Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients

Status unconfirmed · Phase 3 · Has a placebo group

Conditions studied: Charcot-Marie-Tooth Disease

In brief

The study will consist of 2 periods: Double-blind Treatment and Open-Label Extension(OLE) Period. -Double-blind Treatment Period - This will be randomized, double-blind, placebo-controlled part of the study which will be conducted in parallel groups, ie,1 group receiving the active treatment (PXT3003) and the other group receiving placebo. Primary endpoint of the study will be assessed at Month 15. -Open-label Extension (OLE) Period - All subjects completing Double-blind Treatment Period will be given an opportunity to enter the OLE Period of the study and receive the active treatment (PXT3003). The duration of the OLE Period will be based on Sponsor discretion, ie, Sponsor intends to keep the study open until the study drug PXT3003 is commercially available. During this period, the long-term safety and efficacy of PXT3003 will be assessed as an exploratory objective. Double-blind Treatment Period Objectives: Primary: To evaluate the efficacy of treatment with PXT3003 (a fixed-dose combination of \[RS\]-baclofen, naltrexone hydrochloride \[HCl\], and D-sorbitol) compared to placebo in subjects with Charcot-Marie-Tooth disease type 1A (CMT1A). Secondary: To evaluate the safety and tolerability of PXT3003 treatment in subjects with CMT1A. Exploratory: To characterize the relationship between plasma biomarkers and response to PXT3003 treatment. OLE Period Objective: Exploratory: To evaluate the long-term safety and efficacy of PXT3003.

Key facts

Study ID

NCT04762758

Run by

Pharnext S.C.A.

People needed

350

Starts

2021-03-30

Expected to finish

2024-04-19

Last updated by the study team

2024-04-03

Who can join

Age: 16 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male and non-pregnant female subjects, aged 16 to 65 years with a genetically proven diagnosis of CMT1A. Notes: a) A report of a genetic test confirming PMP22 duplication and therefore a diagnosis of CMT1A must be available in the subject's record at the clinical site. b) In the absence of a report of a genetic test confirming PMP22 duplication in the subject's medical record, a confirmatory genetic test must be conducted via the central laboratory as part of Screening. c) In the exceptional case wherein subject was randomized into the study without meeting(a) or (b), an unscheduled confirmatory genetic test will be performed. In the event of a negative genetic test result, the subject will be withdrawn from the study.
• Able to provide written informed consent/assent and comply with study procedures.
• Mild-to-moderate severity assessed by a CMTNS-V2 score >2 and ≤18.
• Muscle weakness in at least foot dorsiflexion on clinical assessment.
• Ulnar nerve motor conduction time of at least 15 m/s.
• If taking prescribed psychoactive drugs(eg, antidepressants, stimulants, tranquilizers, anti-epileptics) for CMT1A, should be on a stable dose for at least 4 weeks prior to randomization, which is not planned to be changed.
• If taking prescribed or 'over-the-counter' analgesic medications (eg, paracetamol/acetaminophen, nonsteroidal anti-inflammatory drugs) for CMT1A, should be on a stable dose for at least 2 weeks prior to randomization, which is not planned to be changed.
• If female, subject must be: (a) surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or (b) of childbearing potential and using a birth control method such as:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral
• Intravaginal
• Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
• Oral
• Injectable
• Implantable
• Intrauterine device
• Intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence or (c) Of non-childbearing potential (i.e., no menses for ≥ 12 consecutive months without any other underlying medical cause)
• If male, the subject must have had a vasectomy or must use a reliable method of birth control with their partner or total abstinence from sexual intercourse. The subject must agree to continue using their selected method of birth control with their sexual partner during the study and for 120 days after study completion.

