Trial Outcomes & Findings for A Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive (TCR) CFTR Mutation and No F508del Mutation (NCT NCT05076149)

NCT ID: NCT05076149

Last Updated: 2024-06-13

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

597 participants

Primary outcome timeframe

From Baseline Through Week 24

Results posted on

2024-06-13

Participant Flow

This study was conducted in cystic fibrosis (CF) participants aged 12 years or older. It was pre-specified in the protocol to combine the data from this study with study VX20-121-102 (NCT05033080) for selected outcome measures.

A total of 597 participants were enrolled in this study, of which 24 were included in the run-in period but were not dosed in treatment period. Therefore, results are presented for only 573 participants dosed in the treatment period.

Participant milestones

Participant milestones
Measure	ELX/TEZ/IVA Following elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Overall Study STARTED	289	284
Overall Study Pooled Analysis Set	491	480
Overall Study COMPLETED	279	264
Overall Study NOT COMPLETED	10	20

Reasons for withdrawal

Reasons for withdrawal
Measure	ELX/TEZ/IVA Following elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Overall Study Adverse Event	3	9
Overall Study Withdrawal of consent (not due to AE)	1	3
Overall Study Lost to Follow-up	0	1
Overall Study Commercial drug is available for participant	0	1
Overall Study Other non compliance	1	1
Overall Study Physician Decision	0	1
Overall Study Other	5	4

Baseline Characteristics

Here, "Number Analyzed" signifies participants who were evaluable for this study specific baseline measure. This analysis set (N=565) included participants who received the dose and who had a data for this efficacy analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ELX/TEZ/IVA n=289 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA n=284 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.	Total n=573 Participants Total of all reporting groups
Age, Continuous	34.0 years STANDARD_DEVIATION 12.4 • n=289 Participants	33.3 years STANDARD_DEVIATION 12.6 • n=284 Participants	33.7 years STANDARD_DEVIATION 12.5 • n=573 Participants
Sex: Female, Male Female	145 Participants n=289 Participants	135 Participants n=284 Participants	280 Participants n=573 Participants
Sex: Female, Male Male	144 Participants n=289 Participants	149 Participants n=284 Participants	293 Participants n=573 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants n=289 Participants	4 Participants n=284 Participants	9 Participants n=573 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	261 Participants n=289 Participants	265 Participants n=284 Participants	526 Participants n=573 Participants
Race/Ethnicity, Customized Not Collected per Local Regulations	23 Participants n=289 Participants	10 Participants n=284 Participants	33 Participants n=573 Participants
Race/Ethnicity, Customized White	262 Participants n=289 Participants	270 Participants n=284 Participants	532 Participants n=573 Participants
Race/Ethnicity, Customized Asian	1 Participants n=289 Participants	1 Participants n=284 Participants	2 Participants n=573 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=289 Participants	0 Participants n=284 Participants	1 Participants n=573 Participants
Race/Ethnicity, Customized Other	1 Participants n=289 Participants	1 Participants n=284 Participants	2 Participants n=573 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=289 Participants	2 Participants n=284 Participants	3 Participants n=573 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	66.4 Percentage points STANDARD_DEVIATION 14.9 • n=286 Participants • Here, "Number Analyzed" signifies participants who were evaluable for this study specific baseline measure. This analysis set (N=565) included participants who received the dose and who had a data for this efficacy analysis.	67.2 Percentage points STANDARD_DEVIATION 14.6 • n=279 Participants • Here, "Number Analyzed" signifies participants who were evaluable for this study specific baseline measure. This analysis set (N=565) included participants who received the dose and who had a data for this efficacy analysis.	66.8 Percentage points STANDARD_DEVIATION 14.7 • n=565 Participants • Here, "Number Analyzed" signifies participants who were evaluable for this study specific baseline measure. This analysis set (N=565) included participants who received the dose and who had a data for this efficacy analysis.

