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

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03068312
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy of ivacaftor treatment in subjects with CF 6 years of age and older who have a 3849 + 10KB C→T or D1152H CFTR mutation.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Ivacaftor; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Are 6 Years of Age and Older and Have Either a 3849 + 10KB C→T or D1152H-CFTR Mutation
• Actual Study Start Date: Jul 18, 2017
• Actual Primary Completion Date: Dec 18, 2018
• Actual Study Completion Date: Dec 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Ivacaftor; IVA 150 mg tablet.; Other Names: VX-770 IVA ; Drug: Placebo; Placebo matched to IVA tablet.
Experimental: 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.	Drug: Ivacaftor; IVA 150 mg tablet.; Other Names: VX-770 IVA ; Drug: Placebo; Placebo matched to IVA tablet.

Outcome Measures

Primary Outcome Measures

1. Change in Lung Clearance Index 2.5 (LCI2.5) [From baseline through 8 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed diagnosis of CF based on protocol-specified clinical features and at least one of the following: increased sweat chloride level, identification of 2 CF causing mutations, or demonstration of abnormal nasal epithelial ion transport.

• A 3849 + 10KB C→T or D1152H mutation on at least 1 CFTR allele.

• FEV1 ≥40% of predicted and ≤105% of predicted at screening.

Exclusion Criteria:

• A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation.

• History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.

• Ongoing or prior participation in an investigational drug study within 30 days before the Screening Visit.

• Protocol-specified abnormal laboratory values at the Screening Visit

• For subjects <18 years of age at the Screening Visit, evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination (OE) at the Screening Visit.

• Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1.

• Pregnant, breastfeeding, or planning to become pregnant during the study.

• Sexually active subjects of reproductive potential must be willing to use appropriate contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hadassah Medical Organization	Jerusalem		Israel

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 20, 2016
• Statistical Analysis Plan - Oct 19, 2018

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03068312
• Other Study ID Numbers: VX16-770-127; 2017-000457-39
• First Posted: Mar 1, 2017
• Last Update Posted: Feb 26, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor

Study Results

Participant Flow

Pre-assignment Detail	This study was conducted in participants with cystic fibrosis (CF).

Arm/Group Title	Sequence 1: First Ivacaftor (IVA) Then Placebo	Sequence 2: First Placebo Then IVA
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequence 1: First IVA Then Placebo	Sequence 2: First Placebo Then IVA	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	19	19	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.6 (15.3)	32.1 (15.6)	32.3 (15.2)
Sex: Female, Male (Count of Participants)
Female	10 52.6%	10 52.6%	20 52.6%
Male	9 47.4%	9 47.4%	18 47.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	19 100%	19 100%	38 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	19 100%	19 100%	38 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Lung Clearance Index 2.5 (LCI2.5) (lung clearance index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lung clearance index]	12.74 (4.04)	13.19 (5.45)	12.96 (4.74)

Outcome Measures

1. Primary Outcome

Title	Change in Lung Clearance Index 2.5 (LCI2.5)
Description	LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame	From baseline through 8 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Ivacaftor
Arm/Group Description	All participants who received placebo matched to IVA for 8 weeks in treatment period 1 or 2.	All participants who received IVA for 8 weeks in treatment period 1 or 2.
Measure Participants	37	37
Least Squares Mean (Standard Error) [lung clearance index]	0.20 (0.19)	-0.46 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ivacaftor
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -1.10 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From first dose of study drug up to safety follow-up visit (up to Week 28)
Arm/Group Title	Placebo		Ivacaftor
Arm/Group Description	All participants who received placebo matched to IVA for 8 weeks in treatment period 1 or 2.		All participants who received IVA for 8 weeks in treatment period 1 or 2.
All Cause Mortality
	Placebo		Ivacaftor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Serious Adverse Events
	Placebo		Ivacaftor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/38 (5.3%)		1/38 (2.6%)
Gastrointestinal disorders
Pancreatitis	1/38 (2.6%)		0/38 (0%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	1/38 (2.6%)		0/38 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/38 (0%)		1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Placebo		Ivacaftor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/38 (50%)		12/38 (31.6%)
Gastrointestinal disorders
Aphthous ulcer	2/38 (5.3%)		0/38 (0%)
General disorders
Pyrexia	1/38 (2.6%)		2/38 (5.3%)
Malaise	2/38 (5.3%)		0/38 (0%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	2/38 (5.3%)		5/38 (13.2%)
Upper respiratory tract infection	6/38 (15.8%)		3/38 (7.9%)
Viral upper respiratory tract infection	9/38 (23.7%)		1/38 (2.6%)
Nervous system disorders
Headache	2/38 (5.3%)		1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	2/38 (5.3%)		3/38 (7.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.