Trial Outcomes & Findings for A Study to Evaluate Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Have a 3849 + 10KB C→T or D1152H CFTR Mutation (NCT NCT03068312)

NCT ID: NCT03068312

Last Updated: 2020-02-26

Results Overview

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 38 participants
• Primary outcome timeframe: From baseline through 8 weeks
• Results posted on: 2020-02-26

Participant Flow

This study was conducted in participants with cystic fibrosis (CF).

Participant milestones

Measure	Sequence 1: First Ivacaftor (IVA) Then Placebo Participants received IVA 150 milligram (mg) every 12 hours (q12h) for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods.	Sequence 2: First Placebo Then IVA Participants received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA 150 mg q12h for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods.
Overall Study STARTED	19	19
Overall Study COMPLETED	19	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Have a 3849 + 10KB C→T or D1152H CFTR Mutation

Baseline characteristics by cohort

Measure	Sequence 1: First IVA Then Placebo n=19 Participants Participants received IVA 150 mg q12h for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods.	Sequence 2: First Placebo Then IVA n=19 Participants Participants received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA 150 mg q12h for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods.	Total n=38 Participants Total of all reporting groups
Age, Continuous	32.6 years STANDARD_DEVIATION 15.3 • n=5 Participants	32.1 years STANDARD_DEVIATION 15.6 • n=7 Participants	32.3 years STANDARD_DEVIATION 15.2 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Lung Clearance Index 2.5 (LCI2.5)	12.74 lung clearance index STANDARD_DEVIATION 4.04 • n=5 Participants	13.19 lung clearance index STANDARD_DEVIATION 5.45 • n=7 Participants	12.96 lung clearance index STANDARD_DEVIATION 4.74 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline through 8 weeks

Population: The Full Analysis Set (FAS) included all randomized subjects who carried the intended CFTR allele mutation and received at least 1 dose of study drug.

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Outcome measures

Measure	Placebo n=37 Participants All participants who received placebo matched to IVA for 8 weeks in treatment period 1 or 2.	Ivacaftor n=37 Participants All participants who received IVA for 8 weeks in treatment period 1 or 2.
Change in Lung Clearance Index 2.5 (LCI2.5)	0.20 lung clearance index Standard Error 0.19	-0.46 lung clearance index Standard Error 0.19

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Ivacaftor

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=38 participants at risk All participants who received placebo matched to IVA for 8 weeks in treatment period 1 or 2.	Ivacaftor n=38 participants at risk All participants who received IVA for 8 weeks in treatment period 1 or 2.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	2.6% 1/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Gastrointestinal disorders Pancreatitis	2.6% 1/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	0.00% 0/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	2.6% 1/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	0.00% 0/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)

Other adverse events

Measure	Placebo n=38 participants at risk All participants who received placebo matched to IVA for 8 weeks in treatment period 1 or 2.	Ivacaftor n=38 participants at risk All participants who received IVA for 8 weeks in treatment period 1 or 2.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.3% 2/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	7.9% 3/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Nervous system disorders Headache	5.3% 2/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	2.6% 1/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
General disorders Pyrexia	2.6% 1/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	5.3% 2/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
General disorders Malaise	5.3% 2/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	0.00% 0/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Gastrointestinal disorders Aphthous ulcer	5.3% 2/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	0.00% 0/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	5.3% 2/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	13.2% 5/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Infections and infestations Upper respiratory tract infection	15.8% 6/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	7.9% 3/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)
Infections and infestations Viral upper respiratory tract infection	23.7% 9/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)	2.6% 1/38 • From first dose of study drug up to safety follow-up visit (up to Week 28)

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: +1 617 341 6777

Email: medicalinfo@vrtx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER