Clinical Trials Register

Summary
EudraCT Number:	2014-004827-29
Sponsor's Protocol Code Number:	VX14-661-110
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-09-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2014-004827-29

A.3

Full title of the trial

A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long term Treatment With VX 661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del CFTR Mutation

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to assess the efficacy and safety of a combination of two experimental drugs in people with cystic fibrosis (a rare hereditary lung disease)

A.4.1

Sponsor's protocol code number

VX14-661-110

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/098/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Vertex Pharmaceuticals Incorporated
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Vertex Pharmaceuticals Incorporated
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Vertex Pharmaceuticals Incorporated
B.5.2	Functional name of contact point	Clinical Trials and Medical Info
B.5.3	Address:
B.5.3.1	Street Address	50 Northern Avenue
B.5.3.2	Town/ city	Boston
B.5.3.3	Post code	MA 02210
B.5.3.4	Country	United States
B.5.4	Telephone number	001877634 8789
B.5.5	Fax number	001510595 8183
B.5.6	E-mail	medicalinfo@vrtx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/14/1281
D.3 Description of the IMP
D.3.1	Product name	VX-661/ivacaftor (VX-770) 100mg/150 mg
D.3.2	Product code	VX-661/VX-770
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IVACAFTOR
D.3.9.1	CAS number	873054-44-5
D.3.9.2	Current sponsor code	VX-770
D.3.9.4	EV Substance Code	SUB33103
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet assigned
D.3.9.1	CAS number	1152311-62-0
D.3.9.2	Current sponsor code	VX-661
D.3.9.3	Other descriptive name	VRT-893661
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Kalydeco
D.2.1.1.2	Name of the Marketing Authorisation holder	Vertex Pharmaceuticals (U.K.) Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/556
D.3 Description of the IMP
D.3.1	Product name	Ivacaftor
D.3.2	Product code	VX-770, VRT-813077
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IVACAFTOR
D.3.9.1	CAS number	873054-44-5
D.3.9.2	Current sponsor code	VX-770
D.3.9.4	EV Substance Code	SUB33103
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cystic Fibrosis

E.1.1.1

Medical condition in easily understood language

Cystic Fibrosis

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A
To evaluate the long-term safety and tolerability of VX-661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation who are in the Treatment Cohort.

E.2.2

Secondary objectives of the trial

Part A
Treatment Cohort
To evaluate the long-term efficacy of VX-661 in combination with ivacaftor for subjects in the Treatment Cohort.

Observational Cohort
To evaluate the post-treatment safety of VX-661 in combination with ivacaftor for subjects in the Observational Cohort.

Part B
To evaluate the long-term safety, tolerability, and efficacy of VX 661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part A
Subjects entering the Treatment Cohort must meet all of the following criteria:
• Elect to enroll in the Treatment Cohort.
• Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109), study drug treatment and the Safety Follow up Visit for subjects from Study 111 or study drug treatment and follow-up as specified in other Vertex studies investigating VX-661 in combination with ivacaftor
• Willing to remain on a stable CF medication (and supplement) regimen through the Safety Follow-up Visit.

Subjects re-enrolling in the treatment cohort must meet all the following criteria:
• Previously received at least 4 weeks of study drug before discontinuing Study 110 to participate in another qualified Vertex study
• Completed the last required visit of another qualified Vertex study before or during the returning visit in Part A in Study 110
• Willing to remain on a stable CF medication (and supplement) regimen through the Safety Follow-up Visit of Part A
• Subjects who discontinue Study 110 more than once to participate in another qualified Vertex study may not re-enroll in Part A a second time

Subjects entering the Part A Observational Cohort must meet the following criteria:
• <18 years of age (age on the date of informed consent/assent in the parent study)
• Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109), study drug treatment and the Safety Follow up Visit for subjects from Study 111 or study drug treatment and follow-up as specified in other Vertex studies investigating VX-661 in combination with ivacaftor, but do not elect to enroll in the Study 110 Treatment Cohort;
or
• Received at least 4 weeks of study drug treatment in a parent study, but do not meet eligibility criteria for enrollment into the Part A Treatment Cohort.

Part B
• Completed study drug treatment during the Treatment Period in Part A of VX14 661 110, Studies VX15 661 112 or VX16 661 114, or other eligible Vertex studies
• For subjects in the middle of an approved study drug interruption at the end of the Parent study or Part A, or who re-started study drug after an interruption <4 weeks before the end of the Parent study or Part A, criteria for study drug resumption must be met and safety monitoring following resumption or rechallenge must be performed
• Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit

Subjects re enrolling in Part B must meet all of the following criteria
• Previously received at least 4 weeks of study drug before discontinuing Study VX14 661 110 to participate in another qualified Vertex study
• Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B
• Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B.

E.4

Principal exclusion criteria

Part A Treatment Cohort:
• 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.
• Pregnant and nursing females. Females of childbearing potential must have a negative urine pregnancy test at the Day 1 Visit (and at Returning Visit for subjects who re-enroll) and before receiving the first dose of study drug.
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
• History of drug intolerance in the parent study or other qualified Vertex Study that would pose an additional risk to the subject.
• History of poor compliance with study drug and/or procedures in the parent study or other qualified Vertex Study as deemed by the investigator.
• Participation in an investigational drug trial other than Studies 103, 106, 107, 108, 109, 111, other Vertex studies investigating VX-661 in combination with ivacaftor, or other qualified study, or use of a commercially available CFTR modulator (e.g., Kalydeco).
• Previous re-enrollment in the Part A Treatment Cohort of Study 110, after participating in other qualified Vertex studies.

Part B
• 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.
• Pregnant and nursing females
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
• Subjects who permanently discontinue study drug treatment during the parent study or Part A
• History of drug intolerance in the parent study, Part A of study VX14-661-110, or other qualified Vertex study that would pose an additional risk to the subject in the opinion of investigator or Vertex
• History of poor compliance with study drug and/or procedures in the parent study, Part A of Study VX14-661-110, or other qualified Vertex study as deemed by the investigator
• Participation in an investigational drug trial (other than Studies VX13 661 103, VX14 661 106, VX14 661 107, VX14 661 108, VX14 661 109, VX14 661 111, VX15 661 112, VX16 661 114, Part A of Study VX14-661-110, or other eligible Vertex studies investigating VX 661 in combination with ivacaftor) or use of a commercially available CFTR modulator (e.g., Kalydeco)
• Discontinued Study VX14 661 110 (either Part A or Part B) more than once to participate in another qualified Vertex study.

E.5 End points

E.5.1

Primary end point(s)

Part A
Treatment Cohort:
Safety and tolerability of long-term treatment of VX-661 in combination with ivacaftor based on adverse events (AEs), ophthalmologic examinations (subjects <18 years of age, clinical laboratory values (serum chemistry, hematology, coagulation, lipids, vitamins, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry

E.5.1.1

Timepoint(s) of evaluation of this end point

96 weeks

E.5.2

Secondary end point(s)

Part A
Treatment Cohort:
• Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1)
• Relative change from baseline in ppFEV1
• Number of pulmonary exacerbations
• Absolute change from baseline in body mass index (BMI)
• Absolute change from baseline in BMI z score for subjects aged <20 years
• Absolute change from baseline in Cystic Fibrosis Questionnaire–Revised (CFQ R) respiratory domain score
• Absolute change from baseline in body weight
• Absolute change from baseline in body weight z-score for subjects aged <20 years
• Absolute change from baseline in height z-score for subjects aged <20 years
• Time to first pulmonary exacerbation,
• Pharmacokinetic (PK) parameters of VX 661, a VX-661 metabolite (M1 661), ivacaftor, and an ivacaftor metabolite (M1 ivacaftor)

For the Observational Cohort:
• Safety, as determined by related serious adverse events (SAEs)

Part B
• AEs
• Ophthalmologic exams (subjects < 18 years of age [age on the date of informed consent/assent in the parent study])
• Serum liver function tests (LFTs)
• Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1)
• Absolute change from baseline in body mass index (BMI)
• Absolute change from baseline in BMI z score for subjects aged <20 years
• Number of pulmonary exacerbations

E.5.2.1

Timepoint(s) of evaluation of this end point

Through 100 weeks (Week 24 for PK endpoint)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Belgium

Canada

Denmark

France

Germany

Ireland

Israel

Italy

Netherlands

Spain

Sweden

Switzerland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

None

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

645

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

645

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

730

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Adolescents aged 12-17 years old are included

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

600

F.4.2.2

In the whole clinical trial

1375

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects will receive normal standard of care for cystic fibrosis after their participation in the trial has ended.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-10-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-12-05

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