Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating Mutation (NCT NCT02742519)
NCT ID: NCT02742519
Last Updated: 2018-11-19
Results Overview
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
14 participants
Primary outcome timeframe
Baseline Through Week 8 for each treatment period, Up to 24 Weeks
Results posted on
2018-11-19
Participant Flow
Study consisted of 2 parts: Part 1- Double Blind (DB) Crossover Treatment Period and Part 2- Open Label (OL) Period.
Participant milestones
| Measure |
Part 1 Sequence 1: Ivacaftor First, Then Placebo
Ivacaftor administered every 12 hours for 8 weeks in treatment period 1 followed by placebo matched to Ivacaftor administered every 12 hours for 8 weeks in treatment period 2. Washout period of 8 weeks occurred between treatment period 1 and treatment period 2. For ivacaftor, the dose was either 50 milligram (mg) or 75 mg, as determined by the participant's body weight on Day 1.
|
Part 1 Sequence 2: Placebo First, Then Ivacaftor
Placebo matched to Ivacaftor administered every 12 hours for 8 weeks in treatment period 1 followed by Ivacaftor administered every 12 hours for 8 weeks in treatment period 2. Washout period of 8 weeks occurred between treatment period 1 and treatment period 2. For ivacaftor, the dose was either 50 mg or 75 mg, as determined by the participant's body weight on Day 1.
|
Part 2: Ivacaftor
Ivacaftor 50 mg, 75 mg or 150 mg, as determined by the participant's body weight at the beginning of Part 2, administered every 12 hours for up to 32 weeks in open label period.
|
|---|---|---|---|
|
Part 1 Treatment Period 1 (8 Weeks)
STARTED
|
8
|
6
|
0
|
|
Part 1 Treatment Period 1 (8 Weeks)
COMPLETED
|
8
|
6
|
0
|
|
Part 1 Treatment Period 1 (8 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
|
Part 1 Treatment Period 2 (8 Weeks)
STARTED
|
8
|
6
|
0
|
|
Part 1 Treatment Period 2 (8 Weeks)
COMPLETED
|
7
|
5
|
0
|
|
Part 1 Treatment Period 2 (8 Weeks)
NOT COMPLETED
|
1
|
1
|
0
|
|
Part 2 Open Label Period (32 Weeks)
STARTED
|
0
|
0
|
10
|
|
Part 2 Open Label Period (32 Weeks)
COMPLETED
|
0
|
0
|
0
|
|
Part 2 Open Label Period (32 Weeks)
NOT COMPLETED
|
0
|
0
|
10
|
Reasons for withdrawal
| Measure |
Part 1 Sequence 1: Ivacaftor First, Then Placebo
Ivacaftor administered every 12 hours for 8 weeks in treatment period 1 followed by placebo matched to Ivacaftor administered every 12 hours for 8 weeks in treatment period 2. Washout period of 8 weeks occurred between treatment period 1 and treatment period 2. For ivacaftor, the dose was either 50 milligram (mg) or 75 mg, as determined by the participant's body weight on Day 1.
|
Part 1 Sequence 2: Placebo First, Then Ivacaftor
Placebo matched to Ivacaftor administered every 12 hours for 8 weeks in treatment period 1 followed by Ivacaftor administered every 12 hours for 8 weeks in treatment period 2. Washout period of 8 weeks occurred between treatment period 1 and treatment period 2. For ivacaftor, the dose was either 50 mg or 75 mg, as determined by the participant's body weight on Day 1.
|
Part 2: Ivacaftor
Ivacaftor 50 mg, 75 mg or 150 mg, as determined by the participant's body weight at the beginning of Part 2, administered every 12 hours for up to 32 weeks in open label period.
|
|---|---|---|---|
|
Part 1 Treatment Period 2 (8 Weeks)
Availability of commercial drug
|
1
|
1
|
0
|
|
Part 2 Open Label Period (32 Weeks)
Availability of commercial drug
|
0
|
0
|
9
|
|
Part 2 Open Label Period (32 Weeks)
Other
|
0
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating Mutation
Baseline characteristics by cohort
| Measure |
Part 1 Sequence 1: Ivacaftor First, Then Placebo
n=8 Participants
Ivacaftor administered every 12 hours for 8 weeks in treatment period 1 followed by placebo matched to Ivacaftor administered every 12 hours for 8 weeks in treatment period 2. Washout period of 8 weeks occurred between treatment period 1 and treatment period 2. For ivacaftor, the dose was either 50 milligram (mg) or 75 mg, as determined by the participant's body weight on Day 1.
