ICH GCP - EU Clinical trials Registry - 2016-001955-29 (NO)

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Summary
EudraCT Number:	2016-001955-29
Sponsor's Protocol Code Number:	024PKAN15004
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-04-20
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

A. Protocol Information

A.1

Member State Concerned

Norway - NOMA

A.2

EudraCT number

2016-001955-29

A.3

Full title of the trial

Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), a Phosphopantothenate replacement therapy, in patients with Pantothenate Kinase-associated Neurodegeneration (PKAN): A Randomized, Double-blind, Placebo-Controlled Study with an Open-Label Extension

A.3.1

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

Efficacy, Safety, and Tolerability of Fosmetpantotenate in patients with Pantothenate Kinase-associated Neurodegeneration (PKAN)

A.4.1

Sponsor's protocol code number

024PKAN15004

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	Retrophin, 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	Retrophin, 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	Retrophin Inc.
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	3721 Valley Centre Drive, Suite 200
B.5.3.2	Town/ city	San Diego
B.5.3.3	Post code	CA 92130
B.5.3.4	Country	United States
B.5.4	Telephone number	+1877-659-5518

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/3/16/1612
D.3 Description of the IMP
D.3.1	Product name	Fosmetpantotenate
D.3.2	Product code	RE-024
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	Fosmetpantotenate
D.3.9.1	CAS number	1858268-66-2
D.3.9.2	Current sponsor code	RE-024
D.3.9.3	Other descriptive name	FOSMETPANTOTENATE DRUG SUBSTANCE
D.3.9.4	EV Substance Code	SUB186881
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	75
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive genetic disorder, the most common form of Neurodegeneration with Brain Iron Accumulation (NBIA). It is a progressive, often fatal, neurodegenerative disease.

E.1.1.1

Medical condition in easily understood language

Neurodegenerative disease.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10053643
E.1.2	Term	Neurodegenerative disorder
E.1.2	System Organ Class	10029205 - Nervous system 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

The efficacy objective of this study is to evaluate the efficacy of fosmetpantotenate over 24 weeks in patients with PKAN.
The safety objective of the study is to assess the safety and tolerability of fosmetpantotenate in patients with PKAN.

E.2.2

Secondary objectives of the trial

To determine the PK following multiple doses of fosmetpantotenate in patients with PKAN.
To explore potential biomarkers of disease, along with their potential response to treatment in patients with PKAN.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Additional Exploratory Assessment for Research
A blood sample will be collected at 2-3 different investigational sites
from up to a total of 8 eligible patients (half adult, half pediatric) with
different confirmed mutations in PANK2 to generate peripheral blood
mononuclear cells (PBMCs).
To be eligible to participate, patients must have negative serologic tests
for all tests outlined in Section 15.2.2 in the Clinical Trial Protocol.
Patients will be required to sign a separate consent to participate in this
exploratory sub-study. If a patient discontinues participation in the substudy,
their participation in the main study will not be affected.

E.3

Principal inclusion criteria

- The patient has a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 (PANK2) gene. (if available, the
specific mutation will be recorded)
- The patient has a score of ≥ 6 on the Pantothenate Kinase-associated Neurodegeneration Activities of Daily Living (PKAN-ADL) scale.

E.4

Principal exclusion criteria

- The patient has required regular or intermittent invasive ventilatory support to maintain vital signs within 24 weeks prior to randomization.
- The patient has had a deep brain stimulation (DBS) device implanted within 6 months prior to screening.
- The patient is unable or unwilling to remain on their pre-study dose(s) of allowed concomitant PKAN maintenance medications and therapies (including DBS settings) for the double-blind period of the study.
- The patient has taken deferiprone within 30 days prior to screening.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint
- Change in the score from the PKAN-ADL

Safety Endpoint
- Safety and tolerability

E.5.1.1

Timepoint(s) of evaluation of this end point

For each patient, the change from Baseline in PKAN-ADL scores at Weeks 3, 6, 12, 18, and 24 of the double-blind period will be used for analysis.

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoint
- Change in the score from Part III of the UPDRS

E.5.2.1

Timepoint(s) of evaluation of this end point

Continuous measures recorded at each study visit from Baseline to the end of the 24-week double-blind period.

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

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

Canada

Czech Republic

France

Germany

Italy

Norway

Poland

Spain

United Kingdom

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.8.9.1

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

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)

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

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

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)

None. The investigator is responsible for ensuring consideration has been given to the post-study care of the patient’s medical needs.

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

2017-10-09

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-12-04

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