2023-510317-26-00已完成2 期
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Assess the Efficacy, Safety, Tolerability, PK, and Biomarker Effects of PTC857 in Adult Subjects With Amyotrophic Lateral Sclerosis (CARDINALS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 242
- 试验地点
- 39
- 主要终点
- The primary endpoint is subject ranks based on the combined assessment of ALS Functional Rating Scale-Revised (ALSFRS-R) and survival after 24 weeks of treatment in the Intent-to-Treat 1 (ITT1) Analysis Set
研究概览
简要总结
To evaluate the efficacy of PTC857 in reducing disease progression in subjects with amyotrophic lateral sclerosis (ALS)
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Continued Long-Term Extension Period (Part C)
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Males or females aged between 18 and 80 years at the time of the initial Screening Visit
- •Females must refrain from ova (egg cell) donation from the start of the Screening Period through 90 days after the last dose of study drug
- •Males, if not surgically sterilized, with female partners of childbearing potential must agree to use barrier contraceptive (ie, condom) and their female partners must use a highly effective method of contraception from the start of the Screening Period through 90 days after the last dose of study drug
- •Males must refrain from sperm donations from the start of the Screening Period through 90 days after the last dose of the study drug
- •Willing and able to comply with all protocol procedures
- •ALS with preserved function, defined as: a. Onset of the first symptom leading to the diagnosis of ALS ≤24 months at the time of the initial Screening Visit b. Revised El Escorial criteria of either: (i) Clinically definite ALS (ii) Clinically probable ALS
- •A total ALSFRS-R score of at least 34 at the start of the Screening Period
- •No significant respiratory compromise as evidenced by slow vital capacity ≥60% at the start of the Screening Period (refer to the laboratory manual for specific requirements)
- •All chronic concomitant medications (both prescription and over the counter [OTC]) and non-pharmacologic therapy regimens, excluding standard-of-care therapy riluzole, edaravone, or sodium phenylbutyrate/taurursodiol (refer to inclusion criterion 13) should be stable and unchanged from 14 days prior to the start of the Screening Period and intend to remain stable and unchanged throughout the course of the study
- •Female subjects must have a negative breast cancer imaging screening status (not considered clinically abnormal and/or requiring further evaluation/treatment) within 6 months prior to the Screening Visit or during the Screening Period
- •Standard-of-care therapy for the treatment of ALS (riluzole, edaravone, or sodium phenylbutyrate/taurursodiol) should be stable and unchanged from 30 (-3) days prior to the start of the Screening Period and intend to remain stable and unchanged throughout the course of the study. Note: should a subject be discontinued from standard-of-care therapy due to removal of the therapy from the market, this will not be considered a protocol deviation.
- •Subjects or their designee (ie, legal authorized representative or caregiver) must understand the nature of the study and must provide signed and dated written informed consent prior to conducting any study-related procedures
- •Females must be either postmenopausal for ≥1 year (cessation of menses for 12 consecutive months) or surgically sterile (having undergone tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential and not abstinent, willing to use a highly effective method of contraception from the start of the Screening Period through 90 days after the last dose of study drug. Females who are abstinent will not be required to use a contraceptive method unless they become sexually active
排除标准
- •Females who are pregnant or nursing or plan to become pregnant during the study
- •For female subjects, any past medical history of breast cancer, regardless of remission status, or any first degree relative with history of breast cancer
- •History of allergies or adverse reactions to any of the excipients in the study drug formulation
- •Hepatic insufficiency, defined as liver function tests (LFTs) (ie, AST and/or ALT) ≥3× the upper limit of normal (ULN), or bilirubin ≥1.5× the ULN (except in the case of Gilbert’s disease)
- •Subject is taking a non-approved form of sodium phenylbutyrate and/or taurursodiol for the treatment of ALS
- •Moderate or worse renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min
- •History of alcohol or drug abuse within the last 6 months prior to the start of the Screening Period or current evidence of substance dependence
- •Any surgery within 30 days prior to the start of the Screening Period that may affect the subject’s ability to complete all study procedures
- •Subjects with clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular/ischemic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results
- •Any clinically significant medical or psychiatric condition or medical history that, in the opinion of the investigator or the medical monitor, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject
- •Current participation in any other investigational study with an investigational product or participation within 30 days prior to the start of the Screening Period or 5 half-lives of the previously taken investigational drug, whichever is longe
- •Subject has previously received PTC857
- •Subject is receiving a combination of edaravone and sodium phenylbutyrate/taurursodiol treatment, where applicable, within 30 (-3) days prior to the start of the Screening Period
结局指标
主要结局
The primary endpoint is subject ranks based on the combined assessment of ALS Functional Rating Scale-Revised (ALSFRS-R) and survival after 24 weeks of treatment in the Intent-to-Treat 1 (ITT1) Analysis Set
The primary endpoint is subject ranks based on the combined assessment of ALS Functional Rating Scale-Revised (ALSFRS-R) and survival after 24 weeks of treatment in the Intent-to-Treat 1 (ITT1) Analysis Set
次要结局
- Change from baseline in ALSFRS-R in the ITT1 Analysis Set after 24 weeks of treatment
- Safety and tolerability of PTC857 as measured by the severity and number of TEAEs and TESAEs, and change in clinical laboratory tests, physical examination, vital signs, Columbia-Suicide Severity Rating Scale (C-SSRS), and 12-lead electrocardiograms (ECGs) during the Treatment Period
- Change from baseline in slow vital capacity as assessed by pulmonary function tests (PFTs) after 24 weeks of treatment
- Change from baseline in motor/limb and bulbar function as assessed by the Modified Norris Scale after 24 weeks of treatment
- Subject ranks based on the combined assessment of ALSFRS-R and survival after 24 weeks of treatment in the Intent-to-Treat 2 (ITT2) Analysis Set
- Change from baseline in ALSFRS-R in the ITT2 Analysis Set after 24 weeks of treatment
- Survival as assessed by rate of and length of time to death
- Quality of life as assessed by ALSAQ-40 after 24 weeks of treatment
- Change from baseline in plasma NfL activity after 24 weeks of treatment
- Plasma PK and cerebrospinal fluid (CSF) exposure of PTC857
研究者
Aaron Tansy
Scientific
PTC Therapeutics Inc.
研究点 (39)
Loading locations...
相似试验
招募中
2 期
A Study to Evaluate the Long-term Safety and Effectiveness of APG777 in Subjects with Atopic DermatitisAtopic Dermatitis2024-519795-11-00Apogee Therapeutics Inc.79
招募中
2 期
Proof of Concept trial with CIT-013 in Rheumatoid Arthritis2024-517356-35-00Citryll B.V.77
招募中
2 期
A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of RO7268489 as Add-on Therapy to Ocrelizumab, in Participants With Progressive Forms of Multiple Sclerosis (MS)NCT07282574Hoffmann-La Roche360
招募中
3 期
AMX0035 and Progressive Supranuclear Palsy2023-505893-14-00Amylyx Pharmaceuticals Inc.269
招募中
3 期
Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor tolebrutinib (SAR442168) (PERSEUS)Primary Progressive Multiple Sclerosis2024-514495-41-00Genzyme Corp.487