Trial Outcomes & Findings for A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Participants With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation (NCT NCT03277196)
NCT ID: NCT03277196
Last Updated: 2024-10-23
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
86 participants
Primary outcome timeframe
Day 1 up to Week 120
Results posted on
2024-10-23
Participant Flow
This study was planned to include 2 arms: an ivacaftor (IVA) arm (open-label, 96-week treatment period) and an observational arm. However, there were no participants enrolled in the observational arm. A total of 86 participants enrolled in the Ivacaftor arm.
Rollover participants (who completed parent study VX15-770-124 \[NCT02725567\] Part B or Part A/B) and IVA-naïve participants (who participated in study VX15-770-124 Part A only or who did not participate in VX15-770-124 and were less than (\<) 24 months of age at the Day 1 of current study \[VX15-770-126\]) were enrolled in this study.
Participant milestones
| Measure |
Ivacaftor Treatment
Participants less than (\<) 24 months of age and weighing 5 to less than (\<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants more than or equal (\>=) 24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing more than or equal to (\>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Overall Study
STARTED
|
86
|
|
Overall Study
Rollover Participants
|
38
|
|
Overall Study
IVA-Naïve Participants
|
48
|
|
Overall Study
COMPLETED
|
58
|
|
Overall Study
NOT COMPLETED
|
28
|
Reasons for withdrawal
| Measure |
Ivacaftor Treatment
Participants less than (\<) 24 months of age and weighing 5 to less than (\<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants more than or equal (\>=) 24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing more than or equal to (\>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Overall Study
Commercial Drug is Available for Participants
|
20
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Withdrawal of Consent (not due to AE)
|
3
|
|
Overall Study
Other
|
2
|
Baseline Characteristics
A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Participants With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation
Baseline characteristics by cohort
| Measure |
Ivacaftor Treatment
n=86 Participants
Participants \<24 months of age and weighing 5 \<7 kg received 25 mg IVA q12h, 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants \>=24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing \>=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Age, Continuous
|
10.2 months
STANDARD_DEVIATION 5.19 • n=99 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
2 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
79 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not collected per local regulations
|
3 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
82 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to Week 120Population: Safety Set included all participants who received at least 1 dose of study drug in this study.
Outcome measures
| Measure |
Ivacaftor Treatment
n=86 Participants
Participants \<24 months of age and weighing 5 \<7 kg received 25 mg IVA q12h, 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants \>=24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing \>=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with TEAEs
|
85 Participants
|
|
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with SAEs
|
21 Participants
|
SECONDARY outcome
Timeframe: From Baseline at Week 96Population: The Full Analysis Set (FAS) included all participants who were enrolled and have at least 1 post baseline efficacy assessment in this study. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
Ivacaftor Treatment
n=33 Participants
Participants \<24 months of age and weighing 5 \<7 kg received 25 mg IVA q12h, 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants \>=24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing \>=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Absolute Change in Sweat Chloride
|
-55.3 millimole per liter (mmol/L)
Standard Deviation 25.0
|
Adverse Events
Ivacaftor Arm
Serious events: 21 serious events
Other events: 83 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ivacaftor Arm
n=86 participants at risk
Participants \<24 months of age and weighing 5 \<7 kg received 25 mg IVA q12h, 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants \>=24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing \>=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Endocrine disorders
Adrenocortical insufficiency acute
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Gastrointestinal disorders
Constipation
|
2.3%
2/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
General disorders
Pyrexia
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Bronchiolitis
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Bronchitis
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Gastroenteritis
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Gastroenteritis viral
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
10.5%
9/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Lower respiratory tract infection viral
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Parainfluenzae virus infection
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Periorbital cellulitis
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Respiratory syncytial virus infection
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Rhinovirus infection
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Viral infection
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Viral rash
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Electrocardiogram QT shortened
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Electroencephalogram abnormal
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Pseudomonas test positive
|
2.3%
2/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Metabolism and nutrition disorders
Malnutrition
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Product Issues
Device dislocation
|
1.2%
1/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
Other adverse events
| Measure |
Ivacaftor Arm
n=86 participants at risk
Participants \<24 months of age and weighing 5 \<7 kg received 25 mg IVA q12h, 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h.
Participants \>=24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing \>=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
15.1%
13/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Gastrointestinal disorders
Diarrhoea
|
17.4%
15/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Gastrointestinal disorders
Teething
|
8.1%
7/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Gastrointestinal disorders
Vomiting
|
25.6%
22/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
General disorders
Pyrexia
|
39.5%
34/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Immune system disorders
Seasonal allergy
|
7.0%
6/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Conjunctivitis
|
10.5%
9/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Ear infection
|
22.1%
19/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Gastroenteritis
|
10.5%
9/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
15.1%
13/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Influenza
|
9.3%
8/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Nasopharyngitis
|
11.6%
10/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Otitis media
|
11.6%
10/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Respiratory tract infection viral
|
5.8%
5/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Rhinitis
|
12.8%
11/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Sinusitis
|
7.0%
6/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Tonsillitis
|
7.0%
6/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Upper respiratory tract infection
|
27.9%
24/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
7.0%
6/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Alanine aminotransferase increased
|
8.1%
7/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Gamma-glutamyltransferase increased
|
7.0%
6/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Haemophilus test positive
|
7.0%
6/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Investigations
Pseudomonas test positive
|
10.5%
9/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
69.8%
60/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
15.1%
13/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
38.4%
33/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Skin and subcutaneous tissue disorders
Dermatitis diaper
|
5.8%
5/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
24.4%
21/86 • Day 1 up to Week 120
Safety Set included all participants who received at least 1 dose of study drug in this study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place