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Cystic FibrosisPhase 3NCT02139306

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

A Phase 3 study testing Ataluren (PTC124®) in people with Cystic Fibrosis, run by PTC Therapeutics at 88 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 6 years and older
Conditions the study is for
Cystic Fibrosis
What is being tested?
Ataluren (PTC124®)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
279 participants
Where
88 sitesin 16 countries
Study dates
Aug 2014to Nov 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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, electrocardiogram (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

Trial locations and contacts

88 sites in 16 countries.

88 sites in 16 countries

United States30 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Children's Hospital Boston

    Boston, Massachusetts, 02115

  • Ann and Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • University of Cincinnati

    Cincinnati, Ohio, 45221

  • Rainbow Babies & Children's Hospital

    Cleveland, Ohio, 44106

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Texas Children's Hospital

    Houston, Texas, 77094

  • Indiana University

    Indianapolis, Indiana, 46202

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • Miller Children's Hospital Long Beach

    Long Beach, California, 90806

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Miami

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Childrens Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Pulmonary Associates of Mobile PC

    Mobile, Alabama, 36608

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Beth Israel Medical Center

    New York, New York, 10003

  • New York University Langone Medical Center

    New York, New York, 10016

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609

  • Santiago Reyes, MD

    Oklahoma City, Oklahoma, 73112

  • Stanford University-Children's Hospital

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Drexel University College of Medicine

    Philadelphia, Pennsylvania, 19129

  • Washington University

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • University of Texas Health Science Center

    Tyler, Texas, 75708

Other trials in United States

Germany7 sites

  • Charité Universitätsmedizin Berlin

    Berlin, 13353

  • St. Josef Hospital GmbH

    Bochum, 44791

  • Universitätsklinikum Köln

    Cologne, 50937

  • Christiane Herzog CF-Zentrum

    Frankfurt am Main, 60590

  • Universitätsklinikum Jena

    Jena, 07745

  • LMU Klinikum der Universität München

    München, 80336

  • Dr. Von Haunersches Kinderspital

    München, 80337

Other trials in Germany

United Kingdom7 sites

  • Birmingham Children's Hospital NHS Foundation Trust

    Birmingham

  • Heart of England NHS Foundation Trust

    Birmingham

  • Southern General Hospital

    Glasgow, G120YN

  • St James's University Hospital

    Leeds

  • Royal Brompton Hospital

    London

  • Llandough Hospital

    Penarth, CF64 2XX

  • Southampton University Hospitals NHS Trust

    Southampton

Other trials in United Kingdom

Italy6 sites

  • Ospedali Riuniti di Ancona

    Ancona, 60123

  • Azienda Ospedaliera A Meyer

    Florence, 50139

  • Lombardia Cystic Fibrosis Center

    Milan, 20122

  • Ospedale Pediatrico Bambino Gesù IRCCS

    Roma

  • Azienda Policlinico Umberto I

    Rome, 00161

  • University of Verona

    Verona, 37126

Other trials in Italy

Spain6 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital University

    Barcelona, 08035

  • Hospital Sant Joan de Deu

    Esplugues de Llobregat, 08950

  • Hospital Regional Universitario de Malaga

    Málaga

  • Hospital de Sabadell, Consorci Sanitari Parc Tauli

    Sabadell, 08208

  • Hospital Universitario Virgen del Rocio

    Seville

Other trials in Spain

France5 sites

  • Hôpital Femme-Mère-Enfant

    Bron, 69677

  • Hôpital Arnaud de Villeneuve

    Montpellier, 34295

  • Hôpital Necker-Enfants Malades

    Paris, 75015

  • Centre de Perharidy

    Roscoff, 29684

  • Centre Hospitalier Regional Sud Reunion

    Saint-Pierre, 97448

Other trials in France

Canada4 sites

  • Clinical Research Institute of Montreal

    Montreal, H2W 1R7

  • CHU de Quebec - Hopital CHUL

    Québec, G1V 4G2

  • University of Toronto Hospital for Sick Children

    Toronto, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, V6H 3V4

Other trials in Canada

Poland4 sites

  • Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku

    Gdansk

  • NZOZ Sanatorium Cassia-Villa Medica

    Rabka-Zdrój, 34-700

  • NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii

    Rzeszów, 35-612

  • Instytut Matki I Dziecka

    Warsaw, 01-211

Other trials in Poland

Argentina3 sites

  • Hospital Universitario Austral

    Buenos Aires, B1629ODT

  • Hospital de Niños Dr. Ricardo Gutiérrez

    Buenos Aires, C1425EFD

  • Hospital de Niños Superiora Sor Maria Ludovica

    La Plata, 1900

Other trials in Argentina

Australia3 sites

  • Royal Adelaide Hospital

    Adelaide, 5000

  • Prince Charles Hospital

    Chermside, 4032

  • Princess Margaret Hospital

    Perth, 6840

Other trials in Australia

Belgium3 sites

  • Hôpital Universitaire des Enfants Reine Fabiola

    Brussels, 1020

  • University Hospital Brussels

    Brussels, 1090

  • University Hospital Leuven

    Leuven, 3000

Other trials in Belgium

Netherlands3 sites

  • Radboud University

    Nijmegen, 6525 GA

  • Erasmus MC

    Rotterdam

  • Hagaziekenhuis

    The Hague, 2491

Other trials in Netherlands

Brazil2 sites

  • Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul

    Porto Alegre

  • Instituto da Criança - Hospital das Clínicas

    São Paulo, 05403-000

Other trials in Brazil

Bulgaria2 sites

  • University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD

    Plovdiv

  • University Multiprofile Hospital for Active Treatment Aleksandrovska EAD

    Sofia

Other trials in Bulgaria

Israel2 sites

  • Meyer Children's Hospital

    Haifa, 31096

  • Hadassah University Hospital

    Jerusalem, 91240

Other trials in Israel

Greece1 site

  • General Hospital of Thessaloniki Ippokration

    Thessaloniki

Other trials in Greece

About this study

Official title: A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients With Nonsense Mutation Cystic Fibrosis

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.

