Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age.

Official Title
-----------------
A Phase 3 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 2 Through 5 Years of Age

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: ELX/TEZ/IVA
* Drug: IVA


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Homozygous for the F508del mutation or heterozygous for F508del and a minimal function (MF) mutation (F/F or F/MF genotypes) Key Exclusion Criteria: Clinically significant cirrhosis with or without portal hypertension Lung infection with organisms associated with a more rapid decline in pulmonary status Solid organ or hematological transplantation Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 5 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: ELX/TEZ/IVA<br>Participants weighing greater than or equal to (>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days. | Drug: ELX/TEZ/IVA<br>* Fixed dose combination granules for oral administration.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Granules for oral administration.<br>* Other names: ivacaftor;|
| Experimental: Part B: ELX/TEZ/IVA<br>Participants weighing (>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (>=)10 kg to less than (<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) in the treatment period for 24 weeks. | Drug: ELX/TEZ/IVA<br>* Fixed dose combination granules for oral administration.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Granules for oral administration.<br>* Other names: ivacaftor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites |  | From Day 1 through Day 15 | 
| Part A: 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 Day 43 | 
| Part B: 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 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites |  | From Day 1 through Week 16 | 
| Part B: Absolute Change in Sweat Chloride (SwCl) | Sweat samples were collected using an approved collection device. | From Baseline through Week 24 | 
| Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5) | The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry. | From Baseline through Week 24 |