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

Charcot-Marie-Tooth Disease, Type IA Clinical Trial

— PLEO-CMT-FU  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03023540
• Other study ID #: CLN-PXT3003-03
• Secondary ID: 2015-002379-81
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 7, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Pharnext S.C.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 187
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years to 67 Years

Eligibility

Inclusion Criteria after September 18th 2017:

• 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

Inclusion Criteria until September 18th 2017:

• 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)

Related Conditions & MeSH terms

• Charcot-Marie-Tooth Disease
• Charcot-Marie-Tooth Disease, Type IA
• Hereditary Sensory and Motor Neuropathy
• Nerve Compression Syndromes
• Tooth Diseases

Intervention

Drug:
• PXT3003
Liquid oral solution, twice 5 mL (Dose 1) bid

Locations

Country	Name	City	State
Belgium	Departement of Neurology, UZ Leuven	Leuven
Canada	University Hospital of Quebec	Quebec
France	Cntre de Reference des Maladies Neuromusculaires, Hopital Swynghedauwl, CHU Lille	Lille
France	Centre de Reference des Neuropathies Peripheriques Rare, Hopital Dupuytren, CHU Limoges	Limoges
France	Service de Neurologie et du Sommeil, CHU Lyon Sud	Lyon
France	Centre de Reference des Maladie Neuromusculaires, CHU la Timone	Marseille
France	Centre de Reference des Maladie Neuromusculaires, Hotel Dieu, CHU de Nantes	Nantes
France	Service de Neurologie, Hopital Kremlin Bicetre	Paris
Netherlands	Departement of Neurology, Academic Medical Center	Amsterdam
Spain	Department of neurology, Hospital Univesitario de Bellvitge	Barcelona
Spain	Servicio de Neurologia, Hospital Universitario La Paz	Madrid
Spain	Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio	Sevilla
Spain	Servicio de Neurologia, Hospital Universitario i Politécnic La Fe	Valencia
United Kingdom	Department of Neurology, Salford Royal NHS Foundation Trust	Salford	Manchester
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Department of Neurology, McKnight Brain Institute	Gainesville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Department of Neurology, Cedars-Sinai Medical Center	Los Angeles	California
United States	Department of Neurology, University of Minnesota	Minneapolis	Minnesota
United States	Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center	New York	New York
United States	Department of Neurology and Psichiatry, Saint Louis University	Saint Louis	Missouri
United States	Saint Luke's Rehabilitation Institute	Spokane	Washington

Sponsors (7)

Lead Sponsor	Collaborator
Pharnext S.C.A.	Amarex, Eurofins Optimed, Greenphire, Premier Research Group plc, Synteract HCR (Syneos Health), Theradis

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Through plasma concentration of PXT3003	Measurement of baclofen, naltrexone and 6-beta-naltrexone plasma concentration at the through	at month 6 and 9
Other	Peak plasma concentration of PXT3003	Measurement of baclofen, naltrexone and 6-beta-naltrexone plasma concentration at the through	at month 6 and 9
Primary	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	Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome	Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome	9 or 24 months
Secondary	Incidence of adverse events leading to withdrawal of study drug	Incidence of adverse events leading to withdrawal of study drug	9 or 24 months
Secondary	Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items	Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items	9 or 24 months
Secondary	Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items	Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items	9 or 24 months
Secondary	Nine-hole Peg Test (9-HPT)	Nine-hole Peg Test (9-HPT)	9 or 24 months
Secondary	Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides)	Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides)	9 or 24 months
Secondary	Time to walk 10 meters	Time to walk 10 meters	9 or 24 months
Secondary	Compound Muscle Action Potential (CMAP) on ulnar nerve	Compound Muscle Action Potential (CMAP) on ulnar nerve	9 or 24 months
Secondary	Sensory Nerve Action Potential (SNAP) on radial nerve	Sensory Nerve Action Potential (SNAP) on radial nerve	9 or 24 months
Secondary	Nerve conduction velocity (NCV)	Nerve conduction velocity (NCV)	9 or 24 months
Secondary	Quality of Life (EQ-5D)	Quality of Life (EQ-5D)	9 or 24 months
Secondary	Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient)	Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient)	9 or 24 months