You may not qualify if…

• Subjects previously enrolled in any PXT3003 study.
• Subjects living in the same household and enrolled in a PXT3003 study (due to potential lack of adequate storage for study material, risk of mixing treatments and potential unblinding).
• CMT of any subtype other than 1A.
• ONLS score of 0.
• Known clinically significant motor or sensory abnormalities secondary to a different neurological cause (eg, diabetes, alcohol, vascular, autoimmune, neoplastic, neurodegenerative, human immunodeficiency virus, etc.). Note: subjects with diagnosis of unilateral carpal tunnel syndrome at least 1 year prior to Screening Visit, that is asymptomatic at the time of Screening Visit, will not be excluded from participating in this study.
• Subjects who have had any surgery or have a concomitant disorder (eg, severe arthrosis) that reduces the mobility of the ankle or wrist making it, in the opinion of the investigator, difficult to assess the efficacy of the treatment. Note: subjects with surgical repair of unilateral carpel tunnel syndrome will not be excluded from participating in this study.
• Known peripheral neuropathy, myopathy, or neuromuscular disorder of any other kind. Note: subjects with diagnosis of unilateral carpal tunnel syndrome at least 1year prior to Screening Visit, that is asymptomatic at the time of Screening Visit, will not be excluded from participating in this study.
• Any other clinically significant and/or uncontrolled medical condition that, in the opinion of the investigator, could be a confound, may increase subject's risk, or may preclude successful participation or completion of the study.
• Known hypersensitivity or intolerance to PXT3003( or matching placebo), including any of its active ingredients( baclofen, naltrexone, or sorbitol), and/or any of its excipients( acetate buffer, sodium methyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, or isoamyl acetate).
• Concomitant treatments including but not limited to baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, potent central nervous system depressants (such as barbiturates, long-acting benzodiazepines, and neuroleptics), and potentially neurotoxic drugs such as amiodarone, chloroquine, and chemotherapeutics capable of inducing peripheral neuropathy. Subjects able to stop these medications at least 2 weeks before randomization and for the study duration may be included. Subjects with positive urine drug screen at Baseline Visit will be excluded, except for permitted use of codeine and benzodiazepines.
• History of porphyria.
• Diagnosis or history of substance use disorder by Diagnostic and Statistical Manual of Mental Disorders-5th Edition criteria within the past 12 months.
• Medical or recreational use of marijuana in the 3 months prior to the Screening Visit.
• Active suicidality (eg, any suicide attempts within the past 12 months or any current suicidal intent, including a plan, as assessed by the C SSRS score of "YES" on questions 4 or 5; and/or based on clinical evaluation by the investigator).
• Currently active major depression, as determined by a Beck Depression Inventory-II (BDI-II) score ≥20.
• Currently lactating, pregnant, or planning on becoming pregnant during the study.
• Alanine aminotransferase or aspartate aminotransferase levels greater than 2 times the upper limit of normal.
• Significant renal impairment as determined by glomerular filtration rate of less than 50 mL/min.
• Subject has participated in an investigational drug or device study within 30 days prior to the Screening Visit or plans to participate in an investigational drug or device study during the course of this study.
• Subject is a dependent and/or relative of the Sponsor or Principal Investigator.
• OLE Period
• Inclusion Criteria:
• Able to provide written informed consent/assent and comply with study procedures.
• If female, subject must be (a) surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or (b) of childbearing potential and using a birth control method such as:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

Where it is running

• Cedars-Sinai Medical Center — Los Angeles, California, United States
• UCLA Department of Psychiatry and Biobehavioral Sciences — Los Angeles, California, United States
• UC Davis Health Department of Physical Medicine and Rehabilitation — Sacramento, California, United States
• Hospital for Special Care — New Britain, Connecticut, United States
• University of Florida Clinical Research Center — Gainesville, Florida, United States
• University of Miami Leonard M. Miller School of Medicine — Miami, Florida, United States
• Advent Health Medical Group Neurology Orlando — Orlando, Florida, United States
• University of Kansas Medical Center Research Institute — Fairway, Kansas, United States
• Massachusetts General Hospital Neuromuscular Diagnostic Center — Boston, Massachusetts, United States
• University of Minnesota Health — Minneapolis, Minnesota, United States
• MU Health Care Neurology and Sleep Disorders Clinic — Columbia, Missouri, United States
• Hackensack Meridian Health Hackensack University Medical Center — Hackensack, New Jersey, United States
• Colombia University Department of Neurology — New York, New York, United States
• UNC Department of Neurology Peripheral Neuropathy Center — Chapel Hill, North Carolina, United States
• Atrium Health Neurosciences Institute — Charlotte, North Carolina, United States
• The Ohio State University Wexner Medical Center — Columbus, Ohio, United States
• Oregon Neurology — Springfield, Oregon, United States
• National Neuromuscular Research Institute — Austin, Texas, United States
• Neurology Clinic at University of Washington Medical Center — Seattle, Washington, United States
• Providence St. Luke's Rehabilitation Medical Center — Spokane, Washington, United States
• Universitaire Ziekenhuizen Leuven — Leuven, Belgium
• Ottawa Hospital Research Institute- Neuromuscular Research Centre — Ottawa, Ontario, Canada
• UHN Toronto General Hospital Krembil Neuroscience Centre — Toronto, Ontario, Canada
• CIUSS de Saguenay-Lac-Saint-Jean Centre d'etudes Cliniques — Chicoutimi, Quebec, Canada
• Montreal Neurological Institute and Hospital-Clinical Research Unit — Montreal, Quebec, Canada

Full record on ClinicalTrials.gov

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