A Study to Assess the Efficacy and Safety of PXT3003 in Charcot-Marie-Tooth Type 1A

Sponsor

Tasly GeneNet Pharmaceuticals Co., Ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05092841

Collaborator

(none)

176

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled and multicenter 3 phase trial evaluating the therapeutic effect and safety of CMT1A by PXT3003. This double-blind study will assess in parallel groups 1 dose of PXT3003 compared to Placebo in CMT1A patients treated for 15 months.

Condition or Disease	Intervention/Treatment	Phase
Charcot-Marie-Tooth Type 1A	Drug: PXT3003 Drug: PXT3003 placebo	Phase 3

Detailed Description

This multi-center, randomized, double-blind, placebo-controlled, Phase III clinical study is designed to evaluate PXT3003 versus placebo in subjects with genetically confirmed CMT1A of mild-to-moderate severity (CMTNS-V2 score >2 and ≤18) aged 16 to 65 years.

Genetically confirmed CMT1A subjects will be screened and randomized in a 1:1 ratio to receive either oral PXT3003 daily or matching placebo for 15 months. A total of approximately 176 subjects will be enrolled.

Visits will take place at Screening (up to -30 days), Baseline , and Months 3, 6, 9, 12, and 15.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

176 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Efficacy and Safety of PXT3003 in Charcot-Marie-Tooth Type 1A (CMT1A) Treated 15 Months

Actual Study Start Date :

Sep 28, 2021

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PXT3003 Liquid oral solution, 10 mL twice a day, morning and evening with food	Drug: PXT3003 Patients will be administered PXT3003 twice daily (bid) at 10mL. Other Names: (RS)-baclofen, naltrexone hydrochloride and D-sorbitol oral fixed dose combination
Placebo Comparator: PXT3003 Placebo Liquid oral solution, 10 mL twice a day, morning and evening with food	Drug: PXT3003 placebo Patients will be administered PXT3003 placebo twice daily (bid) at 10mL. Other Names: liquid oral solution

Arm

Intervention/Treatment

Experimental: PXT3003

Liquid oral solution, 10 mL twice a day, morning and evening with food

Drug: PXT3003

Patients will be administered PXT3003 twice daily (bid) at 10mL.

Other Names:

(RS)-baclofen, naltrexone hydrochloride and D-sorbitol oral fixed dose combination

Placebo Comparator: PXT3003 Placebo

Liquid oral solution, 10 mL twice a day, morning and evening with food

Drug: PXT3003 placebo

Patients will be administered PXT3003 placebo twice daily (bid) at 10mL.

Other Names:

liquid oral solution

Outcome Measures

Primary Outcome Measures

Overall Neuropathy Limitation Scale (ONLS) score [15 months]
The primary efficacy endpoint will be the main effect of the studied treatment on the improvement of disability measured by the Overall Neuropathy Limitation Scale (ONLS) score, summarized at 15 months defined by: the change of the ONLS from baseline to the 15 months.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 in 5 points) and the lower limbs (rated on 7 points) . The total score goes from 0 ( no disability) to 12 (maximum disability).

Secondary Outcome Measures

Treatment responders rate of PXT3003; [15 months]
Responders Rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment.
The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS) [15 months]
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 in 5 points) and the lower limbs (rated on 7 points) . The total score goes from 0 ( no disability) to 12 (maximum disability).
Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2); [15 months]
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).
10-Meter Walk Test (10MWT); [15 months]
Record the time for walk 10 meters . 10m WT is simple to administer, standardized, reliable and valid evaluation of functional exercise capacity and gait that has been proven reliable in neurologic disorders and in CMT patients. Results recorded are the time to walk 10 meters and the number of steps performed.
Nine-hole peg test (9HPT) for non-dominant hand ; [15 months]
The 9-HPT is a simple timed test of fine motor coordination of extremities in the upper limbs.
Quantified Muscular Testing (QMT) (grip strength and bilateral foot dorsiflexion dynamometry) ; [15 months]
QMT is used to evaluate motor strength in CMT1A. The following muscles will be evaluated: hand grip (right and left).
Electrophysiological parameters Sensory responses measured at ulnar and radial nerves on the non-dominant side: [15 months]
The assessment parameters including: Distal motor latency (DML) .
Electrophysiological parameters motor responses measured at ulnar and radial nerves on the non-dominant side [15 months]
The assessment parameters including: Nerve conduction velocity (NCV) .

