Trial Outcomes & Findings for Long-term Safety of Lumacaftor/Ivacaftor in Participants With Cystic Fibrosis Who Are Homozygous for F508del and 12 to <24 Months of Age at Treatment Initiation (NCT NCT04235140)
NCT ID: NCT04235140
Last Updated: 2024-09-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
52 participants
Primary outcome timeframe
Day 1 up to Week 120
Results posted on
2024-09-19
Participant Flow
The study was conducted in participants with cystic fibrosis (CF) aged 12 months through less than (\<) 24 months of age at treatment initiation who were homozygous for F508del and participants who completed the 24-week treatment period along with the safety follow-up in study VX16-809-122 (NCT03601637) Part B.
Participant milestones
| Measure |
LUM/IVA
Participants weighing 7 to less than (\<) 9 kilograms (kg) received LUM 75 milligrams (mg)/IVA 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 9 to \<14 kg received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants weighing greater than or equal to (\>=)14 kg received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
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|---|---|
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Overall Study
STARTED
|
52
|
|
Overall Study
Rollover Participants
|
39
|
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Overall Study
Lumacaftor (LUM)/ Ivacaftor (IVA)-Naïve Participants
|
13
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
14
|
Reasons for withdrawal
| Measure |
LUM/IVA
Participants weighing 7 to less than (\<) 9 kilograms (kg) received LUM 75 milligrams (mg)/IVA 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 9 to \<14 kg received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants weighing greater than or equal to (\>=)14 kg received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
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|---|---|
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Overall Study
Adverse Event
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Withdrawal of consent (not due to AE)
|
4
|
|
Overall Study
Commercial drug is available for participants
|
7
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Baseline Characteristics
Long-term Safety of Lumacaftor/Ivacaftor in Participants With Cystic Fibrosis Who Are Homozygous for F508del and 12 to <24 Months of Age at Treatment Initiation
Baseline characteristics by cohort
| Measure |
LUM/IVA
n=52 Participants
Participants weighing 7 to \<9 kg received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to \<14 kg received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants \>=14 kg received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
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|---|---|
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Age, Continuous
|
18.8 months
STANDARD_DEVIATION 3.32 • n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
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Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
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Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=5 Participants
|
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Race/Ethnicity, Customized
Not Hispanic or Latino
|
43 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not collected per local regulations
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
40 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
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
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Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
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Race/Ethnicity, Customized
More than one race
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to Week 120Population: Safety set included all participants who are exposed to any amount of study drug in this study.
Outcome measures
| Measure |
LUM/IVA
n=52 Participants
Participants weighing 7 to \<9 kg received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to \<14 kg received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants \>=14 kg received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
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|---|---|
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Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants with TEAEs
|
52 Participants
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Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
12 Participants
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SECONDARY outcome
Timeframe: From Baseline at Week 96Population: The Full Analysis Set (FAS) included all participants who were enrolled and dosed in Study 124. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
LUM/IVA
n=22 Participants
Participants weighing 7 to \<9 kg received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to \<14 kg received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants \>=14 kg received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
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|---|---|
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Absolute Change in Sweat Chloride (SwCl)
|
-21.0 millimole per liter (mmol/L)
Standard Deviation 14.9
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Adverse Events
LUM/IVA
Serious events: 12 serious events
Other events: 50 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LUM/IVA
n=52 participants at risk
Participants weighing 7 to \< 9 kg at Day 1 received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to \<14 kg at Day 1 received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants weighing \>=14 kg at Day 1 received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
|
|---|---|
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Gastrointestinal disorders
Constipation
|
3.8%
2/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Immune system disorders
Anaphylactic reaction
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
COVID-19
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
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Infections and infestations
Cellulitis orbital
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
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Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
11.5%
6/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Lower respiratory tract infection viral
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Oral herpes
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Parainfluenzae virus infection
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Sinusitis
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Injury, poisoning and procedural complications
Near drowning
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
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Injury, poisoning and procedural complications
Procedural pain
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
1.9%
1/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
Other adverse events
| Measure |
LUM/IVA
n=52 participants at risk
Participants weighing 7 to \< 9 kg at Day 1 received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to \<14 kg at Day 1 received LUM 100 mg/IVA 125 mg q12h in the treatment period of 96 weeks. Participants weighing \>=14 kg at Day 1 received LUM 150 mg/IVA 188 mg FDC q12h in the treatment period of 96 weeks.
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|---|---|
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Gastrointestinal disorders
Abdominal pain upper
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Gastrointestinal disorders
Constipation
|
26.9%
14/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.5%
6/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Gastrointestinal disorders
Vomiting
|
26.9%
14/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
General disorders
Pyrexia
|
28.8%
15/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Bronchitis
|
7.7%
4/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
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Infections and infestations
COVID-19
|
23.1%
12/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Conjunctivitis
|
7.7%
4/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Croup infectious
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Ear infection
|
23.1%
12/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Gastroenteritis
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
26.9%
14/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Molluscum contagiosum
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Otitis media
|
9.6%
5/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Otitis media acute
|
7.7%
4/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Respiratory syncytial virus infection
|
7.7%
4/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Sinusitis
|
7.7%
4/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Upper respiratory tract infection
|
30.8%
16/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Urinary tract infection
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Investigations
Alanine aminotransferase increased
|
15.4%
8/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Investigations
Aspartate aminotransferase increased
|
11.5%
6/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Investigations
Blood creatine phosphokinase increased
|
5.8%
3/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Investigations
Pseudomonas test positive
|
13.5%
7/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
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Investigations
SARS-CoV-2 test positive
|
9.6%
5/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
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Respiratory, thoracic and mediastinal disorders
Cough
|
48.1%
25/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
17.3%
9/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
28.8%
15/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.5%
6/52 • Day 1 to Week 120
Safety set included all participants who are exposed to any amount of study drug in this study.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place