PRIMARY outcome

Timeframe: From Baseline Through Week 24

Population: The Full Analysis Set (FAS) included all randomized participants who carried the intended CFTR mutation(s) and received at least 1 dose of study drug during the Treatment Period. Here "Overall Number of participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

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

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=276 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA n=268 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)	0.0 percentage points Interval -0.5 to 0.5	0.2 percentage points Interval -0.3 to 0.7

SECONDARY outcome

Timeframe: From Baseline Through Week 24

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=276 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA n=270 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Absolute Change in Sweat Chloride (SwCl)	-2.3 millimole per liter (mmol/L) Interval -3.6 to -0.9	-5.1 millimole per liter (mmol/L) Interval -6.4 to -3.7

SECONDARY outcome

Timeframe: From Baseline Through Week 24

Population: The Pooled Full Analysis Set (PFAS) included all randomized participants from this study (VX20-121-102) and from Study VX20-121-103 who carried the intended CFTR mutation(s) and received at least 1 dose of study drug during the Treatment Period. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=479 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA n=465 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102)	76.6 percentage of participants	85.8 percentage of participants

SECONDARY outcome

Timeframe: From Baseline Through Week 24

Population: PFAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=479 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA n=465 Participants Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102)	22.5 percentage of participants	30.5 percentage of participants

Adverse Events

ELX/TEZ/IVA

Serious events: 40 serious events

Other events: 253 other events

Deaths: 0 deaths

VX-121/TEZ/D-IVA

Serious events: 40 serious events

Other events: 252 other events

Deaths: 0 deaths

Serious adverse events

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

Measure	ELX/TEZ/IVA n=289 participants at risk Following ELX/TEZ/IVA run-in period of 4 weeks, subjects received ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	VX-121/TEZ/D-IVA n=284 participants at risk Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Gastrointestinal disorders Abdominal pain	8.0% 23/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.3% 15/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Gastrointestinal disorders Constipation	6.6% 19/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.3% 15/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Gastrointestinal disorders Diarrhoea	15.2% 44/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	13.0% 37/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Gastrointestinal disorders Nausea	4.5% 13/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	7.7% 22/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Gastrointestinal disorders Vomiting	6.6% 19/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	4.2% 12/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
General disorders Fatigue	10.4% 30/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	11.6% 33/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
General disorders Pyrexia	10.0% 29/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	9.9% 28/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations COVID-19	24.9% 72/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	20.1% 57/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	29.4% 85/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	24.6% 70/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations Influenza	4.8% 14/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	10.2% 29/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations Nasopharyngitis	20.8% 60/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	20.1% 57/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations Sinusitis	9.0% 26/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	3.2% 9/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations Upper respiratory tract infection	13.8% 40/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	19.4% 55/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Infections and infestations Viral upper respiratory tract infection	5.9% 17/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	7.0% 20/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Investigations Alanine aminotransferase increased	6.2% 18/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	8.5% 24/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Investigations Aspartate aminotransferase increased	6.2% 18/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	6.7% 19/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Investigations Blood creatine phosphokinase increased	5.9% 17/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	8.5% 24/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Musculoskeletal and connective tissue disorders Arthralgia	8.7% 25/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	4.9% 14/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Musculoskeletal and connective tissue disorders Back pain	5.2% 15/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.6% 16/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Nervous system disorders Headache	14.2% 41/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	18.0% 51/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Psychiatric disorders Anxiety	2.1% 6/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.6% 16/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Cough	20.8% 60/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	22.2% 63/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.3% 21/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	3.9% 11/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.6% 22/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.6% 16/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.0% 23/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	10.2% 29/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.8% 37/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	15.8% 45/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Productive cough	6.6% 19/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.6% 16/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.6% 22/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	5.6% 16/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Sinus congestion	3.5% 10/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	6.3% 18/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Sputum increased	10.0% 29/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	9.5% 27/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.
Skin and subcutaneous tissue disorders Rash	4.5% 13/289 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.	8.8% 25/284 • Day 1 up to Safety follow-up (up to 56 weeks) Safety set include all participants who received at least 1 dose of study drug during the Treatment Period.