Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)
A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients With Nonsense Mutation Cystic Fibrosis
2 other identifiers
interventional
279
16 countries
88
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2014
88 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2014
CompletedFirst Posted
Study publicly available on registry
May 15, 2014
CompletedStudy Start
First participant enrolled
August 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2016
CompletedResults Posted
Study results publicly available
May 14, 2020
CompletedMay 14, 2020
May 1, 2020
2.3 years
May 13, 2014
May 30, 2017
May 4, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48
The FEV1 is the volume of air forcibly exhaled in one second and is measured using forced expiratory air spirometry. Change in ppFEV1 at Week 48 was defined as the average between the change from baseline at Week 40 and that at Week 48. Baseline for ppFEV1 was defined as an average of ppFEV1 at Screening (Weeks -4 to -1) and Baseline (Day 1) visits.
From Baseline to Week 48
Secondary Outcomes (9)
48-week Rate of Pulmonary Exacerbations
Week 48
Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48
Baseline (Day 1) and Week 48
Change From Baseline in Body Mass Index (BMI) at Week 48
Baseline (Day 1) and Week 48
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
Number of Participants With TEAEs by Severity and Relationship to Study Drugs
From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
- +4 more secondary outcomes
Study Arms (2)
Ataluren (PTC124®)
EXPERIMENTALParticipants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
Placebo
PLACEBO COMPARATORParticipants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Interventions
Eligibility Criteria
You may qualify if:
- 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 milliequivalent per liter (mEq/L)
- Documentation of the presence of a nonsense mutation in at least 1 allele of the cystic fibrosis transmembrane conductance regulator (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
You may not qualify if:
- 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 Cystic Fibrosis (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 weeks 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- PTC Therapeuticslead
- Cystic Fibrosis Foundationcollaborator
- ECFS-Clinical Trial Network (ECFS-CTN)collaborator
Study Sites (88)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Pulmonary Associates of Mobile PC
Mobile, Alabama, 36608, United States
Miller Children's Hospital Long Beach
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital and Research Center at Oakland
Oakland, California, 94609, United States
Stanford University-Children's Hospital
Palo Alto, California, 94304, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Nemours Children's Clinic
Jacksonville, Florida, 32207, United States
University of Miami
Miami, Florida, 33136, United States
Miami Children's Hospital
Miami, Florida, 33155, United States
All Children's Hospital
St. Petersburg, Florida, 33701, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Children's Hospital Boston
Boston, Massachusetts, 02115, United States
Washington University
St Louis, Missouri, 63110, United States
Monmouth Medical Center
Long Branch, New Jersey, 07740, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Beth Israel Medical Center
New York, New York, 10003, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Columbia University Medical Center
New York, New York, 10032, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
University of Cincinnati
Cincinnati, Ohio, 45221, United States
Rainbow Babies & Children's Hospital
Cleveland, Ohio, 44106, United States
Santiago Reyes, MD
Oklahoma City, Oklahoma, 73112, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19129, United States
Texas Children's Hospital
Houston, Texas, 77094, United States
University of Texas Health Science Center
Tyler, Texas, 75708, United States
Childrens Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital Universitario Austral
Buenos Aires, B1629ODT, Argentina
Hospital de Niños Dr. Ricardo Gutiérrez
Buenos Aires, C1425EFD, Argentina
Hospital de Niños Superiora Sor Maria Ludovica
La Plata, 1900, Argentina
Royal Adelaide Hospital
Adelaide, 5000, Australia
Prince Charles Hospital
Chermside, 4032, Australia
