Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

• ELX/TEZ/IVA (Drug), also known as VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor: Fixed-dose combination (FDC) tablet for oral administration.
• IVA (Drug), also known as VX-770, ivacaftor: Tablet for oral administration.

Primary outcomes

• Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From Baseline up to Week 100]

Secondary outcomes

• Part A: Absolute Change From Parent Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline at Week 96]: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
• Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl) [From Baseline at Week 96]: Sweat samples were collected using an approved collection device.
• Part A: Absolute Change From Parent Study Baseline in Body Mass Index (BMI) [From Baseline at Week 96]: BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
• Part A: Absolute Change From Parent Study Baseline in BMI Z-score [From Baseline at Week 96]: BMI was defined as weight in kilogram (kg) divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
• Part A: Absolute Change From Parent Study Baseline in Body Weight [From Baseline at Week 96]
• Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [From Baseline at Week 96]: 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.

Sex: All, ages: 12 Years to any

Key Inclusion Criteria:

* Completed study drug treatment in parent study (VX18-445-104); or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study

Key Exclusion Criteria:

* History of study drug intolerance in parent study

Other protocol defined Inclusion/Exclusion criteria may apply.

Participant flow

Outcome results

• Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Primary), Count of participants, Participants: Part A: ELX/TEZ/IVA 241
• Part A: Absolute Change From Parent Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (Secondary), Least squares mean, percentage points: ELX/TEZ/IVA 4.1 (2.5 to 5.7)
• Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl) (Secondary), Least squares mean, millimole per liter (mmol/L): ELX/TEZ/IVA -23.0 (-25.8 to -20.1)
• Part A: Absolute Change From Parent Study Baseline in Body Mass Index (BMI) (Secondary), Least squares mean, kg/m^2: ELX/TEZ/IVA 1.15 (0.84 to 1.45)
• Part A: Absolute Change From Parent Study Baseline in BMI Z-score (Secondary), Least squares mean, z-score: ELX/TEZ/IVA 0.11 (-0.17 to 0.40)
• Part A: Absolute Change From Parent Study Baseline in Body Weight (Secondary), Least squares mean, Kilogram (Kg): ELX/TEZ/IVA 3.6 (2.7 to 4.6)
• Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score (Secondary), Least squares mean, units on a scale: ELX/TEZ/IVA 7.2 (4.1 to 10.4)

Adverse events

Time frame: Day 1 through Safety follow-up (up to Week 100 for Part A and up to Week 52 for Part B)

Serious adverse events by term

Other adverse events by term

• Results publication: Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4. PMID 37983082
• Results publication: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. PMID 33331662

• Study Protocol (PDF, 2020-07-29)
• Statistical Analysis Plan (PDF, 2022-02-02)

NIH grants: 2019