Clinical Trials Register

Summary
EudraCT Number:	2016-001004-33
Sponsor's Protocol Code Number:	VX15-809-115
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-01-10
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

2016-001004-33

A.3

Full title of the trial

A Phase 3, 2-Part, Open-label Study to Evaluate the Safety and Pharmacokinetics of Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Through 5 Years 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

Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

A.4.1

Sponsor's protocol code number

VX15-809-115

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02797132

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/198/2017

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	18776348789
B.5.5	Fax number	15105958183
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	No
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	Granules in sachet
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.3.9.4	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.3.8 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.3.9.4	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	150
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	188
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 LUM and IVA and their metabolites
Part B: to evaluate the safety of LUM/IVA

E.2.2

Secondary objectives of the trial

Part A: To evaluate the safety of LUM/IVA
Part B: To evaluate the PD of LUM/IVA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit
- Subjects with confirmed diagnosis of CF at the Screening Visit
- Subjects who are homozygous for the F508del Cystic fibrosis transmembrane conductance regulator (CFTR) mutation

E.4

Principal exclusion criteria

- Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for 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
- A standard 12 lead ECG demonstrating QTc >450 millisecond (msec) at the Screening Visit.
- History of solid organ or hematological transplantation.
- Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within
30 days of the Screening Visit.
- History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a
licensed ophthalmologist during the ophthalmologic examination at the Screening Visit

E.5 End points

E.5.1

Primary end point(s)

- Part A: Pharmacokinetic (PK) parameters of lumacaftor (LUM) and ivacaftor (IVA): estimated peak concentrations
(Cmax)
- Part A: Pharmacokinetic (PK) parameters of lumacaftor (LUM) and ivacaftor (IVA): estimated trough concentrations
(Ctrough)
- Part B: Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and
serious adverse events (SAEs)

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A: up to 15 Days
Part B: Baseline up to 28 days after last dose (up to 28 weeks)

E.5.2

Secondary end point(s)

- Part A: PK parameters of LUM and IVA metabolites: estimated peak concentrations (Cmax) of lumacaftor and ivacaftor metabolites
- Part A: PK parameters of LUM and IVA metabolites: estimated trough concentrations (Ctrough) of lumacaftor and ivacaftor metabolites
- Part A: Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
- Part B: Absolute change from baseline in sweat chloride level
- Part B: Absolute change from baseline in body mass index (BMI) and BMI for age z score

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A: up to 15 days
Part A (safety): up to 10 +/- 3 days after the last dose (up to 25 +/- 3 days)
Part B: Week 24

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.8.3

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

Yes

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children aged 2-5 years old

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)

All subjects who complete 24 weeks of study drug treatment will be eligible to enroll in the Treatment Cohort or Observational Cohort of an extension study.

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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