Study of Arimoclomol in Inclusion Body Myositis (IBM)
- Registration Number
- NCT02753530
- Lead Sponsor
- ZevraDenmark
- Brief Summary
Funding Source - FDA Office of Orphan Products Development (OOPD). The purpose of this study is to evaluate the safety and efficacy of the study drug, arimoclomol in IBM patients.
- Detailed Description
A Phase 2/3, randomized, double-blind, placebo-controlled, international, 20-month intervention study in patients with IBM.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 152
- Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM.
- Demonstrate being able to arise from a chair without support from another person or device.
- Able to ambulate at least 20 ft/6 meters with or without assistive device. Once arisen from the chair, participant may use any walking device, i.e. walker/frame, can, crutches, or braces. They cannot be supported by another person and cannot use furniture or wall for support.
- Age at onset of weakness >45 years.
- Body weight of >= 40 kg.
- Able to give informed consent.
- History of any of the following excludes subject participation in the study: chronic infection particularly HIV or Hepatitis B or C; cancer other than basal cell cancer less than five years prior; or other chronic serious medical illnesses.
- Presence of any of the following on routine blood screening: White blood cells (WBC) <3000; platelets < 100,000; hematocrit <30%; blood urea nitrogen (BUN) >30 mg/dL; creatinine >1.5 x upper limit of normal; symptomatic liver disease with serum albumin <3 g/dL.
- History of most recent creatine kinase >15x the upper limit of normal without any other explanation besides IBM.
- History of non-compliance with other therapies.
- Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency.
- Coexistence of other disease that would be likely to affect outcome measures
- Drug or alcohol abuse within past three months.
- Participation in a recent drug study in the last 30 days prior to the screening visit or use of a biologic agent less than 6 months prior to the screening visit.
- Women who are lactating or unwilling to use adequate method of birth control who are not surgically sterile. Adequate birth control includes use of intrauterine device, abstinence, or oral contraceptives or a double barrier method, e.g condom plus diaphragm will be necessary for both male and female participants.
- Participants taking >7.5 mg prednisolone or equivalent or participants on Intravenous Immunoglobulin Therapy (IVIg) or other immunosuppressants within the last 3 months.
- Clinically significant renal or hepatic disease, as indicated by clinical laboratory assessment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 248 mg matching placebo 3 times daily Arimoclomol Arimoclomol 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily
- Primary Outcome Measures
Name Time Method Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score Change from Baseline to Month 20 Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person.
- Secondary Outcome Measures
Name Time Method Health Assessment Questionnaire - Disability Index (HAQ-DI) Change from Baseline to Month 12 and Month 20 The disability index of the HAQ measures self-reported functional status (disability) including the patient's use of aids or devices and/or help from other persons. The scale is composed of 20 items in 8 domains (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities). Each domain has at least 2 subcategory items, scored on a scale from 0 to 3, and for each of the 8 domains the domain score was the highest score of the involved subcategory scores. The total score reported is an average over 8 domains and scores from at least 6 domains had to be available for the total score to be calculated. The average total score ranges from 0 to 3, and a higher score corresponds to a worsening in functional status.
Falls and Near Falls Accumulated number from Baseline to Month 20 Falls and near falls registered by the participants in a diary
Modified Timed up and go (mTUG) Change from Baseline to Month 12 and Month 20 The patient's combined ability to rise from a chair and walk 3 meters, turn around and walk back to the chair and sit down. The test was performed twice and the fastest time was used. The results were expressed as velocity in meters/second.
Short Form-36 (SF-36) Mental Component Score Change from Baseline to Month 12 and Month 20 Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The mental component score is composed of energy/fatigue (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and emotional well-being (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status.
Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score Change from Baseline to Month 12 Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person.
Grip Strength Change from Baseline to Month 12 and 20 Unilateral hand grip strength in both hands measured using the Jamar Dynamometer. Results are for the stronger limb, as identified at baseline.
6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) Change from Baseline to Month 12 and Month 20 The distance patients could walk in 6 minutes. The distance walked in meters was recorded after 6 minutes.
Short Form-36 (SF-36) Physical Component Score Change from Baseline to Month 12 and Month 20 Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The physical component score includes 4 scales of physical functioning (10 items), role limitations due to physical health (4 items), bodily pain (2 items), and general health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status.
Patient Global Impression of Severity (PGIS) Change from Baseline to Month 12 and Month 20 Patient-reported assessment of the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing) at the time of the assessment. The response options for the impact of IBM were "none" (i.e. no impact), "very mild", "mild", "moderate", "severe", and "very severe".
Clinician Global Impression of Severity (CGIS) Change from Baseline to Month 12 and Month 20 Clinician-reported assessment of the severity of the patient's IBM symptoms at the time of the assessment. The response options were "none", "very mild", "mild", "moderate", "severe", and "very severe"
Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps Change from Baseline to Month 12 and Month 20 Unilateral strength of the knee extensor muscles on both limbs using the MicroFET hand-held dynamometer. Results are for the stronger limb, as identified at baseline.
Patient Global Impression of Change (PGIC) Change from Baseline to Month 12 and Month 20 Patient-reported assessment of the change from start of study treatment in the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing). The response options for change in impact were "very much worse", "much worse", "a little worse", "no change", "a little improved", "much improved", and "very much improved".
Clinician Global Impression of Change (CGIC) Change from Baseline to Month 12 and Month 20 Clinician-reported assessment of the change from start of study treatment in the patient's IBM symptoms. The response options for change in IBM were "very much worse", "much worse", "a little worse", "no change", "a little improved", "much improved", and "very much improved".
Manual Muscle Testing (MMT), Total Score Change from Baseline to Month 12 and Month 20 The Manual Muscle Testing (MMT) scores the strength of 24 muscles (axial, proximal, and distal muscles, tested bilaterally) on a scale from 0 to 10 points. The total score is calculated as an average across the 24 muscles and ranges from 0 to 10. The total score will increase if a patient is getting stronger and decrease if a patient is getting weaker.
2 Minute Walk Test (2MWT) Change from Baseline to Month 12 and Month 20 The distance patients could walk in 2 minutes (during the 6 Minute Walk Test) recorded in meters.
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Trial Locations
- Locations (12)
Phoenix Neurological Associates
🇺🇸Phoenix, Arizona, United States
University of California, Irvine
🇺🇸Irvine, California, United States
University of Colorado School of Medicine
🇺🇸Aurora, Colorado, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Rochester
🇺🇸Rochester, New York, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Nerve and Muscle Center of Texas
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Scroll for more (2 remaining)Phoenix Neurological Associates🇺🇸Phoenix, Arizona, United States