Trial Outcomes & Findings for A Study to Assess the Effect of ELX/TEZ/IVA on Glucose Tolerance in Participants With Cystic Fibrosis (CF) (NCT NCT04599465)

Last Updated: 2023-08-03

Results Overview

Baseline 2-hour post-OGTT blood glucose level was defined as the average of valid pre-dose measurements at screening and Day 1. OGTT results were considered valid only when the participant was fasting for at least 8 hours.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

69 participants

Primary outcome timeframe

Baseline, Week 36 and 48

Results posted on

2023-08-03

Participant Flow

This study was conducted in participants with cystic fibrosis (CF) aged 12 years and older who are heterozygous for the F508del mutation and a minimal function mutation (F/MF genotypes), with abnormal glucose metabolism.

Participant milestones

Participant milestones
Measure	ELX/TEZ/IVA Participants received elexacaftor (ELX) 200 mg/tezacaftor (TEZ)100 mg ivacaftor (IVA) 150 mg in the morning and IVA 150 mg in the evening.
Overall Study STARTED	69
Overall Study COMPLETED	66
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	ELX/TEZ/IVA Participants received elexacaftor (ELX) 200 mg/tezacaftor (TEZ)100 mg ivacaftor (IVA) 150 mg in the morning and IVA 150 mg in the evening.
Overall Study Physician Decision	1
Overall Study Withdrawal of consent (not due to AE)	2

Baseline Characteristics

A Study to Assess the Effect of ELX/TEZ/IVA on Glucose Tolerance in Participants With Cystic Fibrosis (CF)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ELX/TEZ/IVA n=69 Participants Participants received ELX 200 mg /TEZ 100 mg /IVA 150 mg in the morning and IVA 150 mg in the evening.
Age, Customized Less than (<)18 years	19 Participants n=5 Participants
Age, Customized More than or equal to (≥)18 years	50 Participants n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	8 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	41 Participants n=5 Participants
Race/Ethnicity, Customized Not collected per local regulations	20 Participants n=5 Participants
Race/Ethnicity, Customized White	48 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
2-hour Post-OGTT Blood Glucose Levels	217.6 milligrams per deciliter (mg/dl) STANDARD_DEVIATION 73.1 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 36 and 48

Population: The Full Analysis Set (FAS) will include all enrolled participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=66 Participants Participants received ELX 200 mg /TEZ 100 mg/IVA 150 mg in the morning and IVA 150 mg in the evening.
Change From Baseline in 2-hour Blood Glucose Levels Following an OGTT to the Average of Week 36 and Week 48	-35.0 milligrams per deciliter (mg/dl) Interval -49.2 to -20.7

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: FAS. Here, "Overall Number of Participants Analyzed" signifies the number participants with non-missing dysglycemia categorization at Week 48 among participants with abnormal glucose tolerance at baseline.

Baseline dysglycemia category was defined as the most recent non-missing measurement before the first dose of study drug in the treatment period. Improvement in dysglycemia is a change from cystic fibrosis-related diabetes (CFRD) at baseline to impaired glucose tolerance (IGT)/normal glucose tolerance (NGT) at Week 48 OR change from IGT at baseline to NGT at Week 48. CFRD: 2-hour post-OGTT blood glucose level ≥200 mg/dL or fasting blood glucose level ≥126 mg/dL; IGT: 2-hour post-OGTT blood glucose level ≥140 to \<200 mg/dL and fasting blood glucose level \<126 mg/dL; NGT: 2 hour post-OGTT blood glucose level \<140 mg/dL and fasting blood glucose level \<126 mg/dL.

