Cystic Fibrosis
Conditions
Brief summary
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study that will evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation.
Interventions
DRUGLUM/IVA
LUM 400 mg/IVA 250 mg every 12 hours (q12h)
DRUGPlacebo
No Active Drug
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
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female with confirmed diagnosis of CF * All subjects must have an A455E mutation on at least 1 CFTR allele; no more than 10 subjects may have an F508del mutation on 1 CFTR allele. * Forced expiratory volume in one second (FEV1) ≥30% of predicted and ≤90% of predicted at the Screening Visit, based on the Global Lung Function Initiative (GLI)-2012 multi ethnic all-age reference equations. * Stable CF disease as judged by the investigator. * Willing to remain on a stable medication regimen for CF from 4 weeks before Day 1 through the Follow up Visit.
Exclusion criteria
* History of any comorbidity reviewed at the Screening Visit 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. * A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation on at least one CFTR allele. * Pregnant or breastfeeding. * Any abnormal laboratory values at the Screening Visit. * History of cataract/lens opacity, or evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination at the Screening Visit. * Use of strong inhibitors or strong inducers of CYP3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1 * Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8 | Study Baseline, Through Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
Countries
Netherlands
Participant flow
Recruitment details
A total of 20 subjects were enrolled in this cross-over study.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: First LUM/IVA, Then Placebo Participants received LUM 400 mg/IVA 250 mg fixed dose combination tablet orally q12h for 8 weeks in treatment period 1 followed by placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period. | 10 |
| Sequence 2: First Placebo, Then LUM/IVA Participants received placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 1 followed by LUM 400 mg/IVA 250 mg fixed dose combination tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period (8 Weeks) | Adverse Event | 2 | 1 |
Baseline characteristics
| Characteristic | Sequence 2: First Placebo, Then LUM/IVA | Total | Sequence 1: First LUM/IVA, Then Placebo |
|---|---|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 11.8 | 38.0 years STANDARD_DEVIATION 13.6 | 41.2 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 20 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 19 |
| other Total, other adverse events | 13 / 18 | 15 / 19 |
| serious Total, serious adverse events | 0 / 18 | 0 / 19 |
Outcome results
Primary
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: Study Baseline, Through Week 8
Population: Full Analysis set included as all randomized participants who had at least 1 A455E mutation and received at least 1 dose of study drug. Here Overall number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8 | 2.6 Percentage of predicted FEV1 |
| LUM/IVA | Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8 | 2.7 Percentage of predicted FEV1 |
p-value: 0.927795% CI: [-2.5, 2.7]Mixed Model Repeated Measure (MMRM)