Trial Outcomes & Findings for A Study Evaluating the Long-term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis (CF) Particpants 6 Years and Older and F/MF Genotypes (NCT NCT04545515)
NCT ID: NCT04545515
Last Updated: 2024-05-08
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
120 participants
Primary outcome timeframe
From Baseline up to Week 100
Results posted on
2024-05-08
Participant Flow
A total of 120 participants from the parent study VX19-445-116 (NCT04353817) were enrolled in this study.
Participant milestones
| Measure |
ELX/TEZ/IVA
Participants 6 to less than \<12 year of age and weighing \<30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Overall Study
STARTED
|
120
|
|
Overall Study
Placebo-ELX/TEZ/IVA
|
61
|
|
Overall Study
ELX/TEZ/IVA-ELX/TEZ/IVA
|
59
|
|
Overall Study
COMPLETED
|
110
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
ELX/TEZ/IVA
Participants 6 to less than \<12 year of age and weighing \<30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal of consent (not due to AE)
|
2
|
|
Overall Study
Commercial drug is available for participant
|
7
|
Baseline Characteristics
A Study Evaluating the Long-term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis (CF) Particpants 6 Years and Older and F/MF Genotypes
Baseline characteristics by cohort
| Measure |
ELX/TEZ/IVA
n=120 Participants
Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Age, Continuous
|
9.1 years
STANDARD_DEVIATION 1.7 • n=99 Participants
|
|
Sex: Female, Male
Female
|
69 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
90 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not collected per local regulations
|
29 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
87 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not collected per local Regulations
|
28 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Multiracial
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From Baseline up to Week 100Population: The Open-label Safety Set (OL-SS) included all participants who had received at least 1 dose of study drug in the Open label extension (OLE) study.
Outcome measures
| Measure |
ELX/TEZ/IVA
n=120 Participants
Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with TEAEs
|
118 Participants
|
|
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
13 Participants
|
SECONDARY outcome
Timeframe: From Parent Study Baseline to Week 96Population: OL Full Analysis Set (OL-FAS) included all enrolled participants who received at least 1 dose of study drug in this study. Data were planned to be presented as per parent study reporting groups (i.e. Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA). Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome at Week 96 and "Number Analyzed" signifies participants who were evaluable in the specified parent study reporting group.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
ELX/TEZ/IVA
n=98 Participants
Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)
Placebo (Parent study)-ELX/TEZ/IVA (Current study)
|
-57.3 millimole per liter (mmol/L)
Standard Error 2.2
|
|
Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)
ELX/TEZ/IVA (Parent study)-ELX/TEZ/IVA (Current study)
|
-57.5 millimole per liter (mmol/L)
Standard Error 2.3
|
SECONDARY outcome
Timeframe: From Parent Study Baseline to Week 96Population: OL-FAS. Data were planned to be presented as per parent study reporting groups (i.e. Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA). Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome at Week 96 and "Number Analyzed" signifies participants who were evaluable in the specified parent study reporting group.
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.
Outcome measures
| Measure |
ELX/TEZ/IVA
n=104 Participants
Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Absolute Change From Parent Study Baseline in Lung Clearance Index 2.5 (LCI2.5)
Placebo (Parent study)-ELX/TEZ/IVA (Current study)
|
-1.74 Index
Standard Error 0.18
|
|
Absolute Change From Parent Study Baseline in Lung Clearance Index 2.5 (LCI2.5)
ELX/TEZ/IVA (Parent study)-ELX/TEZ/IVA (Current study)
|
-2.35 Index
Standard Error 0.19
|
Adverse Events
ELX/TEZ/IVA
Serious events: 13 serious events
Other events: 118 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ELX/TEZ/IVA
n=120 participants at risk
Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Enteritis
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Steatorrhoea
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
General disorders
General physical health deterioration
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Bacterial disease carrier
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
1.7%
2/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Pneumonia pseudomonal
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Investigations
Blood glucose increased
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Metabolism and nutrition disorders
Weight gain poor
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Renal and urinary disorders
Haematuria
|
0.83%
1/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
Other adverse events
| Measure |
ELX/TEZ/IVA
n=120 participants at risk
Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks.
|
|---|---|
|
Ear and labyrinth disorders
Ear pain
|
6.7%
8/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Eye disorders
Conjunctivitis allergic
|
5.8%
7/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Abdominal pain
|
22.5%
27/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.2%
11/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Constipation
|
6.7%
8/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
15/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Nausea
|
7.5%
9/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
24/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
General disorders
Fatigue
|
5.0%
6/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
General disorders
Pyrexia
|
40.0%
48/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Immune system disorders
Immunisation reaction
|
6.7%
8/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Bacterial disease carrier
|
6.7%
8/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
COVID-19
|
58.3%
70/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Hordeolum
|
8.3%
10/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
15.8%
19/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Influenza
|
9.2%
11/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Nasopharyngitis
|
45.0%
54/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Rhinitis
|
24.2%
29/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Upper respiratory tract infection
|
30.8%
37/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
10.8%
13/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Investigations
Alanine aminotransferase increased
|
9.2%
11/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
6/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Investigations
Bacterial test positive
|
5.8%
7/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Investigations
SARS-CoV-2 test positive
|
10.0%
12/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Investigations
Staphylococcus test positive
|
7.5%
9/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
6/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.5%
9/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Nervous system disorders
Headache
|
37.5%
45/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
51.7%
62/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
10.8%
13/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
26.7%
32/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
14.2%
17/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
18.3%
22/120 • Day 1 up to Week 100
The OL-SS included all participants who had received at least 1 dose of study drug in the OLE study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place