|
Part 1 Sequence 2: Placebo First, Then Ivacaftor
n=6 Participants
Placebo matched to Ivacaftor administered every 12 hours for 8 weeks in treatment period 1 followed by Ivacaftor administered every 12 hours for 8 weeks in treatment period 2. Washout period of 8 weeks occurred between treatment period 1 and treatment period 2. For ivacaftor, the dose was either 50 mg or 75 mg, as determined by the participant's body weight on Day 1.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
3.6 years
STANDARD_DEVIATION 0.7 • n=5 Participants
|
4.2 years
STANDARD_DEVIATION 1.0 • n=7 Participants
|
3.9 years
STANDARD_DEVIATION 0.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline Through Week 8 for each treatment period, Up to 24 WeeksPopulation: Full Analysis Set (FAS) was used which included all randomized participants who had mutation on at least 1 allele, received at least 1 dose of study drug (Ivacaftor or placebo) and had at least 1 post-baseline assessment.
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Outcome measures
| Measure |
Placebo (Crossover Part)
n=13 Participants
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=13 Participants
Ivacaftor administered as determined by the participant's body weight on Day 1 orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
Ivacaftor administered as determined by the participant's body weight in the beginning of Part 2 orally every 12 hours in for up to 34 weeks in open label period.
|
|---|---|---|---|
|
Absolute Change From Baseline in Lung Clearance Index (LCI2.5) Through 8 Weeks of Treatment (Average of Week 4 and Week 8 LCI2.5)
|
-0.07 Lung clearance index
Standard Deviation 0.93
|
-0.53 Lung clearance index
Standard Deviation 1.23
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 8 of each treatment period, Up to 24 WeeksPopulation: FAS was used which included all randomized participants who had mutation on at least 1 allele, received at least 1 dose of study drug (Ivacaftor or placebo) and had at least 1 post-baseline assessment. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome measure.
Serum samples were collected for evaluation of change in immunoreactive trypsinogen levels at Week 8.
Outcome measures
| Measure |
Placebo (Crossover Part)
n=3 Participants
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=4 Participants
Ivacaftor administered as determined by the participant's body weight on Day 1 orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
Ivacaftor administered as determined by the participant's body weight in the beginning of Part 2 orally every 12 hours in for up to 34 weeks in open label period.
|
|---|---|---|---|
|
Absolute Change From Baseline in Immunoreactive Trypsinogen Levels at Week 8
|
-9.3 Nanogram per milliliter (ng/mL)
Standard Deviation 18.4
|
-15.5 Nanogram per milliliter (ng/mL)
Standard Deviation 6.5
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 8 of each treatment period, Up to 24 WeeksPopulation: FAS was used which included all randomized participants who had mutation on at least 1 allele, received at least 1 dose of study drug (Ivacaftor or placebo) and had at least 1 post-baseline assessment. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome measure.
Fecal elastase-1 was used clinically to diagnose pancreatic exocrine insufficiency in participants with cystic fibrosis.
Outcome measures
| Measure |
Placebo (Crossover Part)
n=11 Participants
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=10 Participants
Ivacaftor administered as determined by the participant's body weight on Day 1 orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
Ivacaftor administered as determined by the participant's body weight in the beginning of Part 2 orally every 12 hours in for up to 34 weeks in open label period.
|
|---|---|---|---|
|
Absolute Change From Baseline in Fecal Elastase-1 Levels at Week 8
|
-17.0 microgram per gram (mcg/g)
Standard Deviation 55.4
|
23.1 microgram per gram (mcg/g)
Standard Deviation 37.9
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 8 of each treatment period, Up to 24 WeeksPopulation: FAS was used which included all randomized participants who had mutation on at least 1 allele, received at least 1 dose of study drug (Ivacaftor or placebo) and had at least 1 post-baseline assessment.
