A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
- Registration Number
- NCT03525574
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
The study evaluates the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 507
- Completed study drug treatment in a parent study i.e.VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548); or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.
- History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator.
- Current participation in an investigational drug trial (other than a parent study)
Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ELX/TEZ/IVA IVA Treatment Period: Participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hrs (q12h) in the treatment period for 192 weeks. Extension Period: Participants from certain countries participated in extension period and continued to receive ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the extension period for 48 weeks. ELX/TEZ/IVA ELX/TEZ/IVA Treatment Period: Participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hrs (q12h) in the treatment period for 192 weeks. Extension Period: Participants from certain countries participated in extension period and continued to receive ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the extension period for 48 weeks.
- Primary Outcome Measures
Name Time Method Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From Day 1 up to Week 196
- Secondary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set From Baseline at Week 192 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in BMI Z-score for 103/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kg divided by height in m\^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set From Baseline at Week 192 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time to First PEx for 103/105 Efficacy Set From Baseline at Week 192 Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in BMI Z-score for 102/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kg divided by height in m\^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set From Baseline at Week 192 Sweat samples were collected using an approved collection device. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set From Baseline at Week 192 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set From Baseline at Week 192 Sweat samples were collected using an approved collection device. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set From Baseline at Week 192 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time to First PEx for 102/105 Efficacy Set From Baseline at Week 192 Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Body Weight for 102/105 Efficacy Set From Baseline at Week 192 This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set From Baseline at Week 192 The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.
Absolute Change in Body Weight for 103/105 Efficacy Set From Baseline at Week 192 This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set From Baseline at Week 192 The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Trial Locations
- Locations (110)
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Miller Children's Hospital / Long Beach Memorial
🇺🇸Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Kaiser Permanente
🇺🇸Oakland, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
UCSF Gateway Medical Center
🇺🇸San Francisco, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
University of Florida, Shands Hospital
🇺🇸Gainesville, Florida, United States
Scroll for more (100 remaining)Banner University of Arizona Medical Center🇺🇸Tucson, Arizona, United States