An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of KL1333 (Napazimone) in Patients With Primary Mitochondrial Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 23
- 主要终点
- Adverse events
研究概览
简要总结
The purpose of this study is to investigate if the study medicine, KL1333, is safe, well-tolerated and effective long-term in improving the symptoms of fatigue and impacts on daily living and functional capacity (physical abilities) in people with PMD.
详细描述
This is a 12-month open-label extension (OLE) study to evaluate the safety, tolerability, and efficacy of KL1333 in subjects previously treated with KL1333 or placebo in Study KL1333-2020-104A (hereafter referred to as FALCON).
Subjects can be enrolled in this extension study either directly at the FALCON study completion visit (FALCON Week 48) or the safety follow-up visit (FALCON Week 53) or later in time. Subjects who previously received KL1333 in FALCON will receive retreatment whereas subjects previously treated with placebo will be treatment naïve to KL1333.
The study consists of a screening visit (if the subject rolls over directly from the FALCON study completion visit [FALCON Week 48] or the safety follow up visit [FALCON Week 53], the screening visit is coincident with the visit), a 48-week treatment course with KL1333 up to 100 mg/day, a completion visit (end of treatment; EoT) and approximately 5 weeks of follow up, including the end of study (EoS) visit. The treatment period may extend beyond 48 weeks until the study drug is commercially or otherwise available, in which case the EoT visit will occur later than Week 48. Periodic safety monitoring visits (phone visits every 4 weeks after Week 48 and clinic visits every 24 weeks after Week 48) will continue for subjects who receive KL1333 in the optional extended treatment period until the study drug is commercially or otherwise available.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed the FALCON study (age 18 years or older), and in the opinion of the investigator and sponsor has been compliant with the study requirements
- •Willingness and ability to attend study appointments within the specified time windows
- •Willingness and ability to complete electronic patient-reported outcomes
- •Concomitant medications likely to remain stable throughout participation in the study where clinically possible
- •Willingness to suspend treatment with idebenone during the study
排除标准
- •The subject is, in the investigator's opinion, unlikely to comply with the protocol, e.g., due to cognitive impairment, or is unsuitable for any reason.
- •Any medical, psychiatric, laboratory or other condition that may negatively affect the benefit-risk considerations of study participation or interfere with the interpretation of study results and, in the judgment of the investigator and/or the medical monitor, would make the subject inappropriate for entry into this study.
- •Subjects not enrolling directly at the FALCON study completion visit (FALCON Week 48) or the safety follow-up visit (FALCON Week 53) study will be required to fulfill the additional exclusion criteria below during the screening visit:
- •General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.
研究组 & 干预措施
Open label extension
Subjects will receive medication twice a day for 48 weeks minimum
干预措施: Napazimone (Drug)
结局指标
主要结局
Adverse events
时间窗: Through study at least for 48 weeks
Number of adverse events will be monitored throughout the study for all subjects
Physical examination
时间窗: At Baseline Week 0, Week 4, Week 24 and Week 48
The following parameters and body systems will be examined and any abnormalities described: height and weight; general appearance; skin; head, ears, eyes, nose, and throat; lungs; heart; lower extremity examination; abdomen; neurologic and lymph nodes. Any clinically significant changes from baseline should be recorded as AEs.
Vital signs
时间窗: At Baseline Week 0, Week 4, Week 24 and Week 48
Body temperature, systolic and diastolic cuff blood pressure, pulse rate and pulse oximetry will be measured and any clinically significant changes from baseline should be recorded as AEs.
Electrocardiogram
时间窗: At Baseline Week 0, Week 4, Week 24 and Week 48
Changes from baseline of ECG parameters will be evaluated.
Safety laboratory - blood chemistry
时间窗: At Baseline Week 0, Week 4, Week 24 and Week 48
Monitoring of the clinically significant laboratory results for sodium, potassium, chloride, bicarbonate/carbon dioxide;, blood urea nitrogen, serum creatinine, glucose, albumin, total protein, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, calcium, gamma-glutamyl transferase, creatine kinase
Safety laboratory - urinalysis
时间窗: At Baseline Week 0, Week 4, Week 24 and Week 48
Monitoring of the clinically significant laboratory results for specific gravity, pH, semi-quantitative "dipstick" evaluation of glucose, protein, bilirubin, ketones, leukocytes, blood microscopy and/or culture to be performed if clinically indicated or if urinalysis results positive.
Safety laboratory - hematology
时间窗: At Baseline Week 0, Week 4, Week 24 and Week 48
Monitoring of the clinically significant laboratory results for Hemoglobin, hematocrit, white blood cell with differentials (monocytes, eosinophils, basophils, neutrophils, lymphocytes) as an absolute value, red blood cell count, platelet count, C-reactive protein
Occurence of metabolic decompensation and lactic acidosis or image-verified stroke-like episodes consequent to GI AE and AESIs
时间窗: Through study at least for 48 weeks
These events will be monitored throughout the study.
Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: At Baseline Week 0
C-SSRS assesses suicidal ideation and behavior risk through a series of questions to assess for suicidal ideation and behavior, the severity and immediacy of the risk, and the level of support the subject may need. C-SSRS Severity of Ideation scores of 4 or 5 are considered SAEs.
次要结局
- Patient-reported mitochondrial fatigue(Through study at least for 48 weeks)
- Functional outcome(At Baseline Week 0, Week 4, Week 24 and Week 48)
- Patient-reported lower extremity function(At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48)
- Other patient-reported outcome - Patient Global Impression (multiple)(At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48)
- Other patient-reported outcomes - 5-level EuroQol-5 Dimension(At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48)
- Global impression of severity of PMD disease expression(At Baseline Week 0, Week 24 and Week 48)
- Assessments of mitochondrial disease progression(At Baseline Week 0, Week 24 and Week 48)
- Mitochondrial diabetes, subgroup analysis(At Baseline Week 0, Week 24 and Week 48)