Outcome measures
| Measure |
Placebo (Crossover Part)
n=13 Participants
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=13 Participants
Ivacaftor administered as determined by the participant's body weight on Day 1 orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
Ivacaftor administered as determined by the participant's body weight in the beginning of Part 2 orally every 12 hours in for up to 34 weeks in open label period.
|
|---|---|---|---|
|
Absolute Change From Baseline in Weight at Week 8
|
0.9 Kilogram (kg)
Standard Deviation 1.0
|
1.1 Kilogram (kg)
Standard Deviation 0.9
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 8 of each treatment period, Up to 24 WeeksPopulation: FAS was used which included all randomized participants who had mutation on at least 1 allele, received at least 1 dose of study drug (Ivacaftor or placebo) and had at least 1 post-baseline assessment.
BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Outcome measures
| Measure |
Placebo (Crossover Part)
n=13 Participants
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=13 Participants
Ivacaftor administered as determined by the participant's body weight on Day 1 orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
Ivacaftor administered as determined by the participant's body weight in the beginning of Part 2 orally every 12 hours in for up to 34 weeks in open label period.
|
|---|---|---|---|
|
Absolute Change From Baseline in Body Mass Index (BMI) at Week 8
|
0.13 Kilogram per meter square (kg/m^2)
Standard Deviation 0.79
|
0.32 Kilogram per meter square (kg/m^2)
Standard Deviation 0.59
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Month 15Population: The Safety Set was used which included all participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Placebo (Crossover Part)
n=13 Participants
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=13 Participants
Ivacaftor administered as determined by the participant's body weight on Day 1 orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
n=10 Participants
Ivacaftor administered as determined by the participant's body weight in the beginning of Part 2 orally every 12 hours in for up to 34 weeks in open label period.
|
|---|---|---|---|
|
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with any AEs
|
11 Participants
|
11 Participants
|
6 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Placebo (Crossover Part)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Ivacaftor (Crossover Part)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Ivacaftor (Open Label Part)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo (Crossover Part)
n=13 participants at risk
Placebo matched to Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Crossover Part)
n=13 participants at risk
Ivacaftor administered orally every 12 hours for 8 weeks in treatment period 1 or treatment period 2.
|
Ivacaftor (Open Label Part)
n=10 participants at risk
Ivacaftor administered orally every 12 hours in open label period.
|
|---|---|---|---|
|
Investigations
Haemophilus test positive
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
10.0%
1/10 • Baseline up to Month 15
|
|
Investigations
Streptococcus test positive
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
10.0%
1/10 • Baseline up to Month 15
|
|
Investigations
Bacterial test positive
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Investigations
Pseudomonas test positive
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Skin and subcutaneous tissue disorders
Cough
|
23.1%
3/13 • Baseline up to Month 15
|
15.4%
2/13 • Baseline up to Month 15
|
40.0%
4/10 • Baseline up to Month 15
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
23.1%
3/13 • Baseline up to Month 15
|
23.1%
3/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.7%
1/13 • Baseline up to Month 15
|
15.4%
2/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
10.0%
1/10 • Baseline up to Month 15
|
|
Nervous system disorders
Headache
|
23.1%
3/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Nervous system disorders
Lethargy
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
General disorders
Pyrexia
|
7.7%
1/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13 • Baseline up to Month 15
|
23.1%
3/13 • Baseline up to Month 15
|
30.0%
3/10 • Baseline up to Month 15
|
|
Gastrointestinal disorders
Constipation
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
23.1%
3/13 • Baseline up to Month 15
|
23.1%
3/13 • Baseline up to Month 15
|
30.0%
3/10 • Baseline up to Month 15
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
1/13 • Baseline up to Month 15
|
23.1%
3/13 • Baseline up to Month 15
|
10.0%
1/10 • Baseline up to Month 15
|
|
Infections and infestations
Viral upper respiratory tract infection
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
10.0%
1/10 • Baseline up to Month 15
|
|
Infections and infestations
Bacterial disease carrier
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Infections and infestations
Otitis media
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/13 • Baseline up to Month 15
|
7.7%
1/13 • Baseline up to Month 15
|
0.00%
0/10 • Baseline up to Month 15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
- Publication restrictions are in place
Restriction type: OTHER