Phase 3 trial of PXT3003 in Charcot-Marie-Tooth (CMT) Type 1A patients
- Conditions
- Charcot Marie Tooth Type 1AMedDRA version: 20.0Level: LLTClassification code 10008414Term: Charcot-Marie-Tooth diseaseSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2020-004805-30-DE
- Lead Sponsor
- Pharnext SCA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 387
1) 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 In the event of a negative genetic test result, the subject will be withdrawn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.
2) Able to provide written informed consent/assent and comply with study procedures
3) Mild-to-moderate severity assessed by CMTNS-v2 score >2 and =18
4) Muscle weakness in at least foot dorsiflexion on clinical assessment
5) Ulnar nerve motor conduction time of at least 15m/s
6) If taking prescribed psychoactive drug(s) (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.
7) If taking prescribed or 'over-the-counter' analgesic medication(s) (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.
8) 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:
o Oral
o Intravaginal
o Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
o Oral
o Injectable
o Implantable
• IUD
• IUS
• 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)
9) 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.
For subjects consenting to enter the OLE Period, the following Inclusion
criteria will be confirmed/reassessed on Screening Day (SV6) of the OLE
Period:
1. Able to provide written informed consent/assent and comply with
study procedures.
2. 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:
o Oral
o Intravaginal
o Transdermal
• Progestogen-only hormonal contraception associated with inhibition
of ovulation:
o Oral
o Injectable
o Implantable
•IUD
•IUS
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence
or (c) of non-childbearing potential (ie, no menses for =12 consecutive
months without any other underlying medical cause).
3. If male, the subject must have had a vasectomy or must use a reliable method of
1.Subjects previously enrolled in any PXT3003 study.
2.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).
3.CMT of any subtype other than 1A.
4.ONLS score of 0.
5.Known clinically significant motor or sensory abnormalities secondary to a different neurological cause. 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.
6.Subjects who have had any surgery or have a concomitant disorder 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 carpal tunnel syndrome will not be excluded from participating in this study.
7.Known peripheral neuropathy, myopathy, or neuromuscular disorder of any other kind. 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.
8.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.
9.Known hypersensitivity or intolerance to PXT3003 (or matching placebo), including any of its active ingredients, and/or any of its excipients.
10.Concomitant treatments including but not limited to baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, potent central nervous system depressants, 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.
11.History of porphyria.
12.Diagnosis or history of substance use disorder by DSM-V criteria within the past 12 months.
13.Medical or recreational use of marijuana in the 3 months prior to the Screening Visit.
14.Active suicidality
15.Currently active major depression, as determined by a BDI-II score =20.
16.Currently lactating, pregnant, or planning on becoming pregnant during the study.
17.ALT or AST levels greater than 2 times the ULN.
18.Significant renal impairment as determined by GFR of less than 50 mL/min.
19.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.
20.Subject is a dependent and/or relative of the Sponsor or Principal Investigator.
For subjects consenting to enter the OLE Period, the following criteria
will be confirmed/reassessed on SV6 of the OLE Period
1.Any clinically significant and/or uncontrolled medical condition that, in the opinion of the investigator, could be a confound factor, may increase subject's risk, or may preclude successful participation or completion of the study.
2.Concomitant treatments including but not limited to baclofen,
naltrexone, sorbitol (pharmaceutical form) other than PXT3
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of treatment with PXT3003 (a fixed-dose combination of (RS)-baclofen, naltrexone hydrochloride, and D-sorbitol) compared to placebo in subjects with CMT1A;Secondary Objective: To evaluate the safety and tolerability of PXT3003 treatment in subjects with CMT1A;Primary end point(s): The change in the modified Overall Neuropathy Limitation Scale (mONLS) between baseline and the Month 15 visit. ;Timepoint(s) of evaluation of this end point: Month 15 visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The change from baseline to month 15 in the following outcome measures in hierarchical order:<br>1) 10-Meter Walk Test (10mWT)<br>2) CMTNS-V2<br>3) Patient Global Impression of Severity (PGI-S)<br>4) Patient Global Impression of Change (PGI-C)*<br>5) Quantified Muscular Testing (hand grip)<br>6) Quantified Muscular Testing (bilateral foot dorsiflexion dynamometry)<br>* Because the PGI-C is already a change assessment, the change from Baseline is not needed for this endpoint.<br>;Timepoint(s) of evaluation of this end point: Month 15 visit