Cystic Fibrosis
Conditions
Brief summary
This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in participants with cystic fibrosis (CF) who are \<24 months of age at treatment initiation and have an approved Ivacaftor-Responsive mutation.
Interventions
DRUGIVA
Granules for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
Ivacaftor Arm: Participants From Study 124 (NCT02725567 ) Part B: * Participants transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B. * As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the informed consent form (ICF). Ivacaftor Arm: Participants Not From Study 124 Part B: * Confirmed diagnosis of CF, or 2 CF-causing mutations. * An ivacaftor- responsive CFTR mutation on at least 1 allele. Participants will be eligible in countries/regions where ivacaftor is approved for use in participants 2 years of age and older. * As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF. Observational Arm: * Received ivacaftor treatment in Study 124 Part B and elected not to enroll or ineligible to enroll in the ivacaftor arm of Study 126.
Exclusion criteria
Ivacaftor Arm: Participants From Study 124 Part B: * History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant. * Participants receiving commercially available ivacaftor treatment Ivacaftor Arm: Participants Not From Study 124 Part B: * History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant * An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 * Abnormal liver function at screening * Hemoglobin \<9.5 g/dL at screening * History of solid organ or hematological transplantation * Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1 Observational Arm: * Receiving ivacaftor treatment Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Day 1 up to Week 120 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Sweat Chloride | From Baseline at Week 96 | Sweat samples were collected using an approved collection device. |
Countries
Australia, Canada, Germany, Ireland, United Kingdom, United States
Participant flow
Recruitment details
This study was planned to include 2 arms: an ivacaftor (IVA) arm (open-label, 96-week treatment period) and an observational arm. However, there were no participants enrolled in the observational arm. A total of 86 participants enrolled in the Ivacaftor arm.
Pre-assignment details
Rollover participants (who completed parent study VX15-770-124 \[NCT02725567\] Part B or Part A/B) and IVA-naïve participants (who participated in study VX15-770-124 Part A only or who did not participate in VX15-770-124 and were less than (\<) 24 months of age at the Day 1 of current study \[VX15-770-126\]) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Ivacaftor Treatment Participants \<24 months of age and weighing 5 \<7 kg received 25 mg IVA q12h, 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants \>=24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing \>=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. | 86 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Commercial Drug is Available for Participants | 20 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other | 2 |
| Overall Study | Withdrawal of Consent (not due to AE) | 3 |
Baseline characteristics
| Characteristic | Ivacaftor Treatment |
|---|---|
| Age, Continuous | 10.2 months STANDARD_DEVIATION 5.19 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants |
| Race/Ethnicity, Customized Not collected per local regulations | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 79 Participants |
| Race/Ethnicity, Customized White | 82 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 86 |
| other Total, other adverse events | 83 / 86 |
| serious Total, serious adverse events | 21 / 86 |
Outcome results
Primary
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Day 1 up to Week 120
Population: Safety Set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ivacaftor Treatment | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 85 Participants |
| Ivacaftor Treatment | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with SAEs | 21 Participants |
Secondary
Absolute Change in Sweat Chloride
Sweat samples were collected using an approved collection device.
Time frame: From Baseline at Week 96
Population: The Full Analysis Set (FAS) included all participants who were enrolled and have at least 1 post baseline efficacy assessment in this study. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ivacaftor Treatment | Absolute Change in Sweat Chloride | -55.3 millimole per liter (mmol/L) | Standard Deviation 25 |