A Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02730208
• Collaborator: (none)
• Enrollment: 41
• Locations: 9
• Arms: 2
• Actual Duration (Months): 21.9
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of study is to evaluate the treatment effect of tezacaftor in combination with ivacaftor (TEZ/IVA) on chest imaging endpoints using low-dose computed tomography (LDCT) at Week 72, and to evaluate the safety of TEZ/IVA through Week 72.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Tezacaftor/Ivacaftor; Drug: Ivacaftor; Drug: Placebo; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Placebo-Controlled, Double-blind Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
• Actual Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TEZ/IVA Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks.	Drug: Tezacaftor/Ivacaftor; TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.; Other Names: TEZ/IVA; VX-661/VX-770 ; Drug: Ivacaftor; IVA 150 mg tablet.; Other Names: VX-770; IVA
Placebo Comparator: Placebo Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks.	Drug: Placebo; Placebo matched to TEZ/IVA fixed-dose combination tablet.; Drug: Placebo; Placebo matched to IVA tablet.

Outcome Measures

Primary Outcome Measures

1. Absolute Change in Total Brody/CF-CT Score [From Baseline at Week 72]

   The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease.

Secondary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to Week 76]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Homozygous for the F508del CFTR mutation

• Confirmed diagnosis of CF

• Percent predicted forced expiratory volume (ppFEV1) ≥70% of predicted normal for age, sex, and height during screening.

• Stable CF disease as judged by the investigator

Exclusion Criteria:

• History of any comorbidity 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.

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)

• Pregnant or nursing females.

• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.

• Any contraindication to undergoing chest imaging, as per the site's institutional guidelines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chermside		Australia
2		Melbourne		Australia
3		Nedlands		Australia
4		New Lambton Heights		Australia
5		Parkville SIC		Australia
6		Randwick		Australia
7		South Brisbane		Australia
8		Subiaco		Australia
9		Westmead		Australia

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 26, 2018
• Statistical Analysis Plan - May 7, 2018

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT02730208
• Other Study ID Numbers: VX15-661-112
• First Posted: Apr 6, 2016
• Last Update Posted: Oct 23, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor

Study Results

Participant Flow

Pre-assignment Detail	A total of 41 participants were randomized and treated in the study.

Arm/Group Title	TEZ/IVA	Placebo
Arm/Group Description	Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks.	Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks.
Period Title: Overall Study
STARTED	20	21
COMPLETED	20	20
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	TEZ/IVA	Placebo	Total
Arm/Group Description	Participants received TEZ 100 mg/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks.	Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks.	Total of all reporting groups
Overall Participants	20	21	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.4 (7.5)	20.1 (9.3)	20.2 (8.4)
Sex: Female, Male (Count of Participants)
Female	11 55%	10 47.6%	21 51.2%
Male	9 45%	11 52.4%	20 48.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	20 100%	21 100%	41 100%
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	20 100%	21 100%	41 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Total Brody/Cystic Fibrosis - Computed Tomography (CF-CT) Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	38.29 (22.91)	43.68 (33.96)	40.98 (28.72)

Outcome Measures

1. Primary Outcome

Title	Absolute Change in Total Brody/CF-CT Score
Description	The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease.
Time Frame	From Baseline at Week 72

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received at least 1 dose of study drug.

Arm/Group Title	TEZ/IVA	Placebo
Arm/Group Description	Participants received TEZ 100 mg/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks.	Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks.
Measure Participants	20	21
Least Squares Mean (Standard Error) [scores on a scale]	0.90 (2.09)	2.38 (2.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TEZ/IVA, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Treatment effect outcomes are estimates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95%; -7.47 to 4.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Day 1 up to Week 76

Outcome Measure Data

Analysis Population Description

Safety set included all participants who received at least 1 dose of study drug.

