Trial Outcomes & Findings for Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF) (NCT NCT02139306)

Last Updated: 2020-05-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

279 participants

Primary outcome timeframe

From Baseline to Week 48

Results posted on

2020-05-14

Participant Flow

This study was conducted from 15 August 2014 to 02 November 2016.

Participant milestones

Participant milestones
Measure	Ataluren Participants 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 Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Overall Study STARTED	140	139
Overall Study COMPLETED	127	125
Overall Study NOT COMPLETED	13	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Ataluren Participants 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 Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Overall Study Withdrawal by Subject	4	6
Overall Study Adverse Event	3	4
Overall Study Physician Decision	0	1
Overall Study Other Unspecified	2	3
Overall Study Protocol Violation	4	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ataluren n=140 Participants Participants 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 n=139 Participants Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.	Total n=279 Participants Total of all reporting groups
Age, Continuous	22.0 years STANDARD_DEVIATION 11.0 • n=5 Participants	22.0 years STANDARD_DEVIATION 10.44 • n=7 Participants	22.0 years STANDARD_DEVIATION 10.70 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	74 Participants n=7 Participants	133 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	65 Participants n=7 Participants	146 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 48

Population: The intent-to-treat (ITT) population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Ataluren n=138 Participants Participants 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 n=136 Participants Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48	-1.396 Percentage of predicted FEV1 Interval -2.7735 to -0.018	-1.992 Percentage of predicted FEV1 Interval -3.3271 to -0.6576

SECONDARY outcome

Timeframe: Week 48

Population: The ITT population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

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.

Outcome measures

Outcome measures
Measure	Ataluren n=138 Participants Participants 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 n=136 Participants Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
48-week Rate of Pulmonary Exacerbations	0.950 number of exacerbations per 48 weeks Standard Deviation 1.4038	1.127 number of exacerbations per 48 weeks Standard Deviation 2.5241

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: The ITT population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

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.

Outcome measures

Outcome measures
Measure	Ataluren n=138 Participants Participants 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 n=136 Participants Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48	-0.760 units on a scale Interval -3.4566 to 1.9364	-1.032 units on a scale Interval -3.7368 to 1.6728

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: The ITT population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

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

Outcome measures

Outcome measures
Measure	Ataluren n=138 Participants Participants 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 n=136 Participants Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Change From Baseline in Body Mass Index (BMI) at Week 48	0.296 kilogram per meter square (kg/m^2) Interval 0.1126 to 0.4789	0.361 kilogram per meter square (kg/m^2) Interval 0.1759 to 0.5455

SECONDARY outcome

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