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=53 Participants Participants received ELX 200 mg /TEZ 100 mg/IVA 150 mg in the morning and IVA 150 mg in the evening.
Percentage of Participants With Improvement in Dysglycemia Categorization at Week 48	37.7 percentage of participants Interval 24.8 to 52.1

SECONDARY outcome

Timeframe: Day 1 up to Week 52

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

Outcome measures

Outcome measures
Measure	ELX/TEZ/IVA n=69 Participants Participants received ELX 200 mg /TEZ 100 mg/IVA 150 mg in the morning and IVA 150 mg in the evening.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with TEAEs	67 Participants
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with SAEs	6 Participants

Adverse Events

ELX/TEZ/IVA

Serious events: 6 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ELX/TEZ/IVA n=69 participants at risk Participants received ELX 200 mg/TEZ 100 mg/IVA 150 mg in the morning and IVA 150 mg in the evening.
Gastrointestinal disorders Gastritis	1.4% 1/69 • Day 1 up to Week 52
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	1.4% 1/69 • Day 1 up to Week 52
Infections and infestations Influenza	1.4% 1/69 • Day 1 up to Week 52
Infections and infestations Sinusitis	1.4% 1/69 • Day 1 up to Week 52
Injury, poisoning and procedural complications Clavicle fracture	1.4% 1/69 • Day 1 up to Week 52
Nervous system disorders Headache	1.4% 1/69 • Day 1 up to Week 52
Reproductive system and breast disorders Heavy menstrual bleeding	1.4% 1/69 • Day 1 up to Week 52
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.4% 1/69 • Day 1 up to Week 52

Other adverse events

Other adverse events
Measure	ELX/TEZ/IVA n=69 participants at risk Participants received ELX 200 mg/TEZ 100 mg/IVA 150 mg in the morning and IVA 150 mg in the evening.
Gastrointestinal disorders Abdominal pain	13.0% 9/69 • Day 1 up to Week 52
Gastrointestinal disorders Abdominal pain upper	11.6% 8/69 • Day 1 up to Week 52
Gastrointestinal disorders Diarrhoea	18.8% 13/69 • Day 1 up to Week 52
Gastrointestinal disorders Nausea	8.7% 6/69 • Day 1 up to Week 52
Gastrointestinal disorders Vomiting	10.1% 7/69 • Day 1 up to Week 52
General disorders Fatigue	7.2% 5/69 • Day 1 up to Week 52
General disorders Pyrexia	23.2% 16/69 • Day 1 up to Week 52
Immune system disorders Immunisation reaction	8.7% 6/69 • Day 1 up to Week 52
Infections and infestations COVID-19	31.9% 22/69 • Day 1 up to Week 52
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	14.5% 10/69 • Day 1 up to Week 52
Infections and infestations Influenza	8.7% 6/69 • Day 1 up to Week 52
Infections and infestations Nasopharyngitis	21.7% 15/69 • Day 1 up to Week 52
Infections and infestations Rhinitis	10.1% 7/69 • Day 1 up to Week 52
Infections and infestations Tonsillitis	5.8% 4/69 • Day 1 up to Week 52
Infections and infestations Upper respiratory tract infection	5.8% 4/69 • Day 1 up to Week 52
Investigations Alanine aminotransferase increased	8.7% 6/69 • Day 1 up to Week 52
Investigations Aspartate aminotransferase increased	7.2% 5/69 • Day 1 up to Week 52
Investigations Blood bilirubin increased	10.1% 7/69 • Day 1 up to Week 52
Investigations Blood creatine phosphokinase increased	7.2% 5/69 • Day 1 up to Week 52
Metabolism and nutrition disorders Hypoglycaemia	5.8% 4/69 • Day 1 up to Week 52
Nervous system disorders Headache	23.2% 16/69 • Day 1 up to Week 52
Respiratory, thoracic and mediastinal disorders Cough	15.9% 11/69 • Day 1 up to Week 52
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.8% 4/69 • Day 1 up to Week 52
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.6% 8/69 • Day 1 up to Week 52
Respiratory, thoracic and mediastinal disorders Productive cough	7.2% 5/69 • Day 1 up to Week 52
Respiratory, thoracic and mediastinal disorders Sputum increased	17.4% 12/69 • Day 1 up to Week 52
Skin and subcutaneous tissue disorders Acne	5.8% 4/69 • Day 1 up to Week 52
Skin and subcutaneous tissue disorders Rash	10.1% 7/69 • Day 1 up to Week 52

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