Cystic Fibrosis
Conditions
Brief summary
This study will evaluate the efficacy and safety of CTP-656 in patients with cystic fibrosis (CF) who have a cystic fibrosis transmembrane conductance regulator (CFTR) gating mutation.
Detailed description
This is a randomized, parallel-group, double-blind, placebo controlled multicenter study to evaluate the safety and efficacy of CTP-656 in CF patients with CFTR gating mutations, compared to Kalydeco, for a total of 28 days. Subjects will be randomized to receive either double-blind CTP-656 or placebo, or open-label Kalydeco.
Interventions
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Has a confirmed diagnosis of CF with at least one allele of the following CFTR gating mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, and S549R. * Has been stable on Kalydeco therapy for at least 3 months prior to screening * Has FEV1 ≥ 60% of predicted normal for age, sex, and height at screening and baseline (Day 1) assessments * Weighs at least 40 kg at screening * Patients of either gender and women of childbearing potential must be willing to use a medically highly effective form of birth control during the treatment period and 30 days after the last dose of study treatment.
Exclusion criteria
* Acute upper respiratory infection or lower respiratory infection, pulmonary exacerbation, or changes in therapy within 4 weeks of study treatment * Uncontrolled type 2 diabetes, or uncontrolled CF-related diabetes * History of hepatitis C or chronic active hepatitis B infection * History of pulmonary tuberculosis, non-tuberculosis mycobacterial infections or allergic bronchopulmonary aspergillosis (ABPA) treated during screening or within 2 years prior to screening * Colonization with B. cenocepacia, B. dolosa, B. multivorans, and/or M. abcessus within 2 years prior to Screening * Abnormal liver function * History of abnormal renal function * History of prolonged QTcF \> 450 msec for males or QTcF \> 470 msec for females * History of solid organ or hematological transplantation * Using any inhibitor or inducer of cytochrome P450/3A during the study or within 30 days of screening * Women who are pregnant or lactating, or have plans to become pregnant during the study or within 1 month following the last dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Sweat Chloride at Day 28 | From baseline at Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28 | From baseline at Day 28 |
| Change From Baseline in Cystic Fibrosis Questionnaire-Respiratory Domain (CFQ-R) at Day 28 | From baseline at Day 28 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VX-561 20 mg Participants received VX-561 20 mg orally once daily for 28 days. | 2 |
| VX-561 100 mg Participants received VX-561 100 mg orally once daily for 28 days. | 2 |
| VX-561 150 mg Participants received VX-561 150 mg orally once daily for 28 days. | 2 |
| Placebo Participants received placebo matched to VX-561 orally once daily for 28 days. | 2 |
| Ivacaftor Participants received Ivacaftor 150 mg orally every 12 hours for 28 days. | 3 |
| Total | 11 |
Baseline characteristics
| Characteristic | VX-561 20 mg | Total | Ivacaftor | Placebo | VX-561 150 mg | VX-561 100 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 24.0 years STANDARD_DEVIATION 1.41 | 22.2 years STANDARD_DEVIATION 4 | 19.7 years STANDARD_DEVIATION 0.58 | 29.0 years STANDARD_DEVIATION 2.83 | 19.5 years STANDARD_DEVIATION 2.12 | 20.0 years STANDARD_DEVIATION 1.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 10 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 11 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sweat Chloride | 59.25 millimole per liter (mmol/L) STANDARD_DEVIATION 16.617 | 62.15 millimole per liter (mmol/L) STANDARD_DEVIATION 27.355 | 71.25 millimole per liter (mmol/L) STANDARD_DEVIATION 37.83 | 36.50 millimole per liter (mmol/L) STANDARD_DEVIATION 29.698 | 61.50 millimole per liter (mmol/L) STANDARD_DEVIATION 32.527 | 82.25 millimole per liter (mmol/L) STANDARD_DEVIATION 27.931 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 1 / 2 | 2 / 2 | 1 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 3 |
Outcome results
Primary
Change From Baseline in Sweat Chloride at Day 28
Time frame: From baseline at Day 28
Population: As pre-specified in SAP section 4.13 (Changes in Conduct or Planned Analyses), due to the limited number of participants being enrolled in the study, model-based analyses and summary statistics plan were not performed. Therefore, no efficacy summary is provided for this outcome measure.
Secondary
Change From Baseline in Cystic Fibrosis Questionnaire-Respiratory Domain (CFQ-R) at Day 28
Time frame: From baseline at Day 28
Population: As pre-specified in SAP section 4.13 (Changes in Conduct or Planned Analyses), due to the limited number of participants being enrolled in the study, all model-based analyses and summary statistics are no longer applicable and are therefore removed from analysis plan. Therefore no efficacy summary is available for this outcome measure.
Secondary
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
Time frame: From baseline at Day 28
Population: As pre-specified in SAP section 4.13 (Changes in Conduct or Planned Analyses), due to the limited number of participants being enrolled in the study, all model-based analyses and summary statistics are no longer applicable and are therefore removed from analysis plan. Therefore no efficacy summary is available for this outcome measure.