A Double-Blind Randomised Controlled Trial (dbRCT) Phase III Trial Investigating the Effect of Sirolimus on Disease Progression in Patients With Inclusion Body Myositis (IBM) as Measured by the IBM Functional Rating Scale (IBM-FRS)
概览
- 阶段
- 3 期
- 干预措施
- Sirolimus
- 疾病 / 适应症
- Inclusion Body Myositis
- 发起方
- University of Kansas Medical Center
- 入组人数
- 140
- 试验地点
- 10
- 主要终点
- Change in IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
The hypothesis is that Sirolimus, (Rapamycin (R)) which is currently used in organ transplantation and works by blocking the activity of T effector cells but preserving T regulatory cells, as well as by inducing autophagy (protein degradation), will be effective in IBM to slow or stabilize disease progression, helping to maintain patient function and independence. This phase III trial will confirm pilot data showing statistically significant clinical outcomes.
研究者
入排标准
入选标准
- •Adults able to read and understand the Participant Information Sheet, and who freely provide written Informed Consent for the study;
- •Males or females aged 45 years or older;
- •Diagnosis of IBM according to the criteria proposed by the ENMC criteria 2011;
- •Able to walk a minimum distance of 200m within 6 minutes (walking aids, including frames, may be used);
- •Evidence of disease progression over the previous 12 months, as determined by a neuromuscular specialist through patient history, physical examination, MMT, IBM-FRS or other metrics.
排除标准
- •Inability to complete a 6MWT with a minimum distance of 200m achieved;
- •Inability to complete a mTUG or any other study procedure, including inability to swallow study drug, or clinical suspicion that the participant will become unable to swallow the study drug during the study period;
- •Unwillingness or inability to comply with study interventions or study schedule;
- •Hypersensitivity to Sirolimus, Everolimus or any compound of the oral solution;
- •Any prior exposure to Sirolimus or Everolimus within the last 6 months;
- •Presence of any other clinically significant disease that might interfere with patients ability to comply with study procedures, or places the patient at greater risk for SAEs;
- •Clinical suspicion of moderate or severe respiratory insufficiency based on history, clinical examination or respiratory function tests with an FVC \< 50% of predicted; Nocturnal NIV is allowed for sleep-disordered breathing;
- •Severe chronic kidney disease or renal insufficiency with proteinuria (e.g Estimated Glomerular Filtration Rate \< 30 ml/min and/or proteinuria as defined by spot urine protein/creatinine ratio \> 100mg/mmol;
- •Chronic liver disease (cirrhosis and/or ALT/AST \> 3 times the upper limit of normal (ULN)) , excluding cases in which raised ALT/AST are deemed to be due to underlying muscle disease. Patients can be re-screened within the window if a one-off measurement is elevated due to an acute injury such as a viral infection;
- •History of cancer (Except localised skin cancers including BCC/SCC) during the past 5 years;
研究组 & 干预措施
Sirolimus
2mg capsules once daily
干预措施: Sirolimus
Placebo
2mg capsules once daily
干预措施: Placebo
结局指标
主要结局
Change in IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84
时间窗: Baseline, Week 84
The IBM-FRS is a concise and quick (\~10 minute), clinician-administered ordinal rating scale used to determine participants' assessment of their capability and independence. It includes 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs), graded on a Likert scale from 0 (being unable to perform) to 4 (normal). The sum of the 10 items gives a value between 0 and 40, with a higher score representing less functional limitation.
次要结局
- Change in 6 Minute Walk Test (6MWT) from Baseline to Week 84(Baseline, Week 84)
- Change in Manual Muscle Testing (MMT) from Baseline to Week 84(Baseline, Week 84)
- Change in Modified Timed Up and Go (mTUG) from Baseline to Week 84(Baseline, Week 84)