Clinical Trials Register

Summary
EudraCT Number:	2015-002378-19
Sponsor's Protocol Code Number:	CLN-PXT3003-02
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-07-27
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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2015-002378-19

A.3

Full title of the trial

International, multi-center, randomized, double-blind, placebo-controlled phase III study assessing in parallel groups the efficacy and safety of 2 doses of PXT3003 in patients with Charcot-Marie-Tooth Disease type 1A treated 15 months

Etude de phase III, internationale, multicentrique, randomisée, en double aveugle, contre placebo, visant à évaluer en groupes parallèles l’efficacité et la sécurité d’emploi de 2 doses du PXT3003 chez les patients atteints d’une maladie de Charcot Marie Tooth de type IA traités 15 mois.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

PLEO-CMT

A.4.1

Sponsor's protocol code number

CLN-PXT3003-02

A.5.4

Other Identifiers

Name:

US IND

Number:

122505

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	PHARNEXT
B.1.3.4	Country	France
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	Pharnext
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PHARNEXT
B.5.2	Functional name of contact point	Catherine Scart-Grès
B.5.3	Address:
B.5.3.1	Street Address	11 rue des peupliers
B.5.3.2	Town/ city	Issy les Moulineaux
B.5.3.3	Post code	92130
B.5.3.4	Country	France
B.5.4	Telephone number	+330141092230
B.5.5	Fax number	+330141092231
B.5.6	E-mail	c.scart-gres@pharnext.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/3/14/1260
D.3 Description of the IMP
D.3.2	Product code	PXT3003 dose 1
D.3.4	Pharmaceutical form	Oral solution
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	RS-BACLOFEN
D.3.9.1	CAS number	1134-47-0
D.3.9.4	EV Substance Code	SUB05667MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NALTREXONE HYDROCHLORIDE
D.3.9.1	CAS number	16676-29-2
D.3.9.3	Other descriptive name	NALTREXONE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB14629MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.07
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	D-SORBITOL
D.3.9.1	CAS number	50-70-4
D.3.9.3	Other descriptive name	D-SORBITOL
D.3.9.4	EV Substance Code	SUB20837
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	21
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	EU/3/14/1260
D.3 Description of the IMP
D.3.2	Product code	PXT3003 dose 2
D.3.4	Pharmaceutical form	Oral solution
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	RS-BACLOFEN
D.3.9.1	CAS number	1134-47-0
D.3.9.4	EV Substance Code	SUB05667MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NALTREXONE HYDROCHLORIDE
D.3.9.1	CAS number	16676-29-2
D.3.9.3	Other descriptive name	NALTREXONE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB14629MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.14
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	D-SORBITOL
D.3.9.1	CAS number	50-70-4
D.3.9.3	Other descriptive name	D-SORBITOL
D.3.9.4	EV Substance Code	SUB20837
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	42
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	Oral solution
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

Charcot-Marie-Tooth Disease - Type 1A

E.1.1.1

Medical condition in easily understood language

Charcot-Marie-Tooth Disease - Type 1A

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10008414
E.1.2	Term	Charcot-Marie-Tooth disease
E.1.2	System Organ Class	100000004850

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

To assess the efficacy of PXT3003 compared to Placebo on the disability measured by the ONLS score in CMT1A patients treated for 15 months.

E.2.2

Secondary objectives of the trial

- To assess the efficacy of PXT3003 compared to Placebo on clinical score and functional tests, electrophysiological parameters, and measures of quality of life;
- To assess the safety and tolerability of PXT3003 compared to Placebo;
- To assess plasma concentrations of PXT3003 components (at peak and trough) when administered with 2 different doses;
- To assess the change over time of potential blood biomarkers;
- To assess molecular changes in skin biopsy, when this procedure will be possible (ancillary sub-study);
- To explore potential new imaging biomarkers by calf MRI, when this procedure will be possible (ancillary sub-study).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, aged from 16 to 65 years;
2. Patient with a proven genetic diagnosis of CMT1A;
3. Mild-to-moderate severity assessed by CMTNS-v2 with a score >2 and ≤18;
4. Muscle weakness in at least foot dorsiflexion;
5. Motor nerve conduction of the ulnar nerve of at least 15m/sec;
6. Providing signed written informed consent to participate in the study and willing and able to comply with all study procedures and scheduled visits.