Arm/Group Title	TEZ/IVA	Placebo
Arm/Group Description	Participants received TEZ 100 mg/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks.	Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks.
Measure Participants	20	21
Participants with AEs	20 100%	21 100%
Participants with SAEs	8 40%	13 61.9%

Adverse Events

Time Frame	Day 1 up to Week 76
Arm/Group Title	TEZ/IVA		Placebo
Arm/Group Description	Participants received TEZ 100 mg/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks.		Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks.
All Cause Mortality
	TEZ/IVA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/21 (0%)
Serious Adverse Events
	TEZ/IVA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/20 (40%)		13/21 (61.9%)
Cardiac disorders
Atrioventricular block first degree	1/20 (5%)		0/21 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/20 (5%)		0/21 (0%)
Abdominal pain	0/20 (0%)		1/21 (4.8%)
Vomiting	0/20 (0%)		1/21 (4.8%)
Hepatobiliary disorders
Hepatic cirrhosis	0/20 (0%)		1/21 (4.8%)
Immune system disorders
Type I hypersensitivity	0/20 (0%)		1/21 (4.8%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	5/20 (25%)		6/21 (28.6%)
Lung infection pseudomonal	2/20 (10%)		0/21 (0%)
Atypical mycobacterial lower respiratory tract infection	0/20 (0%)		1/21 (4.8%)
Gastroenteritis	0/20 (0%)		1/21 (4.8%)
Investigations
Bacterial test positive	0/20 (0%)		1/21 (4.8%)
Weight decreased	0/20 (0%)		1/21 (4.8%)
Metabolism and nutrition disorders
Hyperglycaemia	0/20 (0%)		1/21 (4.8%)
Reproductive system and breast disorders
Testicular torsion	1/20 (5%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/20 (0%)		1/21 (4.8%)
Haemoptysis	0/20 (0%)		1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	TEZ/IVA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/20 (95%)		20/21 (95.2%)
Gastrointestinal disorders
Abdominal pain	1/20 (5%)		2/21 (9.5%)
Constipation	0/20 (0%)		2/21 (9.5%)
Nausea	0/20 (0%)		4/21 (19%)
Vomiting	0/20 (0%)		3/21 (14.3%)
General disorders
Pyrexia	3/20 (15%)		2/21 (9.5%)
Fatigue	1/20 (5%)		2/21 (9.5%)
Chest pain	0/20 (0%)		2/21 (9.5%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	5/20 (25%)		9/21 (42.9%)
Upper respiratory tract infection	4/20 (20%)		2/21 (9.5%)
Lower respiratory tract infection bacterial	3/20 (15%)		2/21 (9.5%)
Nasopharyngitis	3/20 (15%)		1/21 (4.8%)
Gastroenteritis	2/20 (10%)		0/21 (0%)
Influenza	2/20 (10%)		1/21 (4.8%)
Pharyngitis	2/20 (10%)		0/21 (0%)
Rhinitis	0/20 (0%)		2/21 (9.5%)
Injury, poisoning and procedural complications
Sunburn	1/20 (5%)		3/21 (14.3%)
Arthropod bite	0/20 (0%)		2/21 (9.5%)
Investigations
Fungal test positive	1/20 (5%)		2/21 (9.5%)
Bacterial test positive	0/20 (0%)		5/21 (23.8%)
Blood alkaline phosphatase increased	0/20 (0%)		2/21 (9.5%)
Nervous system disorders
Migraine	2/20 (10%)		0/21 (0%)
Headache	1/20 (5%)		4/21 (19%)
Respiratory, thoracic and mediastinal disorders
Cough	8/20 (40%)		9/21 (42.9%)
Haemoptysis	4/20 (20%)		2/21 (9.5%)
Productive cough	4/20 (20%)		4/21 (19%)
Oropharyngeal pain	2/20 (10%)		2/21 (9.5%)
Sputum increased	2/20 (10%)		1/21 (4.8%)
Rhinorrhoea	1/20 (5%)		2/21 (9.5%)
Upper respiratory tract congestion	1/20 (5%)		2/21 (9.5%)
Epistaxis	0/20 (0%)		2/21 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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