Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PREMIER)
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|ClinicalTrials.gov Identifier: NCT04762758|
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : July 21, 2021
|Condition or disease||Intervention/treatment||Phase|
|Charcot-Marie-Tooth Disease||Drug: (RS)-baclofen, naltrexone hydrochloride and D-sorbitol Drug: Placebo||Phase 3|
This international, multi-center, randomized, double-blind, placebo-controlled, Phase III clinical study is designed to evaluate PXT3003 versus placebo in male and non-pregnant female subjects with genetically confirmed CMT1A of mild-to-moderate severity (CMTNS-V2 score >2 and ≤18) aged 16 to 65 years.
The study will be conducted in approximately 48 sites worldwide. Genetically confirmed CMT1A subjects will be screened (approximately 500 subjects assuming a 30% screen failure rate) and randomized in a 1:1 ratio to receive either oral PXT3003 daily or matching placebo for 15 months. A total of approximately 350 subjects will be enrolled. Visits will take place at Screening (up to -35 days), Baseline (Day 1), and Months 3, 6, 9, 12, and 15. Randomization will occur at the Baseline (Day 1) Visit. Telephone contacts (TC) will take place at Weeks 2 or 3, Month 1 and 2, and then monthly between subsequent in-person visits. A Safety follow-up visit will be conducted at Month 16.
Subjects will receive in-clinic dosing of study medication at visits on Day 1 and Months 6, 12, and 15. Study medication will be dispensed for outpatient dosing on Day 1 and Months 3, 6, 9, and 12. During outpatient dosing, subjects will complete the Study Medication Diary using an application on their tablet, phone, or computer. The Study Medication Diary will be evaluated, along with returned unused study medication, as part of study drug compliance at visits at Months 3, 6, 9, 12, and 15.
The primary outcome measure (mONLS) and the 10-Meter Walk Test (10mWT), along with the Columbia Suicide Severity Rating Scale (C-SSRS) will be evaluated at each post-Screening visit. The other secondary outcome measures, exploratory outcome, and safety/tolerability assessments will be evaluated as per Schedule of Activities (SOA). A Safety Follow-Up Visit will take place 30 days (Month 16) after the active treatment period ends (Month 15). A Data Safety and Monitoring Board (DSMB) will meet on a scheduled basis throughout the study to review safety data and will reconvene on an ad hoc basis as necessary.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||350 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||PXT3003 and its matching placebo will have the same presentation, the same aspect and taste in order to be indistinguishable, and they will be supplied and used in the same conditions.|
|Official Title:||A Multi-center, Randomized, Double-blind, Placebo Controlled Phase III Study to Assess the Efficacy, Safety, and Tolerability of PXT3003 in Charcot-Marie-Tooth Type 1A (CMT1A)|
|Actual Study Start Date :||March 30, 2021|
|Estimated Primary Completion Date :||October 31, 2023|
|Estimated Study Completion Date :||March 31, 2024|
Liquid oral solution, 10 mL twice a day, morning and evening with food
Drug: (RS)-baclofen, naltrexone hydrochloride and D-sorbitol
oral fixed dose combination
Other Name: PXT3003
Placebo Comparator: Placebo
Liquid oral solution, 10 mL twice a day, morning and evening with food
liquid oral solution
- modified Overall Neuropathy Limitation Scale (mONLS) [ Time Frame: From Baseline to Month 15 ]The modified ONLS is a disability scale that was derived and improved from the Overall Disability Sum Score to measure limitations in the everyday activities of the upper limbs (rated on 5 points) and the lower limbs (rated on 7 points).38 The total score goes from 0 (no disability) to 12 (maximum disability). Lower values in the ONLS indicate a better clinical condition.
- 10-Meter Walk Test [ Time Frame: From Baseline to Month 15 ]The 10mWT is simple to administer, standardized, and valid performance evaluation of functional mobility and gait that has been proven reliable in neurologic disorders, including CMT. Results recorded are the time to walk 10 meters and the number of steps performed.
- Quantified Muscular Testing (QMT) (bilateral foot dorsiflexion dynamometry) [ Time Frame: From Baseline to Month 15 ]QMT is used to evaluate motor strength in CMT1A.The following muscles will be evaluated: tibialis anterior (right and left). The best value on three consecutive and reproducible tests will be collected in the electronic Case Record Form (eCRF) for each muscle.
- Patient Global Impression of Severity (PGI-S) [ Time Frame: From Baseline to Month 15 ]The PGI-S is a validated tool that is used to rate the severity of a specific condition. Subjects will rate their health status over the past week. The PGI-S is a 1-item questionnaire on a 5-point scale and subjects will be asked to rate the severity of their condition from "None" (Score = 1) to "Very Severe" (Score = 5). Assessments obtained over the course of the study will be compared to baseline, prior to initiation of treatment.
- Patient Global Impression of Change (PGI-C) [ Time Frame: From Baseline to Month 15 ]The PGI-C scale is a validated generic tool for assessment of overall change in the severity of illness following treatment. Subjects will rate how they feel now compared with how they felt before receiving study drug on a 7-point scale where 1 is "Very much improved" and 7 is "Very much worse".
- CMTNS-V2 [ Time Frame: From Baseline to Month 15 ]
CMTNS is a specific scale designed to assess severity of impairment in CMT disease. Although not completely validated, it provides a single and reliable measure of CMT severity. It is a 36-point scale based on 9 items: 5 of them quantify impairment (sensory symptoms, pin sensibility, vibration, arm, and leg strength), 2 activity limitations (motor symptoms arms and legs) and 2 electrophysiological data (amplitudes of ulnar compound muscle action potential and sensory nerve action potential). Increased scores indicate a worsening of the function: the scores categorize a disability as mild (0 to10), moderate (11 to 20) and severe (21 to 36).
A modified version 2 (CMTNS-V2) was issued in 2011 to attempt to reduce floor and ceiling effects and to standardize patient assessment.
- QMT (hand grip) [ Time Frame: From Baseline to Month 15 ]QMT is used to evaluate motor strength in CMT1A. The following muscles will be evaluated: hand grip (right and left). The best value on three consecutive and reproducible tests will be collected in the eCRF for each muscle.
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): NCT04762758
|Contact: Michele Fradkin||+33 1 41 09 22 firstname.lastname@example.org|
|Contact: Adrian Hepner, MD||+33 1 41 09 22 email@example.com|
|Principal Investigator:||Sharam Attarian, MD||CHU la Timone, Marseille , France|
|Principal Investigator:||Mario Saporta, MD||University of Miami Miller School of Medicine, USA|