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

NCT03023540 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CLN-PXT3003-032015-002379-81
• Study Type: interventional
• Target: 187
• Locations: 7 countries
• Sites: 23

Brief Summary

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).

Conditions

Charcot-Marie-Tooth Disease, Type IA

Keywords

Charcot Marie Tooth Type 1A; Peripheral neuropathy; PXT3003

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A

  Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A

  9 or 24 months

Secondary Outcomes (12)

• Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome

  9 or 24 months

• Incidence of adverse events leading to withdrawal of study drug

  9 or 24 months

• Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items

  9 or 24 months

• Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items

  9 or 24 months

• Nine-hole Peg Test (9-HPT)

  9 or 24 months

Other Outcomes (2)

• Through plasma concentration of PXT3003

  at month 6 and 9

• Peak plasma concentration of PXT3003

  at month 6 and 9

Study Arms (2)

PXT3003 dose 1

ACTIVE COMPARATOR

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

Drug: PXT3003

PXT3003 dose 2

ACTIVE COMPARATOR

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)

Drug: PXT3003

Interventions

PXT3003 DRUG

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

PXT3003 dose 1; PXT3003 dose 2

Eligibility Criteria

• Age: 17 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Pharnext S.C.A.: lead
• Synteract HCR (Syneos Health): collaborator
• Premier Research: collaborator
• Greenphire: collaborator
• Theradis: collaborator
• Amarex: collaborator
• Eurofins Optimed: collaborator

Study Sites (23)

Department of Neurology, Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Department of Neurology, McKnight Brain Institute

Gainesville, Florida, 32610, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109-5322, United States

Location

Department of Neurology, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Department of Neurology and Psichiatry, Saint Louis University

St Louis, Missouri, 63104-1027, United States

Location

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

New York, New York, 10032, United States

Location

Saint Luke's Rehabilitation Institute

Spokane, Washington, 99202-1330, United States

Location

Departement of Neurology, UZ Leuven

Leuven, Belgium

Location

University Hospital of Quebec

Québec, Quebec, G1J 1Z4, Canada

Location

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

Lille, France

Location

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

Limoges, France

Location

Service de Neurologie et du Sommeil, CHU Lyon Sud

Lyon, France

Location

Centre de Reference des Maladie Neuromusculaires, CHU la Timone

Marseille, France

Location

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

Nantes, France

Location

Service de Neurologie, Hopital Kremlin Bicetre

Paris, France

Location

Departement of Neurology, Academic Medical Center

Amsterdam, Netherlands

Location

Department of neurology, Hospital Univesitario de Bellvitge

Barcelona, Spain

Location

Servicio de Neurologia, Hospital Universitario La Paz

Madrid, Spain

Location

Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Servicio de Neurologia, Hospital Universitario i Politécnic La Fe

Valencia, Spain

Location

Department of Neurology, Salford Royal NHS Foundation Trust

Salford, Manchester, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Peripheral Nervous System Diseases

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Shahram Attarian, MD

  CHU la Timone, Marseille, France

  PRINCIPAL INVESTIGATOR

• Teresa Sevilla, MD

  Hospital Universitario i Politécnico La F, Valencia, Spain

  PRINCIPAL INVESTIGATOR

• Marianne de Visser, MD

  Academic Medical Center, Amsterdam, Netherlands

  PRINCIPAL INVESTIGATOR

• Mark Roberts, MD

  Selor Royal NHS Foundation Trust, Manchester, UK

  PRINCIPAL INVESTIGATOR

• Florian Thomas, MD PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 26, 2016
• First Posted: January 18, 2017
• Study Start: March 7, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); FR (6); NL (1); GB (1); ES (4); US (9); BE (1)