Trial Outcomes & Findings for Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age (NCT NCT03691779)

NCT ID: NCT03691779

Last Updated: 2021-10-22

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

71 participants

Primary outcome timeframe

Part A: Day 15

Results posted on

2021-10-22

Participant Flow

The study was conducted in 2 parts, Part A and Part B. All results were planned to be analyzed and reported separately for Part A and Part B of the study.

This study was conducted in cystic fibrosis (CF) participants 6 through 11 years of age who were homozygous for F508del (F/F) genotype or heterozygous for F508del and a CF transmembrane conductance regulator gene (CFTR) minimal function mutation (F/MF) genotypes.

Participant milestones

Participant milestones
Measure	Part A: ELX/TEZ/IVA Participants in Part A 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.	Part B: ELX/TEZ/IVA Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Part A (15 Days) STARTED	16	0
Part A (15 Days) COMPLETED	16	0
Part A (15 Days) NOT COMPLETED	0	0
Part B (24 Weeks) STARTED	0	66
Part B (24 Weeks) COMPLETED	0	64
Part B (24 Weeks) NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: ELX/TEZ/IVA Participants in Part A 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.	Part B: ELX/TEZ/IVA Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Part B (24 Weeks) Adverse Event	0	1
Part B (24 Weeks) Withdrawal of consent (not due to AE)	0	1

Baseline Characteristics

Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ELX/TEZ/IVA n=71 Participants Part A: Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days. Part B: Participants in Part B weighing \<30 kg at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Age, Categorical Part A (15 Days) · <=18 years	16 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Categorical Part A (15 Days) · Between 18 and 65 years	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Categorical Part A (15 Days) · >=65 years	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Categorical Part B (24 Weeks) · <=18 years	66 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Categorical Part B (24 Weeks) · Between 18 and 65 years	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Categorical Part B (24 Weeks) · >=65 years	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part A (15 Days) · Female	11 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part A (15 Days) · Male	5 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part B (24 Weeks) · Female	39 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part B (24 Weeks) · Male	27 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (15 Days) · Hispanic or Latino	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (15 Days) · Not Hispanic or Latino	16 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (15 Days) · Unknown or Not Reported	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (24 Weeks) · Hispanic or Latino	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (24 Weeks) · Not Hispanic or Latino	58 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (24 Weeks) · Unknown or Not Reported	8 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · American Indian or Alaska Native	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · Asian	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · Native Hawaiian or Other Pacific Islander	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · Black or African American	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · White	16 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · More than one race	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (15 Days) · Unknown or Not Reported	0 Participants n=16 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · American Indian or Alaska Native	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · Asian	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · Native Hawaiian or Other Pacific Islander	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · Black or African American	0 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · White	57 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · More than one race	1 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (24 Weeks) · Unknown or Not Reported	8 Participants n=66 Participants • Data were planned to be analyzed and reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.

PRIMARY outcome

Timeframe: Part A: Day 15

Population: Pharmacokinetic (PK) set for Part A included all participants who have received at least 1 dose of study drug in Part A. Here, the "number analyzed" signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA ELX	6.13 microgram per milliliter (mcg/mL) Standard Deviation 1.52
Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA TEZ	6.93 microgram per milliliter (mcg/mL) Standard Deviation 1.96
Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA IVA	1.01 microgram per milliliter (mcg/mL) Standard Deviation 0.281

PRIMARY outcome

Timeframe: Part A: Day 15

Population: PK set (Part A). Here, the "number analyzed" signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA ELX	2.86 mcg/mL Standard Deviation 1.37
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA TEZ	1.06 mcg/mL Standard Deviation 0.366
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA IVA	0.297 mcg/mL Standard Deviation 0.173

PRIMARY outcome

Timeframe: Part A: Day 15

Population: PK set (Part A). This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA ELX	107 hourmicrogram per milliliter (hmcg/mL) Standard Deviation 28.7
Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA TEZ	58.4 hourmicrogram per milliliter (hmcg/mL) Standard Deviation 13.5
Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA IVA	8.12 hourmicrogram per milliliter (hmcg/mL) Standard Deviation 2.93

PRIMARY outcome

Timeframe: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)

Population: Safety set for Part B included all participants who received at least 1 dose of study drug in Part B. The safety and tolerability analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants With TEAEs	65 participants
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants With SAEs	1 participants

SECONDARY outcome

Timeframe: Part A: Day 15

Population: PK set (Part A). Here, the "number analyzed" signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) M23-ELX	1.60 mcg/mL Standard Deviation 0.657
Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) M1-TEZ	6.26 mcg/mL Standard Deviation 1.54
Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) M1-IVA	2.36 mcg/mL Standard Deviation 0.694

SECONDARY outcome

Timeframe: Part A: Day 15

Population: PK set (Part A). Here, the "number analyzed" signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) M23-ELX	1.30 mcg/mL Standard Deviation 0.585
Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) M1-TEZ	4.64 mcg/mL Standard Deviation 1.36
Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) M1-IVA	0.890 mcg/mL Standard Deviation 0.460

SECONDARY outcome

Timeframe: Part A: Day 15

Population: PK set (Part A). This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) M23-ELX	35.6 h*mcg/mL Standard Deviation 13.2
Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) M1-TEZ	133 h*mcg/mL Standard Deviation 30.4

SECONDARY outcome

Timeframe: Part A: Day 15

Population: PK set (Part A). Here "overall number of participants analyzed" signifies participants who were evaluable at the specified time points. This outcome measure was planned only for Part A arm.

