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Assessing Long Term Safety and Tolerability of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A (PLEO-CMT-FU)

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ClinicalTrials.gov Identifier: NCT03023540
Recruitment Status : Recruiting
First Posted : January 18, 2017
Last Update Posted : May 7, 2018
Sponsor:
Collaborators:
SynteractHCR
Syneos Health
Information provided by (Responsible Party):
Pharnext SA

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, will be eligible to continue in the extension study CLN-PXT3003-03.

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

Patients previously randomised to PXT3003 dose 1 (5 mL) in the extension study (CLN-PXT3003-03) before September 18th 2017 will continue on dose 1 (5 mL). Patients previously randomised to PXT3003 dose 2 (5 mL) in the extension study (CLN-PXT3003-03) before September 18th 2017 will continue on PXT3003 twice dose 1 (2x5 mL).


Condition or disease Intervention/treatment Phase
Charcot-Marie-Tooth Disease, Type IA Drug: PXT3003 Phase 3

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 will have completed the 15-month treatment with PXT3003. September 18th 2017, the PXT3003 dose 2 was prematurely discontinued by the Sponsor. Thereafter, patients will be allowed for entry in this extension study (CLN-PXT3003-03) for a 9-month treatment with PXT3003. Thus patients initially randomised to active treatment will have used PXT3003 for up to 24 months, whereas patients initially randomized to inactive treatment will have used PXT3003 for up to 9 months.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 323 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: International, Multi-center, Open Label, 9-month Follow-up Extension Study Assessing the Long-term Safety and Tolerability of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A
Actual Study Start Date : March 7, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Active Comparator: PXT3003 dose 1
PXT3003: Liquid oral solution, 5 mL bid (taken morning and evening with food) for 9 consecutive months
Drug: PXT3003
Liquid oral solution, 5 mL bid for 9 consecutive months

Active Comparator: PXT3003 dose 2
PXT3003: Liquid oral solution, 5 mL bid (taken morning and evening with food) for 9 consecutive months
Drug: PXT3003
Liquid oral solution, 5 mL bid for 9 consecutive months




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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 [ Time Frame: 9 or 24 months ]
  3. 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 [ Time Frame: 9 or 24 months ]
  5. 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) [ Time Frame: 9 or 24 months ]
  7. Time to walk 10 meters [ Time Frame: 9 or 24 months ]
  8. Compound Muscle Action Potential (CMAP) on ulnar nerve [ Time Frame: 9 or 24 months ]
  9. Sensory Nerve Action Potential (SNAP) on radial nerve [ Time Frame: 9 or 24 months ]
  10. Nerve conduction velocity (NCV) [ Time Frame: 9 or 24 months ]
  11. Quality of Life [ Time Frame: 9 or 24 months ]
    EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D

  12. 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 Outcome Measures:
  1. Through plasma concentration of PXT3003 [ Time Frame: at month 6 and 9 ]
    Measurement of baclofen, naltrexone and 6-beta-naltrexone plasma concentration at the through

  2. Peak plasma concentration of PXT3003 [ Time Frame: at month 6 and 9 ]
    Measurement of baclofen, naltrexone and 6-beta-naltrexone plasma concentration at the through



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Ages Eligible for Study:   16 Years to 67 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03023540


Contacts
Contact: Rene Goedkoop, MD +33 1 41 09 22 30 rgoedkoop@pharnext.com
Contact: Daniel Cohen, MD PhD +33 1 41 09 22 30 dcohen@pharnext.com

  Show 27 Study Locations
Sponsors and Collaborators
Pharnext SA
SynteractHCR
Syneos Health
Investigators
Principal Investigator: Shahram Attarian, MD CHU la Timone, Marseille, France
Principal Investigator: Peter Young, MD University Hospital Munster, Germany
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

Responsible Party: Pharnext SA
ClinicalTrials.gov Identifier: NCT03023540     History of Changes
Other Study ID Numbers: CLN-PXT3003-03
2015-002379-81 ( EudraCT Number )
First Posted: January 18, 2017    Key Record Dates
Last Update Posted: May 7, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pharnext SA:
Charcot Marie Tooth Type 1A
Peripheral neuropathy
PXT3003

Additional relevant MeSH terms:
Tooth Diseases
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Stomatognathic Diseases
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn