Trial Outcomes & Findings for A Study Evaluating Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis and F/MF Genotypes (NCT NCT04353817)
NCT ID: NCT04353817
Last Updated: 2022-07-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
121 participants
Primary outcome timeframe
From Baseline Through Week 24
Results posted on
2022-07-26
Participant Flow
This study was conducted in cystic fibrosis (CF) participants aged 6 through 11 years of age.
Participant milestones
| Measure |
Placebo
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
Participants weighing less than (\<) 30 kilograms (kg) at screening received ELX 100 mg once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) and participants weighing greater than equals to (\>=) 30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
61
|
60
|
|
Overall Study
COMPLETED
|
61
|
59
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
Participants weighing less than (\<) 30 kilograms (kg) at screening received ELX 100 mg once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) and participants weighing greater than equals to (\>=) 30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
A Study Evaluating Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis and F/MF Genotypes
Baseline characteristics by cohort
| Measure |
Placebo
n=61 Participants
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
n=60 Participants
Participants weighing \<30 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
|
Total
n=121 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9.2 years
STANDARD_DEVIATION 1.7 • n=5 Participants
|
9.1 years
STANDARD_DEVIATION 1.8 • n=7 Participants
|
9.2 years
STANDARD_DEVIATION 1.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
42 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Lung Clearance Index2.5 (LCI2.5)
|
9.75 index
STANDARD_DEVIATION 1.95 • n=5 Participants
|
10.26 index
STANDARD_DEVIATION 2.22 • n=7 Participants
|
10.01 index
STANDARD_DEVIATION 2.09 • n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline Through Week 24Population: Full analysis set (FAS) included all randomized participants who carry the intended CFTR allele mutation and receive at least 1 dose of study drug.
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 |
Placebo
n=61 Participants
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
n=60 Participants
Participants weighing \<30 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
|
|---|---|---|
|
Absolute Change in Lung Clearance Index 2.5 (LCI2.5)
|
-0.02 index
Standard Error 0.16
|
-2.29 index
Standard Error 0.16
|
SECONDARY outcome
Timeframe: From Baseline Through Week 24Population: FAS.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
Placebo
n=61 Participants
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
n=60 Participants
Participants weighing \<30 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at screening 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)
|
-0.9 millimole per liter (mmol/L)
Standard Error 1.5
|
-52.1 millimole per liter (mmol/L)
Standard Error 1.5
|
SECONDARY outcome
Timeframe: Day 1 up to Week 28Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period.
Outcome measures
| Measure |
Placebo
n=61 Participants
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
n=60 Participants
Participants weighing \<30 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at screening 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
|
57 participants
|
48 participants
|
|
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants With SAEs
|
9 participants
|
4 participants
|
Adverse Events
Placebo
Serious events: 9 serious events
Other events: 53 other events
Deaths: 0 deaths
ELX/TEZ/IVA
Serious events: 4 serious events
Other events: 46 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=61 participants at risk
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
n=60 participants at risk
Participants weighing \<30 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at screening 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
Lymphadenitis
|
1.6%
1/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Congenital, familial and genetic disorders
Phimosis
|
0.00%
0/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
1.6%
1/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Intussusception
|
1.6%
1/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
General disorders
General physical health deterioration
|
1.6%
1/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
4.9%
3/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Infections and infestations
Pneumonia pseudomonal
|
1.6%
1/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Infections and infestations
Varicella zoster virus infection
|
0.00%
0/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
|
Investigations
Bacterial test positive
|
0.00%
0/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
1.6%
1/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
Other adverse events
| Measure |
Placebo
n=61 participants at risk
Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.
|
ELX/TEZ/IVA
n=60 participants at risk
Participants weighing \<30 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
27.9%
17/61 • Day 1 up to Week 28
|
8.3%
5/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.2%
5/61 • Day 1 up to Week 28
|
6.7%
4/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Diarrhoea
|
9.8%
6/61 • Day 1 up to Week 28
|
6.7%
4/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Nausea
|
8.2%
5/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Steatorrhoea
|
0.00%
0/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Vomiting
|
6.6%
4/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
General disorders
Fatigue
|
8.2%
5/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
23.0%
14/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
|
Infections and infestations
Nasopharyngitis
|
14.8%
9/61 • Day 1 up to Week 28
|
11.7%
7/60 • Day 1 up to Week 28
|
|
Infections and infestations
Rhinitis
|
8.2%
5/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
Infections and infestations
Upper respiratory tract infection
|
8.2%
5/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
Investigations
Alanine aminotransferase increased
|
4.9%
3/61 • Day 1 up to Week 28
|
8.3%
5/60 • Day 1 up to Week 28
|
|
Investigations
Aspartate aminotransferase increased
|
1.6%
1/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
Investigations
Bacterial test positive
|
6.6%
4/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Investigations
Forced expiratory volume decreased
|
6.6%
4/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Investigations
Staphylococcus test positive
|
1.6%
1/61 • Day 1 up to Week 28
|
6.7%
4/60 • Day 1 up to Week 28
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.6%
4/61 • Day 1 up to Week 28
|
1.7%
1/60 • Day 1 up to Week 28
|
|
Nervous system disorders
Headache
|
19.7%
12/61 • Day 1 up to Week 28
|
30.0%
18/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
42.6%
26/61 • Day 1 up to Week 28
|
23.3%
14/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.9%
3/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
6.6%
4/61 • Day 1 up to Week 28
|
0.00%
0/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
19.7%
12/61 • Day 1 up to Week 28
|
5.0%
3/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
9.8%
6/61 • Day 1 up to Week 28
|
11.7%
7/60 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
11.5%
7/61 • Day 1 up to Week 28
|
11.7%
7/60 • Day 1 up to Week 28
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/61 • Day 1 up to Week 28
|
6.7%
4/60 • Day 1 up to Week 28
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.9%
3/61 • Day 1 up to Week 28
|
10.0%
6/60 • Day 1 up to Week 28
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER