A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Efficacy of MTR-601, a Novel Oral Treatment in Patients With Cervical Dystonia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Motric Bio
- 入组人数
- 38
- 试验地点
- 34
- 主要终点
- To evaluate the safety and tolerability of MTR-601 by the incidents of treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
Study MTR-601-201 is an 8-week, randomized, placebo-controlled study to examine the safety, tolerability, and efficacy of MTR-601 in participants with cervical dystonia.
详细描述
Study MTR-601-201 is an 8-week, randomized, placebo-controlled study to examine the safety, tolerability, and efficacy of MTR-601 in participants with cervical dystonia.
Participants will be randomized (1:1) to receive either MTR-601 or matching placebo every day for 4 weeks, after which all participants will be followed for an additional 2 weeks through study treatment washout. The Investigator and Participant will be blinded to the assigned arm. Treatment will be administered via capsules and matching placebo capsules. The total sample size will be approximately 80 participants.
The study will be divided into 3 periods: Screening, Treatment and Follow up.
An initial screening assessment (V1) will occur between Day -90 and Day -2, where individuals will undergo informed consent and have their preliminary eligibility reviewed. Individuals who are found to be eligible will be instructed to not receive their next scheduled botulinum toxin treatment prior to entry into the study.
A full Screening visit (V2) will occur between Day -14 and -1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •will be eligible to participate in the study:
- •Willing to adhere to study procedures and provide written informed consent prior to the start of any study procedures.
- •Confirmed clinical diagnosis of cervical dystonia with the following:
- •Treatment with botulinum toxin injections (any type) on a stable dosing regimen for ≥ 2 consecutive doses at V2 or a history of botulinum toxin injections within the last 5 years which were discontinued for reasons other than lack of efficacy.
- •3 months (90 days) since botulinum toxin injection (≥6 months (180 days) for daxibotulinum toxinA) at V3
- •TWSTRS total score ≥ 20 with the following sub scores at V2:
- •Severity ≥ 15
- •Disability ≥ 3
- •Pain score ≥ 1)
- •Willingness to not use botulinum toxin for duration of their study participation
- •Adults 18-80 years of age at the time of consent.
- •Weight ≥40 kg and body mass index (BMI) ≤35 kg/m
- •Agree to practice highly effective birth control starting at screening and continuing for 30 days (females) or 90 days (males) after study treatment ends.
- •For females any of the following (no donation of eggs/ova is allowed):
- •Abstinence from heterosexual intercourse.
- •Postmenopausal: absence of menses ≥ 12 months (without an alternative medical condition) and FSH ≥ 40 mIU/mL at screening.
- •Surgically sterile: bilateral oophorectomy, salpingectomy, tubal ligation, or hysterectomy ≥180 days prior to screening.
- •Contraceptive implant or intrauterine device.
- •For males any of the following:
- •Abstinence from heterosexual intercourse.
- •Male condom with spermicide or male condom with vaginal spermicide (gel, foam, or suppository).
- •Surgically sterile: post vasectomy or bilateral orchiectomy ≥180 days prior to screening.
- •No donation of sperm is allowed
- •Participants who meet ANY of the following criteria will be excluded from participation in the study:
- •History of, or physical examination findings indicating, clinically significant endocrine, neurological, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or muscle abnormalities or diseases that, in the opinion of the Investigator, renders the participant unsuitable for the study.
- •History of any of the following:
- •Cervical dystonia due to trauma
- •Chronic contractures in the head and neck musculature
- •Generalized dystonia of any type
- •Myasthenia gravis (MG) or amyotrophic lateral sclerosis (ALS)
- •Use of the following treatment for cervical dystonia:
- •Botulinum toxin (of any type) within 3 months (90 days) (6 months (180 days) for daxibotulinum toxinA) at Baseline (V3)
- •Baclofen by intrathecal pump within 6 months (180 days) months at Baseline (V3)
- •Any previous history of deep brain stimulation or surgery intended to treat or correct cervical dystonia (e.g. myectomy)
- •Other treatments for cervical dystonia (anti-cholinergic, muscle relaxants such as flexeril or oral baclofen, or benzodiazepines) are allowed if the dose has been stable for ≥3 months (90 days).
- •Use of the following medications within 2 weeks prior to V3:
- •CYP3A inhibitors, inducers and substrates.
- •BCRP substrates: rosuvastatin, sulfasalazine
- •Use of the following food or beverages which might interact with MTR-601 within the last week prior to V3:
- •- Grapefruit juice or food products containing Seville orange extract (e.g. British orange marmalade, bitter orange liqueurs)
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, that, in the opinion of the Investigator, renders the participant unsuitable for the study.
- •Active neoplastic disease or history of any neoplastic disease within 5 years of screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care).
- •Active infection (e.g., sepsis, pneumonia, abscess) or a serious infection (e.g., resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to dosing.
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair are allowed).
- •Any of the following at screening (V2) (if any of these conditions are found on initial ECG, a repeat
- •ECG is allowed in consultation with the medical monitor):
- •QT interval corrected for heart rate using Fridericia's formula (QTcF), QRS duration, PR interval outside of normal limits confirmed by repeat measurement, unless deemed non-clinically significant by PI and agreed by Medical Monitor
- •Findings which would make QTc measurements difficult or QTc data uninterpretable
- •History of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)
- •Positive urine alcohol screen or positive urine drug screen (including amphetamines, cocaine, opiates, or barbiturates), at screening (V2).
- 另有 15 项未显示
排除标准
- 未提供
研究组 & 干预措施
MTR-601
80 mg during Weeks 1-2, 160 mg during Weeks 3-4 every day for 4 weeks
干预措施: MTR-601 (Drug)
Placebo
Matching placebo every day for 4 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of MTR-601 by the incidents of treatment-related adverse events as assessed by CTCAE v5.0
时间窗: Baseline to week 6
To evaluate the safety and tolerability of MTR-601 in participants with cervical dystonia by the incidents of treatments emergent adverse events
To evaluate the efficacy of MTR-601 in participants with cervical dystonia
时间窗: Baseline to week 4
To evaluate the efficacy of MTR-601 in participants with cervical dystonia by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) overall score change.
Safety and Tolerability of MTR-601 by the Incidents of Treatment-related Adverse Events as Assessed by CTCAE v5.0
时间窗: Baseline to week 6
Safety and tolerability of MTR-601 in participants with cervical dystonia by the incidents of treatments emergent adverse events
Efficacy of MTR-601 in Participants With Cervical Dystonia
时间窗: Baseline to week 4
Efficacy of MTR-601 in participants with cervical dystonia by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) overall score change. The overall score is a sum of three subscales consisting of Severity, Disability and Pain. The Overall score is a range of 0 to 85, with a higher value representing a worse outcome.
次要结局
- To evaluate the effect of MTR-601 on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity sub score(Baseline to week 2)
- To evaluate the plasma concentration of MTR-601 in participants with cervical dystonia overall and by age(Day 14 and Day 28)
- To evaluate the effect of MTR-601 on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) pain sub score(Baseline to week 2)
- To evaluate the effect of MTR-601 on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) disability sub score(Baseline to week 2)
- To evaluate the effect of MTR-601 on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) overall score(Baseline to week 2)
- Plasma Concentration of MTR-601 in Participants With Cervical Dystonia Overall(Day 14)
- Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Sub Score(Baseline and week 4)
- Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Sub Score(Baseline and week 4)
- Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Sub Score(Baseline and week 4)
- Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Overall Score(Baseline and week 2)
- Plasma Concentration of MTR-601 in Participants With Cervical Dystonia Overall(Day 28)
- Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Sub Score(Baseline and week 2)