Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)

• Sponsor: PTC Therapeutics
• Collaborators: Cystic Fibrosis Foundation; European Cystic Fibrosis Society-Clinical Trial Network (ECFS-CTN)
• Information provided by (Responsible Party): PTC Therapeutics

Study Description

Brief Summary:

This is a Phase 3, international, multicenter, randomized, double-blind, placebo-controlled, efficacy and safety study of ataluren in patients with nonsense mutation cystic fibrosis (nmCF) not receiving chronic inhaled aminoglycosides.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Ataluren (PTC124®); Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	208 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients With Nonsense Mutation Cystic Fibrosis
Study Start Date :	June 2014
Estimated Primary Completion Date :	November 2016
Estimated Study Completion Date :	November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ataluren (PTC124®); Oral powder for suspension taken 3 times per day (10-, 10-, and 20-mg/kg morning, midday and evening, respectively) for 48 weeks	Drug: Ataluren (PTC124®)
Placebo Comparator: Placebo; Matching placebo taken 3 times per day for 48 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. FEV1 by spirometry [ Time Frame: 48 weeks ]

Secondary Outcome Measures :

1. Rate of pulmonary exacerbations (modified Fuchs criteria) [ Time Frame: 48 weeks ]
2. Respiratory HRQL as assessed by the CFQ-R respiratory domain [ Time Frame: 48 weeks ]
3. Body weight and BMI [ Time Frame: 48 weeks ]

Other Outcome Measures:

1. FVC and FEF25-75 by spirometry [ Time Frame: 48 weeks ]
2. Incidence and duration of pulmonary exacerbations [ Time Frame: 48 weeks ]
3. Other HRQL domains as assessed by the CFQ-R [ Time Frame: 48 weeks ]
4. Concentrations of liver enzyme tests (AST, ALT, GGT) [ Time Frame: 48 weeks ]
5. Fecal calprotectin level [ Time Frame: 48 weeks ]
6. New Pseudomonas aeruginosa lung infection [ Time Frame: 48 weeks ]
7. Safety profile characterized by type, frequency, severity, timing, and relationship to study drug of treatment-emergent adverse events, laboratory abnormalities, and ECG abnormalities [ Time Frame: 48 weeks ]
8. Study drug compliance as assessed by quantification of unused study drug [ Time Frame: 48 weeks ]
9. Trough ataluren plasma concentrations [ Time Frame: 48 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	6 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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
• Age >=6 years.
• Body weight >=16 kg.
• Sweat chloride >60 mEq/L
• 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
• Verification that a blood sample has been drawn for sequencing of the CFTR gene
• Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 >=40% and <=90% of predicted
• Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening % predicted FEV1 value
• Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.
• Confirmed screening laboratory values within pre-specified ranges
• 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
• Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions

Exclusion Criteria:

• Known hypersensitivity to any of the ingredients or excipients of the study drug
• Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).
• 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
• Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled aminoglycosides within 4 months prior to screening.
• Exposure to another investigational drug within 4 weeks prior to screening
• Ongoing participation in any other therapeutic clinical trial
• Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening
• Treatment with intravenous antibiotics within 3 weeks prior to screening
• Ongoing immunosuppressive therapy (other than corticosteroids)
• Ongoing warfarin, phenytoin, or tolbutamide therapy
• History of solid organ or hematological transplantation
• Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening
• Known portal hypertension
• Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test
• Pregnancy or breast-feeding
• Current smoker or a smoking history of >=10 pack-years (number of cigarette packs/day x number of years smoked).
• 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

Contacts and Locations

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Sponsors and Collaborators

PTC Therapeutics

Cystic Fibrosis Foundation

European Cystic Fibrosis Society-Clinical Trial Network (ECFS-CTN)

Investigators

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Study Director:	Joseph McIntosh, MD	PTC Therapeutics

More Information

Additional Information:

Related Info 

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Responsible Party:	PTC Therapeutics
ClinicalTrials.gov Identifier:	NCT02139306 History of Changes
Other Study ID Numbers:	PTC124-GD-021-CF; 2013-004581-34 ( EudraCT Number )
First Posted:	May 15, 2014
Last Update Posted:	November 26, 2015
Last Verified:	November 2015

Additional relevant MeSH terms:

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Fibrosis; Cystic Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases	Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases