Clinical Trials Register

Summary
EudraCT Number:	2017-001078-41
Sponsor's Protocol Code Number:	VX13-809-011
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2017-03-27
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2017-001078-41

A.3

Full title of the trial

A Phase 3, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous 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 in people with cystic fibrosis (a rare pulmonary disease) to assess the pharmacokinetics and safety of a combination of two experimental drugs"

A.4.1

Sponsor's protocol code number

VX13-809-011

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01897233

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/220/2016

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, Massachusetts
B.5.3.3	Post code	02210
B.5.3.4	Country	United States
B.5.4	Telephone number	1877634-8789
B.5.5	Fax number	1510595-8183
B.5.6	E-mail	medical_info@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	Yes
D.2.1.1.1	Trade name	lumacaftor/ivacaftor
D.2.1.1.2	Name of the Marketing Authorisation holder	Vertex Pharmaceuticals (Europe) Limited
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	lumacaftor/ivacaftor
D.3.2	Product code	VX-809/VX-770
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Yes
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	LUMACAFTOR
D.3.9.1	CAS number	936727-05-8
D.3.9.2	Current sponsor code	VX-809
D.3.9.3	Other descriptive name	LUMACAFTOR
D.3.9.4	EV Substance Code	SUB130518
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.3.8 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	125
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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10010331
E.1.2	Term	Congenital, familial and genetic disorders
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 PK of multiple doses of lumacaftor in combination with ivacaftor
Part B - To evaluate the safety and tolerability of lumacaftor in combination with ivacaftor through
Week 24

E.2.2

Secondary objectives of the trial

Part A:
- To investigate the PK of a lumacaftor metabolite, M28 (M28-lumacaftor), and ivacaftor
metabolites, M1 and M6 (M1-ivacaftor and M6-ivacaftor)
- To evaluate the safety and tolerability of multiple doses of lumacaftor in combination
with ivacaftor

Part B:
- To evaluate the PD of lumacaftor in combination with ivacaftor through Week 24
- To evaluate the off-drug response after the Washout Period (Week 24 to Week 26)
- To evaluate the PK of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and
M6-ivacaftor for lumacaftor in combination with ivacaftor

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Subjects (males and/or females), 6 through 11 years of age, inclusive, on the date of
informed consent (and assent, if applicable) (Part A and Part B).
•Confirmed diagnosis of CF defined as: with 2 CF-causing mutations, chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
•Subjects who weigh ≥15 kg without shoes at Screening Visit
•Subjects who are homozygous for the F508del-CFTR mutation
•Subjects with percent predicted forced expiratory volume in 1 second (FEV1) of 70% to 105% (inclusive) (Part A) or ≥40% (Part B) at Screening Visit
•Subjects with stable CF disease and who are willing to remain on stable CF medication regimen
•Able to swallow tablets

E.4

Principal exclusion criteria

•History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
•Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 of the study
•Abnormal liver function as defined in the protocol at Screening Visit
•Abnormal renal function as defined in the protocol at Screening Visit
•History of solid organ or hematological transplantation
•Ongoing participation in an investigational drug study or prior participation in an investigational drug study within 30 days prior of Screening Visit
•History or evidence of lens opacity or cataract at Screening Visit
•Colonization with organisms associated with a more rapid decline in pulmonary status at Screening Visit (Part A only)
•A standard 12-lead ECG demonstrating QTcF >450 msec at Screening Visit

E.5 End points

E.5.1

Primary end point(s)

Part A:
Lumacaftor and ivacaftor PK parameters, including maximum observed concentration (Cmax)
and area under the concentration versus time curve from time of dosing to time tau (AUC0-τ)

Part B:
Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values
(serum chemistry, hematology, coagulation studies, and urinalysis), standard 12-lead
electrocardiograms (ECGs), vital signs, pulse oximetry, ophthalmological examinations, and
spirometry

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A:
Day1, Day 14

Part B:
Day 1 up to week 26

E.5.2

Secondary end point(s)

Part A:
- M28-lumacaftor, M1-ivacaftor, and M6-ivacaftor PK parameters, including Cmax and AUC0-τ
- Safety and tolerability of lumacaftor in combination with ivacaftor as determined by AEs,
clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis), standard 12-lead ECGs, vital signs, pulse oximetry, and spirometry

Part B:
- Average absolute change from baseline in sweat chloride at Day 15 and at Week 4
- Absolute change from baseline in body mass index (BMI) and BMI-for-age z-score at Week 24
- PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor
- Absolute change from baseline in weight and weight-for-age z-score at Week 24
- Absolute change from baseline in height and height-for-age z-score at Week 24
- Absolute change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score at Week 24
- Absolute change from baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) domains at Week 24
- Absolute change in sweat chloride from Week 24 at Week 26

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A:
Day 1, Day 1 up to Day 28

Part B:
through week 26

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

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.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Canada

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

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)

No specific plans for additional treatment after the subject has ended the participation in the trial

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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