E.4

Principal exclusion criteria

1. Any other associated cause of peripheral neuropathy such as diabetes;
2. Patients with another significant neurological disease or a concomitant major systemic disease;
3. Clinically significant history of unstable medical illness since the last 30 days (unstable angina, cancer…) that may jeopardize the participation in the study;
4. Significant hematologic disease, hepatitis or liver failure, renal failure;
5. Limb surgery within six months before randomization or planned before trial completion;
6. Clinically significant abnormalities on the pre-study laboratory evaluation, physical evaluation, electrocardiogram (ECG);
7. Elevated ASAT/ALAT (> 3 x ULN) and elevated serum creatinine levels (> 1.25 x ULN);
8. History of recent alcohol or drug abuse or non-adherence with treatment or other experimental protocols;
9. Patients using unauthorized concomitant treatments including but not limited to baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, levothyroxin and potentially neurotoxic drugs such as amiodarone, chloroquine, canti-ancer drugs susceptible to induce a peripheral neuropathy; (list provided in appendix 1). Patients who can/agree to stop these medications 4 weeks before randomization and during the whole study duration can be included;
10. Female of childbearing potential (apart of patients using adequate contraceptive measures), pregnant or breast feeding;
11. Known hypersensitivity to any of the individual components of PXT3003;
12. Porphyria as it is a contra indication to baclofen, and it may also induce neuropathy;
13. Suspected inability to complete the study follow-up (foreign workers, transient visitors, tourists or any others for whom follow-up evaluation is not assured);
14. Limited mental capacity or psychiatric disease rendering the subject unable to provide written informed consent or comply with evaluation procedures;
15. Patients who have participated in another trial of investigational drug(s) within the past 30 days;
16. If a patient from the same family, living in the same household, has already been included in this study, it will not be possible to include another patient from the same family to avoid mixing of therapeutic units; therefore there would be a risk of inversion of the blind treatments which could jeopardize the interpretation of study results.

E.5 End points

E.5.1

Primary end point(s)

Overall Neuropathy Limitation Scale (ONLS) score measuring the disability.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline (V1) ; 12 and 15 months of treatment (V5 and V6)

E.5.2

Secondary end point(s)

- Responders Rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment;
- Arm and leg sub-items of ONLS;
- Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS-v2), including its sub-items;
- Nine-hole Peg Test (9-HPT) performed on non-dominant hand;
- Quantified Muscular Testing (QMT) by Hand grip and Foot dorsiflexion dynamometry (mean of both sides);
- Time to walk 10 meters;
- Electrophysiological parameters assessing sensory and motor responses of ulnar and radial nerves (non-dominant side) including:
o Compound Muscle Action Potential (CMAP) on ulnar nerve;
o Sensory Nerve Action Potential (SNAP) on radial nerve;
o Nerve conduction velocity (NCV);
- Quality of life measured by:
o EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D);
o VAS on self-assessment of the individualized main impairment in daily activities defined at baseline with the patient.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline ; after 6 months of treatment (V3); after 12 months of treatment (V5); after 15 months of treatment (V6)

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

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)

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

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

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

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)

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:

270

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

200

F.4.2.2

In the whole clinical trial

300

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)

In order to stimulate the recruitment and motivate patients to be
enrolled, patients having completed the 15-month study will be eligible
to receive PXT3003 in a follow-up extension trial for 9 months if they
are willing to continue the treatment. They will be attributed to active
drug by a second randomization. This 9-month extension study will
provide additional long-term data on safety and additional efficacy data
that could provide some evidence of disease modifying effect.

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

2015-08-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-03-22

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials