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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 9 November 2020
Main ID:  EUCTR2015-002379-81-GB
Date of registration: 12/06/2017
Prospective Registration: Yes
Primary sponsor: Pharnext SA
Public title: An International, multi-center, FOLLOW-UP extension study to study the long term safety of PXT3003 in patients with Charcot-Marie-Tooth Disease type 1A.
Scientific title: International, multi-center, open-label FOLLOW-UP extension study assessing the long term safety and tolerability of PXT3003 in patients with Charcot-Marie-Tooth Disease type 1A.
Date of first enrolment: 28/07/2017
Target sample size: 187
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002379-81
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Open Labelled, Parallel Group If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Belgium Canada France Germany Netherlands Spain United Kingdom United States
Contacts
Name: Adrian Hepner   
Address:  46 rue Saint Lazare 75009 Paris France
Telephone: +33(0)141092230
Email: ahepner@pharnext.com
Affiliation:  Pharnext SA
Name: Adrian Hepner   
Address:  46 rue Saint Lazare 75009 Paris France
Telephone: +33(0)141092230
Email: ahepner@pharnext.com
Affiliation:  Pharnext SA
Key inclusion & exclusion criteria
Inclusion criteria:
Period 1
• Patients under P and D1 must have completed 15 months of double-blind treatment in the primary study CLN-PXT3003-02, including all procedures required at the Study Termination visit (V6) or patients under D2 prematurely discontinued from CLN-PXT3003-02 (due to sponsor decision on September 18th, 2017) must have performed an early V6
• Patients who completed the V6 assessments within 4 weeks prior to extension study or patients who have completed a new baseline visit (VB) if the V6 assessments were not completed in the 4 weeks prior to study entry.
• Female patients must agree to continue using an approved method of birth control throughout the extension study.
• Patients must sign a written informed consent, specific to the extension study, in order to participate in this study. For minor patients, both patient’s and parents’ consent shall be collected.

Period 2
• Patients must sign a written informed consent to continue after V9 to access to study treatment.
Are the trial subjects under 18? yes
Number of subjects for this age range: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
Patients with any of the following criteria will be excluded from entry:
1. Presenting any clinically significant change in health status that, in the opinion of the Investigator, would prevent the subject from participating in this study or successfully completing this study.
2. Any unauthorized concomitant treatments, in the 4 weeks preceding study entry, as study CLN-PXT3003-02.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Charcot-Marie-Tooth Disease type 1A
MedDRA version: 20.0 Level: LLT Classification code 10008414 Term: Charcot-Marie-Tooth disease System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Intervention(s)

Product Code: PXT3003 Dose 1
Pharmaceutical Form: Oral solution
INN or Proposed INN: BACLOFEN
CAS Number: 1134-47-0
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.6-
INN or Proposed INN: NALTREXONE
CAS Number: 16676-29-2
Current Sponsor code: NA
Other descriptive name: NALTREXONE HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.07-
INN or Proposed INN: Sorbitol
CAS Number: 50-70-4
Current Sponsor code: NA
Other descriptive name: D-SORBITOL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 21-

Product Code: PXT3003 Dose 2 (equivalent to twice Dose 1)
Pharmaceutical Form: Oral solution
INN or Proposed INN: BACLOFEN
CAS Number: 1134-47-0
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.2-
INN or Proposed INN: NALTREXONE
CAS Number: 16676-29-2
Current Sponsor code: NA
Other descriptive name: NALTREXONE HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.14-
INN or Proposed INN: Sorbitol
CAS Number: 50-70-4
Current Sponsor code: NA
Other descriptive name: D-SORBITOL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 42-

Primary Outcome(s)
Main Objective: Period 1: The main objective of the study is to assess the long-term safety and tolerability of PXT3003 up to 2 years, and to increase the exposed population receiving PXT3003 for at least 9 months.

Period 2: For patients continuing after V9, the main objective will be to offer patients the opportunity to access to twice Dose 1 equivalent to Dose 2 of PXT3003, with a regular safety follow-up.
Primary end point(s): Period 1
To assess the safety and tolerability of PXT3003 in CMT1A patients during a long-term period, the primary endpoint will be the incidence of Treatment-Emergent Adverse Events (TEAEs) Related to the Investigational Product during the follow-up, in patients exposed to PXT3003 for up to 24 months or 9 months.
The incidence of TEAEs in the two groups P / D1-9m and P/ D2-9m will be compared to the first 9-month placebo period in the primary study.
The incidence of TEAEs in the two groups D1-24m, D2-24m will be compared to the first 9-month period in the primary study for their corresponding group.
Period 2
After V9, the incidence of TEAEs related to investigational product will be described.
Secondary Objective: Period 1:
Secondary objectives:
- To gather up-to-2-year data to estimate the long-term effect of PXT3003 on clinical, functional and electrophysiological endpoints;
- To compare the effect of PXT3003 in patients receiving PXT3003 active dose from the start of the primary study to patients assigned to a delayed start (i.e., who received placebo during the primary study) in order to determine if PXT3003 slows the progression of the disease
- To assess the evolution of potential blood biomarkers and molecular changes in skin biopsy on the longer term.
Period 2: For patients continuing after V9, sefty follow-up and ONLS score follow-up on a 6-month frequency.
Timepoint(s) of evaluation of this end point: Period 1: 9 month after the inclusion in the open-label study (either Dose 1 or Dose 2 equivalent to twice Dose 1)

Period2: every 6 months until the end of the study, when 1st marketing authorization for PXT3003 is obtained (estimated in 2024)
Secondary Outcome(s)
Secondary end point(s): PERIOD 1:

• Safety Endpoints:

Other safety endpoints will be assessed:
- Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome;
- Incidence of AE leading to withdrawal of study drug;
- Changes in laboratory parameters, ECGs, vital signs and physical examination

• Efficacy Endpoints:

The clinical response will be assessed by the change over time of the following efficacy endpoints:
- the Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items;
- the Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items;
- the functional assessments measured by Nine-hole Peg Test (9-HPT), Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides), and Time to walk 10 meters;
- electrophysiological parameters assessing sensory and motor responses of ulnar and radial nerves (non-dominant side) including Compound Muscle Action Potential (CMAP) on ulnar nerve; Sensory Nerve Action Potential (SNAP) on radial nerve; and Nerve conduction velocity (NCV);
- the EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D);
- the individualized main impairment in daily activities (defined at baseline with the patient) by self-assessment on visual analog scale.

For the patients receiving up to 24 months of active dose along the two successive studies (from groups D1-24m and D2-24m) the clinical response will be assessed by the change from V1/baseline of each endpoint.

For the patients who received placebo during the 15-month primary study and active drug during the 9-month extension study (from groups P/D1-9m and P/D2-9m) the clinical response will be assessed after 9 months of PXT3003 treatment by the change from V6/baseline.

The Percentage of responders to PXT3003 defined as patients improving on ONLS at end of treatment (V9) will be assessed in the patients receiving the active dose of PXT3003 up to 24 months (from groups D1-24m, D2-24m).

PERIOD 2:

• Safety Endpoints:

After V9,
- the incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome;
- the incidence of related TEAEs
- the incidence of TEAE leading to withdrawal of study drug
- the incidence of Serious TEAE, Related Serious TEAEs and Serious TEAE leading to withdrawal of the study drug
- changes in laboratory parameters, ECGs, vital signs and physical examination

will be described.

• Efficacy Endpoints:

After V9, the Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items shall be assessed every 6 months and the clinical response will be assessed by the change over time of ONLS
Timepoint(s) of evaluation of this end point: Period 1: 9 month after the inclusion in the open-label study (either Dose 1 or Dose 2 equivalent to twice Dose 1)

Period2: every 6 months until the end of the study, when 1st marketing authorization for PXT3003 is obtained (estimated in 2024)
Secondary ID(s)
122505
2015-002379-81-FR
CLN-PXT3003-03
Source(s) of Monetary Support
Pharnext SA
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 28/07/2017
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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