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged 16 to 65 years (included boundary value), of either sex;
Patients with CMT1A (PMP22 duplication on chromosome 17p11.2) confirmed by gene diagnosis; 3.2 < CMTNS-v2 score ≤ 18;

4.Patients are dorsalis pedis flexor weakness at least (clinical evaluation); 5.Ulnar nerve motor nerve conductance velocity > 15 m/s; 6.Subjects participate in clinical trials and sign informed consent voluntarily , and they have the ability to understand as will as abide by research procedures.

Exclusion Criteria:

Being allergic to RS-baclofen, naltrexone HCL, D-sorbitol or any component in pxt3003 excipients or having other serious prior allergic reaction;
Existence contraindications of baclofen, naltrexone or sorbitol, such as porphyria;
Any other associated cause of peripheral neuropathy such as diabetes mellitus (including diabetes history and glycosylated hemoglobin >6.5%)
Subjects with other neurological diseases affecting the evaluation of study treatment;
Patients with the score of ONLS score is 0;
A history of unstable medical diseases with clinically significant unstable medical diseases (unstable angina pectoris, tumor, blood disease, hepatitis or liver failure, renal failure, etc.) that may cause harm to the subjects participating in this study in the past 1 year;
Limb surgery had implemented within the first six months of randomization or will be planned before the completion of the clinical trial;
Hepatic or renal dysfunction:
TBIL>1.5×ULN,ALT>3×ULN,AST>3×ULN;
Cr>1.5×ULN;
Syphilis antibody and HIV antibody positive subjects;
Subjects with tumors indicated by chest radiograph or B-ultrasound;
Subjects with alcohol dependence in recent 3 months;
Females that are of childbearing potential, pregnant, or are breast-feeding;Subjects who are unable to use appropriate contraceptives during the trial;
Subjects with concomitant treatment 4 weeks before enrollment, including but not limited to baclofen, naltrexone, sorbitol, opioids, vitamin C, levothyroxine and potentially neurotoxic drugs (such as amiodarone and chloroquine);
Subjects unable to complete the follow-up of study;
Participated in another clinical trial and used the test drug within the last 30 days;
Different subjects from the same family and living in the same residence can only include one subject, so as to avoid treatment confusion, affect blind treatment and affect the interpretation of the research results;
Investigators affirm the compliance in a certain subject is poor or there are some other factors that are not suitable to participate in this clinical trial.

Contacts and Locations

Locations

	Site	City	Country
1	Peking University Third Hospital	Beijing	China
2	Xuanwu Hospital Capital Medical University	Beijing	China
3	The First Bethune Hospital of Jilin University	Changchun	China
4	The Third Xiangya Hospital of Central South University	Changsha	China
5	The First Affiliated Hospital of Fujian Medical University	Fuzhou	China
6	Nanfang Hospital Southern Medical University	Guangzhou	China
7	The First Affiliated Hospital，Sun Yat-sen University	Guangzhou	China
8	The Affiliated Hospital of Guizhou Medical University	Guiyang	China
9	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	China
10	The First Affiliated Hospital of Harbin Medical University	Harbin	China
11	The First Affiliated Hospital of Anhui Medical University	Hefei	China
12	Inner Mongolia People's Hospital	Hohhot	China
13	Qilu Hospital of Shandong University	Jinan	China
14	The Second Affiliated Hospital of Nanchang University	Nanchang	China
15	The Affiliated Hospital of Nanjing University Medical School	Nanjing	China
16	Zhongda Hospital Southeast University	Nanjing	China
17	Qilu Hospital of Shandong University（Qingdao）	Qingdao	China
18	Shanghai Jiaotong University School of Medicine Ruijin Hospital	Shanghai	China
19	The First Hospital of China Medical University	Shenyang	China
20	The Second Hospital of Hebei Medical University	Shijiazhuang	China
21	The First Affiliated Hospital of Soochow University	Suzhou	China
22	Renmin Hospital of Wuhan University（Hubei General Hospital）	Wuhan	China
23	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	China
24	Henan Provincial People's Hospital	Zhengzhou	China
25	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	China