Trial Outcomes & Findings for A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del (NCT NCT04105972)

Last Updated: 2021-08-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

176 participants

Primary outcome timeframe

From Baseline Through Week 24

Results posted on

2021-08-18

Participant Flow

A total of 176 participants were enrolled in the study. Out of those 176 participants, 1 participant was randomized but not dosed in the treatment period. Therefore, results are presented for only 175 participants.

This study was conducted in cystic fibrosis (CF) participants aged 12 years or older.

Participant milestones

Participant milestones
Measure	TEZ/IVA Following TEZ (tezacaftor)/IVA (ivacaftor) run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks.	ELX/TEZ/IVA Following TEZ/IVA run-in period of 4 weeks, participants received ELX (elexacaftor) 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Overall Study STARTED	88	87
Overall Study COMPLETED	86	86
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	TEZ/IVA Following TEZ (tezacaftor)/IVA (ivacaftor) run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks.	ELX/TEZ/IVA Following TEZ/IVA run-in period of 4 weeks, participants received ELX (elexacaftor) 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Overall Study Adverse Event	2	1

Baseline Characteristics

A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TEZ/IVA n=88 Participants Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 Participants Following 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 24 weeks.	Total n=175 Participants Total of all reporting groups
Age, Continuous	27.8 years STANDARD_DEVIATION 11.0 • n=5 Participants	27.9 years STANDARD_DEVIATION 11.8 • n=7 Participants	27.8 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	43 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	44 Participants n=7 Participants	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	83 Participants n=5 Participants	85 Participants n=7 Participants	168 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	88 Participants n=5 Participants	84 Participants n=7 Participants	172 Participants n=5 Participants
Race/Ethnicity, Customized White, Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score	73.1 units on a scale STANDARD_DEVIATION 17.6 • n=5 Participants	71.2 units on a scale STANDARD_DEVIATION 19.6 • n=7 Participants	72.2 units on a scale STANDARD_DEVIATION 18.6 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline Through Week 24

Population: Full analysis set (FAS) included all randomized participants who carried the intended CF transmembrane conductance regulator (CFTR) allele mutation and received at least 1 dose of study drug in treatment period.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=88 Participants Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 Participants Following 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 24 weeks.
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score	1.2 units on a scale Standard Error 1.5	17.1 units on a scale Standard Error 1.5

SECONDARY outcome

Timeframe: From Baseline Through Week 24

Population: FAS.

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

Outcome measures

Outcome measures
Measure	TEZ/IVA n=88 Participants Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 Participants Following 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 24 weeks.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	1.0 percentage points Standard Error 0.7	11.2 percentage points Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline Through Week 24

Population: FAS.

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=88 Participants Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 Participants Following 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 24 weeks.
Absolute Change in Sweat Chloride (SwCl)	-3.4 millimole per liter (mmol/L) Standard Error 1.2	-46.2 millimole per liter (mmol/L) Standard Error 1.3

SECONDARY outcome

Timeframe: From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)

Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=88 Participants Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 Participants Following 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 24 weeks.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants With TEAEs	81 participants	77 participants
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants With SAEs	14 participants	5 participants

Adverse Events

TEZ/IVA

Serious events: 14 serious events

Other events: 72 other events

Deaths: 0 deaths

ELX/TEZ/IVA

Serious events: 5 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TEZ/IVA n=88 participants at risk Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 participants at risk Following 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 24 weeks.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Cardiac disorders Extrasystoles	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Gastrointestinal disorders Distal intestinal obstruction syndrome	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	10.2% 9/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Infections and infestations Lower respiratory tract infection	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Investigations Alanine aminotransferase increased	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Metabolism and nutrition disorders Type 3 diabetes mellitus	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Psychiatric disorders Anxiety	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Psychiatric disorders Depression	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Psychiatric disorders Insomnia	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Psychiatric disorders Obsessive-compulsive disorder	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Psychiatric disorders Psychotic disorder	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Renal and urinary disorders Nephrolithiasis	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	0.00% 0/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)

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

Measure	TEZ/IVA n=88 participants at risk Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	ELX/TEZ/IVA n=87 participants at risk Following 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 24 weeks.
Gastrointestinal disorders Abdominal pain	8.0% 7/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	4.6% 4/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Gastrointestinal disorders Diarrhoea	8.0% 7/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	9.2% 8/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	36.4% 32/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	11.5% 10/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Infections and infestations Nasopharyngitis	14.8% 13/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	19.5% 17/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Infections and infestations Upper respiratory tract infection	5.7% 5/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	10.3% 9/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Investigations Alanine aminotransferase increased	1.1% 1/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	6.9% 6/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Investigations Aspartate aminotransferase increased	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	5.7% 5/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Investigations Bacterial test positive	5.7% 5/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	1.1% 1/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Nervous system disorders Headache	20.5% 18/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	28.7% 25/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Cough	26.1% 23/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	12.6% 11/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.8% 6/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	3.4% 3/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	6.9% 6/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.0% 7/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	12.6% 11/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Productive cough	3.4% 3/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	9.2% 8/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Respiratory, thoracic and mediastinal disorders Sputum increased	18.2% 16/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	11.5% 10/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)
Skin and subcutaneous tissue disorders Rash	0.00% 0/88 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)	8.0% 7/87 • From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)