Princess Margaret Hospital
Perth, 6840, Australia
Hôpital Universitaire des Enfants Reine Fabiola
Brussels, 1020, Belgium
University Hospital Brussels
Brussels, 1090, Belgium
University Hospital Leuven
Leuven, 3000, Belgium
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul
Porto Alegre, Brazil
Instituto da Criança - Hospital das Clínicas
São Paulo, 05403-000, Brazil
University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
Plovdiv, Bulgaria
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
Sofia, Bulgaria
Clinical Research Institute of Montreal
Montreal, H2W 1R7, Canada
CHU de Quebec - Hopital CHUL
Québec, G1V 4G2, Canada
University of Toronto Hospital for Sick Children
Toronto, M5G 1X8, Canada
British Columbia Children's Hospital
Vancouver, V6H 3V4, Canada
Hôpital Femme-Mère-Enfant
Bron, 69677, France
Hôpital Arnaud de Villeneuve
Montpellier, 34295, France
Hôpital Necker-Enfants Malades
Paris, 75015, France
Centre de Perharidy
Roscoff, 29684, France
Centre Hospitalier Regional Sud Reunion
Saint-Pierre, 97448, France
Charité Universitätsmedizin Berlin
Berlin, 13353, Germany
St. Josef Hospital GmbH
Bochum, 44791, Germany
Universitätsklinikum Köln
Cologne, 50937, Germany
Christiane Herzog CF-Zentrum
Frankfurt am Main, 60590, Germany
Universitätsklinikum Jena
Jena, 07745, Germany
LMU Klinikum der Universität München
München, 80336, Germany
Dr. Von Haunersches Kinderspital
München, 80337, Germany
General Hospital of Thessaloniki Ippokration
Thessaloniki, Greece
Meyer Children's Hospital
Haifa, 31096, Israel
Hadassah University Hospital
Jerusalem, 91240, Israel
Ospedali Riuniti di Ancona
Ancona, 60123, Italy
Azienda Ospedaliera A Meyer
Florence, 50139, Italy
Lombardia Cystic Fibrosis Center
Milan, 20122, Italy
Ospedale Pediatrico Bambino Gesù IRCCS
Roma, Italy
Azienda Policlinico Umberto I
Rome, 00161, Italy
University of Verona
Verona, 37126, Italy
Radboud University
Nijmegen, 6525 GA, Netherlands
Erasmus MC
Rotterdam, Netherlands
Hagaziekenhuis
The Hague, 2491, Netherlands
Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku
Gdansk, Poland
NZOZ Sanatorium Cassia-Villa Medica
Rabka-Zdrój, 34-700, Poland
NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
Rzeszów, 35-612, Poland
Instytut Matki I Dziecka
Warsaw, 01-211, Poland
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Hospital University
Barcelona, 08035, Spain
Hospital Sant Joan de Deu
Esplugues de Llobregat, 08950, Spain
Hospital Regional Universitario de Malaga
Málaga, Spain
Hospital de Sabadell, Consorci Sanitari Parc Tauli
Sabadell, 08208, Spain
Hospital Universitario Virgen del Rocio
Seville, Spain
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, United Kingdom
Heart of England NHS Foundation Trust
Birmingham, United Kingdom
Southern General Hospital
Glasgow, G120YN, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Royal Brompton Hospital
London, United Kingdom
Llandough Hospital
Penarth, CF64 2XX, United Kingdom
Southampton University Hospitals NHS Trust
Southampton, United Kingdom
Related Publications (3)
Aslam AA, Sinha IP, Southern KW. Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis. Cochrane Database Syst Rev. 2023 Mar 3;3(3):CD012040. doi: 10.1002/14651858.CD012040.pub3.
PMID: 36866921DERIVEDVanDevanter DR, Hamblett NM, Simon N, McIntosh J, Konstan MW. Evaluating assumptions of definition-based pulmonary exacerbation endpoints in cystic fibrosis clinical trials. J Cyst Fibros. 2021 Jan;20(1):39-45. doi: 10.1016/j.jcf.2020.07.008. Epub 2020 Jul 15.
PMID: 32682670DERIVEDKonstan MW, VanDevanter DR, Rowe SM, Wilschanski M, Kerem E, Sermet-Gaudelus I, DiMango E, Melotti P, McIntosh J, De Boeck K; ACT CF Study Group. Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: The international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF). J Cyst Fibros. 2020 Jul;19(4):595-601. doi: 10.1016/j.jcf.2020.01.007. Epub 2020 Jan 23.
PMID: 31983658DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Joseph McIntosh
- Organization
- PTC Therapeutics, Inc
Study Officials
- STUDY DIRECTOR
Joseph McIntosh, MD
PTC Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2014
First Posted
May 15, 2014
Study Start
August 1, 2014
Primary Completion
November 1, 2016
Study Completion
November 1, 2016
Last Updated
May 14, 2020
Results First Posted
May 14, 2020
Record last verified: 2020-05
Data Sharing
- IPD Sharing
- Will not share