Clinical trial NCT05092841: A Study to Assess the Efficacy and Safety of PXT3003 in Charcot-Marie-Tooth Type 1A
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Charcot-Marie-Tooth Type 1A
Lead sponsor: Tasly Pharmaceutical Group Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-10-26
Enrollment: 176
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 16 to 65 years (included boundary value), of either sex;
2. 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:

1. Being allergic to RS-baclofen, naltrexone HCL, D-sorbitol or any component in pxt3003 excipients or having other serious prior allergic reaction;
2. Existence contraindications of baclofen, naltrexone or sorbitol, such as porphyria;
3. Any other associated cause of peripheral neuropathy such as diabetes mellitus (including diabetes history and glycosylated hemoglobin \>6.5%)
4. Subjects with other neurological diseases affecting the evaluation of study treatment;
5. Patients with the score of ONLS score is 0;
6. 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;
7. Limb surgery had implemented within the first six months of randomization or will be planned before the completion of the clinical trial;
8. Hepatic or renal dysfunction:

   1. TBIL\>1.5×ULN,ALT\>3×ULN,AST\>3×ULN;
   2. Cr\>1.5×ULN;
9. Syphilis antibody and HIV antibody positive subjects;
10. Subjects with tumors indicated by chest radiograph or B-ultrasound;
11. Subjects with alcohol dependence in recent 3 months;
12. Females that are of childbearing potential, pregnant, or are breast-feeding;Subjects who are unable to use appropriate contraceptives during the trial;
13. 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);
14. Subjects unable to complete the follow-up of study;
15. Participated in another clinical trial and used the test drug within the last 30 days;
16. 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;
17. 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.

Primary outcomes:
measure: Overall Neuropathy Limitation Scale (ONLS) score
timeFrame: 15 months
Secondary outcomes:
measure: Treatment responders rate of PXT3003;
timeFrame: 15 months
measure: The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS)
timeFrame: 15 months
measure: Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2);
timeFrame: 15 months
measure: 10-Meter Walk Test (10MWT);
timeFrame: 15 months
measure: Nine-hole peg test (9HPT) for non-dominant hand ;
timeFrame: 15 months
measure: Quantified Muscular Testing (QMT) (grip strength and bilateral foot dorsiflexion dynamometry) ;
timeFrame: 15 months
measure: Electrophysiological parameters Sensory responses measured at ulnar and radial nerves on the non-dominant side:
timeFrame: 15 months
measure: Electrophysiological parameters motor responses measured at ulnar and radial nerves on the non-dominant side
timeFrame: 15 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
city: Guangzhou
country: China
facility: The First Affiliated Hospital，Sun Yat-sen University
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Hohhot
country: China
facility: Inner Mongolia People's Hospital
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Qingdao
country: China
facility: Qilu Hospital of Shandong University（Qingdao）
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine Ruijin Hospital
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University（Hubei General Hospital）
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Tasly Group,Co.Ltd.
name: Rui Liu
role: STUDY_DIRECTOR
References: