytical method

Main Objective: The main objective is to evaluate the ability of PTC124 to improve pulmonary function as assessed by FEV1.

Secondary ID(s)

PTC124-GD-009-CF