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Active, not recruitingNCT03023540PLEO-CMT-FUUpdated Feb 20, 2024

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

A Phase 3 interventional study of PXT3003 in Charcot-Marie-Tooth Disease, Type IA, sponsored by Pharnext S.C.A.. Active, not recruiting at 23 sites in 7 countries. Open to participants aged 17 Years to 67 Years. Per ClinicalTrials.gov, last updated 2024-02-20.

Sponsored by Pharnext S.C.A. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
187
Allocation
Non-randomized
Ages
17 Years to 67 Years
Sex
All
01

Study 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).

Read the detailed 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).

02

Conditions studied

  • Charcot-Marie-Tooth Disease, Type IA

Keywords

  • Charcot Marie Tooth Type 1A
  • Peripheral neuropathy
  • PXT3003
03

Who can participate

Ages eligible
17 Years to 67 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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)
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
187 participants (actual)

Study arms

  • Active comparator
    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

    Drug: PXT3003

  • Active comparator
    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)

    Drug: PXT3003

Interventions

  • DrugPXT3003

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

05

What researchers measure

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

    Time frame: 9 or 24 months

Secondary outcomes

  1. 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

    Time frame: 9 or 24 months

  2. Incidence of adverse events leading to withdrawal of study drug

    Incidence of adverse events leading to withdrawal of study drug

    Time frame: 9 or 24 months

  3. 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

    Time frame: 9 or 24 months

  4. 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

    Time frame: 9 or 24 months

  5. Nine-hole Peg Test (9-HPT)

    Nine-hole Peg Test (9-HPT)

    Time frame: 9 or 24 months

  6. 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)

    Time frame: 9 or 24 months

  7. Time to walk 10 meters

    Time to walk 10 meters

    Time frame: 9 or 24 months

  8. Compound Muscle Action Potential (CMAP) on ulnar nerve

    Compound Muscle Action Potential (CMAP) on ulnar nerve

    Time frame: 9 or 24 months

  9. Sensory Nerve Action Potential (SNAP) on radial nerve

    Sensory Nerve Action Potential (SNAP) on radial nerve

    Time frame: 9 or 24 months

  10. Nerve conduction velocity (NCV)

    Nerve conduction velocity (NCV)

    Time frame: 9 or 24 months

  11. Quality of Life (EQ-5D)

    Quality of Life (EQ-5D)

    Time frame: 9 or 24 months

  12. 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)

    Time frame: 9 or 24 months

Other outcomes

  1. Through plasma concentration of PXT3003

    Measurement of baclofen, naltrexone and 6-beta-naltrexone plasma concentration at the through

    Time frame: at month 6 and 9

  2. Peak plasma concentration of PXT3003

    Measurement of baclofen, naltrexone and 6-beta-naltrexone plasma concentration at the through

    Time frame: at month 6 and 9

06

Study locations

23 sites
  • Department of Neurology, Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • Department of Neurology, McKnight Brain Institute
    Gainesville, Florida 32610, United States
  • University of Kansas Medical Center
    Kansas City, Kansas 66160, United States
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
  • University of Michigan Health System
    Ann Arbor, Michigan 48109-5322, United States
  • Department of Neurology, University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Department of Neurology and Psichiatry, Saint Louis University
    Saint Louis, Missouri 63104-1027, United States
  • Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center
    New York, New York 10032, United States
  • Saint Luke's Rehabilitation Institute
    Spokane, Washington 99202-1330, United States
  • Departement of Neurology, UZ Leuven
    Leuven, Belgium
  • University Hospital of Quebec
    Quebec, G1J 1Z4, Canada
  • 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, France
  • Departement of Neurology, Academic Medical Center
    Amsterdam, Netherlands
  • 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, Spain
  • Department of Neurology, Salford Royal NHS Foundation Trust
    Salford, Manchester M6 8HD, United Kingdom
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03023540
Lead sponsor
Pharnext S.C.A.
Collaborators
Synteract HCR (Syneos Health), Premier Research Group plc, Greenphire, Theradis, Amarex, Eurofins Optimed
Responsible party
Sponsor
First posted
Jan 18, 2017
Start date
Mar 7, 2017
Primary completion
Dec 31, 2024 (estimated)
Completion
Dec 31, 2024 (estimated)
Last update
Feb 20, 2024

Study contacts

Shahram Attarian, MD
principal investigator · CHU la Timone, Marseille, France
Teresa Sevilla, MD
principal investigator · Hospital Universitario i Politécnico La F, Valencia, Spain
Marianne de Visser, MD
principal investigator · Academic Medical Center, Amsterdam, Netherlands
Mark Roberts, MD
principal investigator · Selor Royal NHS Foundation Trust, Manchester, UK
Florian Thomas, MD PhD
principal investigator · Seton Hall-Hackensack-Meridian School of Medicine, Hackensack, USA

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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