Read the detailed description

This study is to enroll 208 subjects (184 fully evaluable) with nonsense-mutation-mediated CF who are at least 6 years of age and have an forced expiratory volume in 1 second (FEV1) >= 40% and <= 90% of predicted. Subjects will be stratified based on age, inhaled antibiotic use, and baseline FEV1, and will be randomized in a 1:1 ratio to receive oral ataluren administered 3 times per day (TID) at respective morning, midday, and evening doses of 10-, 10-, and 20-mg/kg or placebo. Based on the results of a previously conducted study, patients treated with chronic inhaled aminoglycosides (including TOBI) will not be eligible for participation. Spirometry measurement at the screening visit will establish patient eligibility for inclusion based on lung function. FEV1 stability will be assessed during the approximately 4-week screening period, at the conclusion of which patients will be required to demonstrate a relative change in %-predicted FEV1 of less than 15% when compared to the screening value. Assessments will be performed every 8 weeks, depending upon the outcome measure.

Conditions
Cystic Fibrosis
Being tested
Ataluren (PTC124®), Placebo
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ataluren (PTC124®)Drug

    Oral Ataluren TID

  • PlaceboDrug

    Oral Placebo TID

Study groups in NCT02139306
Study groupRoleWhat they receive
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.
Receives: Drug: Ataluren (PTC124®)
PlaceboPlacebo comparatorParticipants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From Baseline to Week 48

Secondary outcomes (9)

  1. 48-week Rate of Pulmonary Exacerbations

    Pulmonary exacerbations were assessed using expanded Fuchs criteria. The expanded Fuchs exacerbation is defined as the presence of at least 4 of 12 Fuchs' signs and symptoms requiring treatment with any form of antibiotic treatment (inhaled, oral, or intravenous). Fuchs' signs and symptoms included increased cough; change in sputum volume, color, or consistency; new or increased hemoptysis; increased dyspnea during moderate or mild exertion, or at rest; sinus pain or tenderness; change in sinus discharge; malaise, fatigue, or lethargy; anorexia or weight loss; temperature above 38 degrees Celsius; change in findings on chest examination; relative 10% decrease in ppFEV1, and chest radiography results consistent with pulmonary infection. The 48-week rate was calculated as: 48-week rate = total number of events /treatment duration by week*48.

    Measured: Week 48

  2. Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48

    The teen/adult CFQ-R was used for this study. It was developed specifically for participants with cystic fibrosis. It is a disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being, and symptoms. The respiratory domain assessed respiratory symptoms like coughing, congestion, wheezing etc. Scaling of each item is done via 4-point Likert scales. Scores for each item are summed up to generate a domain score. Scores ranges from 0 to 100, with higher scores indicating better health and lower scores indicating worse health.

    Measured: Baseline (Day 1) and Week 48

  3. Change From Baseline in Body Mass Index (BMI) at Week 48

    Malnutrition is common in participants with cystic fibrosis. The BMI is an important clinical measure of nutritional status.

    Measured: Baseline (Day 1) and Week 48

  4. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

    An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from first dose of study drug to 4 weeks after last dose of study drug. An SAE is an untoward medical occurrence or effect associated with the use of a study drug at any dose, regardless of whether it is considered to be related to the study drug, which results in one of the following: death; inpatient hospitalization or prolongation of existing hospitalization; life threatening adverse event; persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; any other medically important event; or a pregnancy resulting in spontaneous abortion, stillbirth, neonatal death, or congenital anomaly.

    Measured: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

  5. Number of Participants With TEAEs by Severity and Relationship to Study Drugs

    The relationship of TEAEs to the study drugs were assessed as: probable related, possibly related, unlikely related, and unrelated. The severity of TEAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal).

    Measured: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

  6. Number of Participants With SAEs by Severity and Relationship to Study Drugs

    The relationship of SAEs to the study drugs were assessed as: probable related, possibly related, unlikely related, and unrelated. The severity of SAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal).

    Measured: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

  7. Number of Participants With Abnormal Vital Signs Reported as TEAEs

    Vital signs included systolic and diastolic blood pressure, pulse rate, pulse oximetry, and body temperature. Participants with abnormal vital signs who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.

    Measured: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

  8. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

    Clinical laboratory tests included haematology, biochemistry, and urinalysis. Participants with abnormal laboratory parameters who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.

    Measured: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

  9. Number of Participants With Abnormal Electrocardiogram Reported as TEAEs

    Participants with abnormal electrocardiogram who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.

    Measured: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2014 (estimated)
  2. Study startAug 2014
  3. Primary completionNov 2016
  4. Study completionNov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
279 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02139306
Sponsor's protocol ID
PTC124-GD-021-CF
Other IDs
2013-004581-34
Status last verified
May 2020
First submitted
13 May 2014
Last updated
14 May 2020
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 36866921

  • VanDevanter 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.

    PubMed 32682670

  • Konstan 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.

    PubMed 31983658

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ataluren (PTC124®) in people with Cystic Fibrosis, run by PTC Therapeutics at 88 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 88 sites in United States, Germany, United Kingdom, Italy, Spain and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48 (time frame: From Baseline to Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02139306, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2020.

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