Cystic Fibrosis
Conditions
Brief summary
This study will evaluate the efficacy of ivacaftor treatment in subjects with CF 6 years of age and older who have a 3849 + 10KB C→T or D1152H CFTR mutation.
Interventions
DRUGIvacaftor
IVA 150 mg tablet.
DRUGPlacebo
Placebo matched to IVA tablet.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CF based on protocol-specified clinical features and at least one of the following: increased sweat chloride level, identification of 2 CF causing mutations, or demonstration of abnormal nasal epithelial ion transport. * A 3849 + 10KB C→T or D1152H mutation on at least 1 CFTR allele. * FEV1 ≥40% of predicted and ≤105% of predicted at screening.
Exclusion criteria
* A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation. * History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. * Ongoing or prior participation in an investigational drug study within 30 days before the Screening Visit. * Protocol-specified abnormal laboratory values at the Screening Visit * For subjects \<18 years of age at the Screening Visit, evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination (OE) at the Screening Visit. * Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1. * Pregnant, breastfeeding, or planning to become pregnant during the study. * Sexually active subjects of reproductive potential must be willing to use appropriate contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lung Clearance Index 2.5 (LCI2.5) | From baseline through 8 weeks | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. |
Countries
Israel
Participant flow
Pre-assignment details
This study was conducted in participants with cystic fibrosis (CF).
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: First IVA Then Placebo Participants received IVA 150 mg q12h for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | 19 |
| Sequence 2: First Placebo Then IVA Participants received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA 150 mg q12h for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | 19 |
| Total | 38 |
Baseline characteristics
| Characteristic | Sequence 1: First IVA Then Placebo | Sequence 2: First Placebo Then IVA | Total |
|---|---|---|---|
| Age, Continuous | 32.6 years STANDARD_DEVIATION 15.3 | 32.1 years STANDARD_DEVIATION 15.6 | 32.3 years STANDARD_DEVIATION 15.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 19 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Lung Clearance Index 2.5 (LCI2.5) | 12.74 lung clearance index STANDARD_DEVIATION 4.04 | 13.19 lung clearance index STANDARD_DEVIATION 5.45 | 12.96 lung clearance index STANDARD_DEVIATION 4.74 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 19 Participants | 38 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 38 |
| other Total, other adverse events | 19 / 38 | 12 / 38 |
| serious Total, serious adverse events | 2 / 38 | 1 / 38 |
Outcome results
Primary
Change in Lung Clearance Index 2.5 (LCI2.5)
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time frame: From baseline through 8 weeks
Population: The Full Analysis Set (FAS) included all randomized subjects who carried the intended CFTR allele mutation and received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Lung Clearance Index 2.5 (LCI2.5) | 0.20 lung clearance index | Standard Error 0.19 |
| Ivacaftor | Change in Lung Clearance Index 2.5 (LCI2.5) | -0.46 lung clearance index | Standard Error 0.19 |
95% CI: [-1.1, -0.21]