The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=15 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)	9.41 h*mcg/mL Standard Deviation 3.06

SECONDARY outcome

Timeframe: Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)

Population: Safety set for Part A included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A arm.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=16 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs Participants With TEAEs	12 participants
Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs Participants With SAEs	0 participants

SECONDARY outcome

Timeframe: Part B: From Baseline Through Week 24

Population: Full analysis set (FAS) for Part B included all enrolled participants who carry the intended CFTR allele mutation and received at least 1 dose of study drug in Part B. The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	10.2 percentage points Interval 7.9 to 12.6

SECONDARY outcome

Timeframe: Part B: From Baseline Through Week 24

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Sweat Chloride (SwCl)	-60.9 millimole per liter (mmol/L) Interval -63.7 to -58.2

SECONDARY outcome

Timeframe: Part B: From Baseline Through Week 24

Population: FAS (Part B). The efficacy analysis for Part B was planned for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.

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.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score	7.0 units on a scale Interval 4.7 to 9.2

SECONDARY outcome

Timeframe: Part B: From Baseline at Week 24

BMI was defined as weight in kg divided by squared height in meters (m\^2).

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Body Mass Index (BMI)	1.02 kg/m^2 Interval 0.76 to 1.28

SECONDARY outcome

Timeframe: Part B: From Baseline at Week 24

BMI was defined as weight in 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.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in BMI For-Age Z-Score	0.37 z-score Interval 0.26 to 0.48

SECONDARY outcome

Timeframe: Part B: From Baseline at Week 24

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Weight	3.0 kg Interval 2.5 to 3.5

SECONDARY outcome

Timeframe: Part B: From Baseline at Week 24

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.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Weight-for-age Z-Score	0.25 z-score Interval 0.16 to 0.33

SECONDARY outcome

Timeframe: Part B: From Baseline at Week 24

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Height	2.3 centimeters (cm) Interval 1.9 to 2.7

SECONDARY outcome

Timeframe: Part B: From Baseline at Week 24

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Height-for-Age Z-Score	-0.05 z-score Interval -0.12 to 0.01

SECONDARY outcome

Timeframe: Part B: At Week 24

Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome.

The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=33 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale Liked it Very Much	16 participants
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale Liked it a Little	6 participants
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale Not sure	10 participants
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale Disliked it a Little	1 participants
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale Disliked it Very Much	0 participants

SECONDARY outcome

Timeframe: Part B: From Baseline Through Week 24

Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Number of Pulmonary Exacerbations Events	4 pulmonary exacerbations events

SECONDARY outcome

Timeframe: Part B: From Baseline Through Week 24

The total number of CF related hospitalization events across all participants were reported.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Number of CF Related Hospitalizations	0 hospitalizations

SECONDARY outcome

Timeframe: Part B: At Week 4

Population: The PK set for Part B included all participants who have received at least 1 dose of study drug in Part B. Here "number analyzed" signifies those participants who were evaluable at specified time points.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=65 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) ELX: Week 4 (<30 kg)	2.71 mcg/mL Standard Deviation 1.77
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) ELX: Week 4 (>=30 kg)	5.69 mcg/mL Standard Deviation 3.00
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) M23-ELX: Week 4 (<30 kg)	1.59 mcg/mL Standard Deviation 1.24
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) M23-ELX: Week 4 (>=30 kg)	4.41 mcg/mL Standard Deviation 2.97
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) TEZ: Week 4 (<30 kg)	1.43 mcg/mL Standard Deviation 1.19
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) TEZ: Week 4 (>=30 kg)	2.37 mcg/mL Standard Deviation 1.07
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) M1-TEZ: Week 4 (<30 kg)	5.57 mcg/mL Standard Deviation 1.78
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) M1-TEZ: Week 4 (>=30 kg)	8.12 mcg/mL Standard Deviation 1.88
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) IVA: Week 4 (<30 kg)	0.455 mcg/mL Standard Deviation 0.681
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) IVA: Week 4 (>=30 kg)	0.851 mcg/mL Standard Deviation 0.489
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) M1-IVA: Week 4 (<30 kg)	1.00 mcg/mL Standard Deviation 0.630
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) M1-IVA: Week 4 (>=30 kg)	2.18 mcg/mL Standard Deviation 1.04

SECONDARY outcome

Timeframe: Part B: From Baseline Through Week 24

LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Outcome measures

Outcome measures
Measure	Part A: ELX/TEZ/IVA n=66 Participants Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)	-1.71 lung clearance index Interval -2.11 to -1.3

Adverse Events

Part A: ELX/TEZ/IVA

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part B: ELX/TEZ/IVA

Serious events: 1 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: ELX/TEZ/IVA n=16 participants at risk Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.	Part B: ELX/TEZ/IVA n=66 participants at risk Participants in Part B weighing \<30 kg at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Infections and infestations Metapneumovirus infection	0.00% 0/16 • Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B) The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. MedDRA version 21.1 applied for Part A, MedDRA version 23.0 applied for Part B.	1.5% 1/66 • Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B) The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. MedDRA version 21.1 applied for Part A, MedDRA version 23.0 applied for Part B.
Infections and infestations Pneumonia	0.00% 0/16 • Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B) The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. MedDRA version 21.1 applied for Part A, MedDRA version 23.0 applied for Part B.	1.5% 1/66 • Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B) The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. MedDRA version 21.1 applied for Part A, MedDRA version 23.0 applied for Part B.
Infections and infestations Rhinovirus infection	0.00% 0/16 • Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B) The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. MedDRA version 21.1 applied for Part A, MedDRA version 23.0 applied for Part B.	1.5% 1/66 • Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B) The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. MedDRA version 21.1 applied for Part A, MedDRA version 23.0 applied for Part B.

Other adverse events

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER