Assessing Long Term Safety and Tolerability of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A

NCT ID: NCT03023540

Last Updated: 2024-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

187 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-07

Study Completion Date

2024-12-31

Brief Summary

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All randomised patients with Charcot-Marie-Tooth Type 1A (CMT1A) who completed the primary study CLN-PXT3003-02, i.e. treatment with PXT3003 or placebo, are eligible to continue in the extension study CLN-PXT3003-03.

Period 1: Patients randomised to PXT3003 dose 1 or placebo in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 1 (5 mL). Patients randomised to PXT3003 dose 2 (5 mL) in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 2 or PXT3003 twice dose 1 (2x5 mL).

Period 2: All patients continue on twice dose 1 (2X5mL).

Detailed Description

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PXT3003 is a rational design, fixed combination of low-dose (RS) baclofen, naltrexone hydrochloride and D-sorbitol. The use of PXT3003 in a multicenter, randomised, placebo controlled phase II study (CLN-PXT3003-01) was well-tolerated and safe in patients with CMT1A for the three dose-levels investigated (Attarian et al., 2014). The intermediate and high dose of PXT3003 demonstrated an improvement of disability in this patient population.

Subsequently a multicenter, randomised, placebo controlled phase III study (CLN-PXT3003-02) to assess the efficacy and safety of PXT3003 in the treatment of patients with CMT1A was initiated in December 2015. In March 2017 the first patients completed the 15-month treatment with PXT3003 and rolled over into the extension study CLN-PXT3003-03.

During Period 1 (9 months), patients that were randomised to PXT3003 dose 1 or placebo in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 1 (5 mL). Patients randomised to PXT3003 dose 2 (5 mL) in the primary study (CLN-PXT3003-02) continued in the extension study on on PXT3003 dose 2 or PXT3003 twice dose 1 (2x5 mL). During Period 2, all patients continue on twice dose 1 (2X5mL).

Conditions

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Charcot-Marie-Tooth Disease, Type IA

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Patients who completed the pivotal phase III study CLN-PXT3003-02 are allowed to continue in this open-label study. In Period 1, patients who were randomly assigned to placebo or low-dose PXT3003 in pivotal phase III study were assigned to receive low-dose PXT3003 (5 mL), whereas patients assigned to high-dose PXT3003 continued on that dose (receiving the high-dose PXT3003 (5 mL) or twice the low-dose for each administration (i.e. 10 mL)). The primary objective was to assess safety and tolerability for prolonged exposure to PXT3003, and to evaluate the effect on disability in patients with mild to moderate CMT1A.

In Period 2, all patients are allowed to continue in an open-label fashion to receive high-dose PXT3003 (receiving twice the low-dose for each administration (i.e. 10 mL). The objective is to mainly assess the safety and tolerability in the aforementioned patient population.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PXT3003 dose 1

Period 1, PXT3003 : Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months

Group Type ACTIVE_COMPARATOR

PXT3003

Intervention Type DRUG

Liquid oral solution, twice 5 mL (Dose 1) bid

PXT3003 dose 2

Period 1, PXT3003: Liquid oral solution (1.2 mg/mL baclofen, 0.14 mg/mL naltrexone HCl and 420 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months

Period 2, PXT3003: Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 10 mL bid (taken morning and evening with food)

Group Type ACTIVE_COMPARATOR

PXT3003

Intervention Type DRUG

Liquid oral solution, twice 5 mL (Dose 1) bid

Interventions

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PXT3003

Liquid oral solution, twice 5 mL (Dose 1) bid

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients previously randomized to study CLN-PXT3003-02 under placebo and dose 1 and having completed 15 months of double-blind treatment in that study, including all procedures required at the Study Termination visit (V6) or
* Patients previously randomized to the initial study CLN-PXT3003-02 under dose 2, prematurely discontinued following sponsor decision, and having performed all procedures required at the Study Termination visit (V6)
* Patients whose V6 was performed within 4 weeks before entering the extension study or if not done must have a new baseline visit (VB)
* 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. In case of minor children aged 16 to 18 years, both parent' and children's consents should be collected


* Patients 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)
* 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. In case of minor children aged 16 to 18 years, both parent' and children's consents should be collected

Exclusion Criteria

* 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
* Any unauthorized concomitant treatments, as study CLN-PXT3003-02 (e.g. including but not limited to baclofen, naltrexone,sorbitol (pharmaceutical form), opioids, levothyroxin, and potentially neurotoxic drugs such as amiodarone, chloroquine, cancer drugs susceptible to induce peripheral neuropathy)
Minimum Eligible Age

17 Years

Maximum Eligible Age

67 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Synteract HCR (Syneos Health)

UNKNOWN

Sponsor Role collaborator

Premier Research Group plc

UNKNOWN

Sponsor Role collaborator

Greenphire

UNKNOWN

Sponsor Role collaborator

Theradis

UNKNOWN

Sponsor Role collaborator

Amarex

UNKNOWN

Sponsor Role collaborator

Eurofins Optimed

INDUSTRY

Sponsor Role collaborator

Pharnext S.C.A.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shahram Attarian, MD

Role: PRINCIPAL_INVESTIGATOR

CHU la Timone, Marseille, France

Teresa Sevilla, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario i Politécnico La F, Valencia, Spain

Marianne de Visser, MD

Role: PRINCIPAL_INVESTIGATOR

Academic Medical Center, Amsterdam, Netherlands

Mark Roberts, MD

Role: PRINCIPAL_INVESTIGATOR

Selor Royal NHS Foundation Trust, Manchester, UK

Florian Thomas, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Seton Hall-Hackensack-Meridian School of Medicine, Hackensack, USA

Locations

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Department of Neurology, Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Department of Neurology, McKnight Brain Institute

Gainesville, Florida, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Department of Neurology, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Department of Neurology and Psichiatry, Saint Louis University

St Louis, Missouri, United States

Site Status

Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center

New York, New York, United States

Site Status

Saint Luke's Rehabilitation Institute

Spokane, Washington, United States

Site Status

Departement of Neurology, UZ Leuven

Leuven, , Belgium

Site Status

University Hospital of Quebec

Québec, Quebec, Canada

Site Status

Cntre de Reference des Maladies Neuromusculaires, Hopital Swynghedauwl, CHU Lille

Lille, , France

Site Status

Centre de Reference des Neuropathies Peripheriques Rare, Hopital Dupuytren, CHU Limoges

Limoges, , France

Site Status

Service de Neurologie et du Sommeil, CHU Lyon Sud

Lyon, , France

Site Status

Centre de Reference des Maladie Neuromusculaires, CHU la Timone

Marseille, , France

Site Status

Centre de Reference des Maladie Neuromusculaires, Hotel Dieu, CHU de Nantes

Nantes, , France

Site Status

Service de Neurologie, Hopital Kremlin Bicetre

Paris, , France

Site Status

Departement of Neurology, Academic Medical Center

Amsterdam, , Netherlands

Site Status

Department of neurology, Hospital Univesitario de Bellvitge

Barcelona, , Spain

Site Status

Servicio de Neurologia, Hospital Universitario La Paz

Madrid, , Spain

Site Status

Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Servicio de Neurologia, Hospital Universitario i Politécnic La Fe

Valencia, , Spain

Site Status

Department of Neurology, Salford Royal NHS Foundation Trust

Salford, Manchester, United Kingdom

Site Status

Countries

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United States Belgium Canada France Netherlands Spain United Kingdom

Other Identifiers

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2015-002379-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLN-PXT3003-03

Identifier Type: -

Identifier Source: org_study_id

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