Clinical Trials Register

Summary
EudraCT Number:	2015-003105-41
Sponsor's Protocol Code Number:	PTC124-GD-031-MPS
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-09-08
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

UK - MHRA

A.2

EudraCT number

2015-003105-41

A.3

Full title of the trial

CNS Unmet Medical Need in Mucopolysaccharidosis: A Phase 2 Safety and Pharmacokinetics Study of Ataluren (COMPASS)

A.3.1

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

Treatment for Nonsense Mutation Mucopolysaccharidosis Type I

A.3.2

Name or abbreviated title of the trial where available

COMPASS

A.4.1

Sponsor's protocol code number

PTC124-GD-031-MPS

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PTC Therapeutics Inc.
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	PTC Therapeutics Inc.
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	Medpace Germany GmbH
B.5.2	Functional name of contact point	Medpace Regulatory Submissions
B.5.3	Address:
B.5.3.1	Street Address	Theresienhöhe 30
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	80339
B.5.3.4	Country	Germany
B.5.4	Telephone number	004989895571860
B.5.5	Fax number	0049898955718160
B.5.6	E-mail	regsubmissions@medpace.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	EMA/OD/135/14
D.3 Description of the IMP
D.3.1	Product name	ataluren
D.3.2	Product code	PTC124
D.3.4	Pharmaceutical form	Powder for oral suspension
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	ATALUREN
D.3.9.1	CAS number	775304-57-9
D.3.9.2	Current sponsor code	PTC124
D.3.9.4	EV Substance Code	SUB89249
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.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	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	EMA/OD/135/14
D.3 Description of the IMP
D.3.1	Product name	ataluren
D.3.2	Product code	PTC124
D.3.4	Pharmaceutical form	Powder for oral suspension
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	ATALUREN
D.3.9.1	CAS number	775304-57-9
D.3.9.2	Current sponsor code	PTC124
D.3.9.4	EV Substance Code	SUB89249
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	250
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: 3
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	EMA/OD/135/14
D.3 Description of the IMP
D.3.1	Product name	ataluren
D.3.2	Product code	PTC124
D.3.4	Pharmaceutical form	Powder for oral suspension
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	ATALUREN
D.3.9.1	CAS number	775304-57-9
D.3.9.2	Current sponsor code	PTC124
D.3.9.4	EV Substance Code	SUB89249
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	1000
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

Nonsense mutation Mucopolysaccharidosis Type I

E.1.1.1

Medical condition in easily understood language

Mucopolysaccharidosis I

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10056886
E.1.2	Term	Mucopolysaccharidosis I
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

- Characterize the safety profile of ataluren in patients with nmMPS I
- Evaluate the CSF and plasma PK of ataluren in patients with nmMPS I

E.2.2

Secondary objectives of the trial

• Evaluate CSF GAG levels in patients with nmMPS I following ataluren treatment
• Evaluate urinary GAG levels in patients with nmMPS I, following ataluren treatment
• Evaluate plasma GAG levels in patients with nmMPS I following ataluren treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Evidence of signed and dated informed consent document(s) indicating that the study candidate (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible institutional review board/independent ethics committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the patient should be followed.
2.Age ≥2 years.
3.Clinical diagnosis of MPS I, confirmed by measurable clinical signs and symptoms of MPS I and a fibroblast or leukocyte α-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory, with clinically stable disease.
4.Documentation of the presence of a nonsense mutation in at least 1 allele of the α-L-iduronidase (IDUA) gene.
5.Verification that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the IDUA gene.
6.Confirmed screening laboratory values within the central laboratory ranges
7. In patients who are sexually active, willingness, if not surgically sterile, to abstain from
sexual intercourse or employ a barrier or medical method of contraception during ataluren
administration and for 60 days after the last ataluren administration.
8. Willingness and ability to comply with scheduled visits, drug administration plan, study
procedures (including lumbar punctures), and study restrictions.

E.4

Principal exclusion criteria

1. Any change (initiation, change in type of drug, dose modification [not weight based], schedule modification, interruption, discontinuation, or re-initiation) in ERT within 6 months prior to start of screening.
2. Exposure to another investigational drug or (intrathecal/spinal) device within 3 months prior to enrollment.
3. Ongoing participation in any other therapeutic clinical trial.
4.The patient is unable to have a lumbar puncture performed due to severe musculoskeletal/spinal abnormalities, risk of abnormal bleeding, or the presence of a ventriculoperitoneal shunt.
5. The patient is unable to provide a CSF sample due to an opening CSF pressure that exceeds 30.0 cm H2O.
6. The patient has any known or suspected hypersensitivity to anesthesia that is thought to be by a physician or anesthesiologist as an unacceptably high risk for anesthesia due to compromised airways or other conditions.
7. Is pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test [β-human chronic gonadotropin (hCG)] at screening.
8. Ongoing use of the following drugs:
Drugs metabolized by CYP2C8 (eg, paclitaxel) or CYP2C9 (eg, coumarin anticoagulants [warfarin], phenytoin or tolbutamide)
Drugs that are inhibitors of breast cancer resistant protein (BCRP) (eg, cyclosporine, eltrombopag, geftinib). Note: Topical cyclosporine therapy is permitted.
Drugs that are substrates of UGT1A9 (eg, propofol, mycophenolate mofetil), OAT1, OAT3, or OATP1B3 (eg, oseltamivir, acyclovir, captopril, furosemide, bumetanide, valsartan, pravastatin, rosuvastatin, atorvastatin, pitavastatin)
Drugs that are general inhibitors of UGT (eg, probenecid, valproic acid)
9. Ongoing IV aminoglycoside use.
10. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the patient, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results.
11. Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate).
12. Surgery within 30 days prior to enrollment, or anticipated surgery during study participation

E.5 End points

E.5.1

Primary end point(s)

• Overall safety profile of ataluren characterized by type, frequency, severity, timing, and relationship to study drug of any adverse events;
new physical examination, laboratory test, or electrocardiogram (ECG) abnormalities; drug discontinuations due to adverse events; and serious adverse events (SAEs)
• Ataluren CSF concentrations as assessed by a validated bioanalytical method
• Ataluren plasma concentrations before and 2, 4, and 6 hours after morning drug administration at Day 1 and every 6 weeks during treatment, as assessed by a validated bioanalytical method.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety: Every visit
CSF PK: Day 1, 85
Plasma PK: Day 1, 43, 85, and 113

E.5.2

Secondary end point(s)

- Change in CSF GAG levels from pretreatment to end of treatment
- Change in urinary GAG levels from pretreatment to end of treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

Urinary GAG Levels: Every visit
Plasma GAG Levels: Screening, and Days 1, 43, 85, 113, and End of Treatment F/U

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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.8.9.1

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

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

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

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

minors

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

After participation in the trial, the decision on patient treatment will be at the discretion of the patient's primary physician.

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

2015-10-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-03-09

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