Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial

Study Overview
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Brief Summary
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A multicenter, nonrandomized, open-label, uncontrolled clinical extension trial designed to compare the efficacy and safety of early versus delayed start of arimoclomol in the treatment of Inclusion Body Myositis (IBM)

Detailed Description
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This was planned to be a 40-month open-label extension trial of the 20-month randomized, double-blind, placebo-controlled IBM4809 trial. The open-label trial was terminated early by the sponsor as a consequence of the results of IBM4809 which did not meet any of its efficacy endpoints. Therefore, the actual average duration of open-label treatment was approximately 28 weeks.

Official Title
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An Open-label, Non-randomized Trial to Investigate the Efficacy and Safety of Early Versus Delayed Start of Arimoclomol in Patients With Sporadic Inclusion Body Myositis Who Have Completed the IBM4809 Trial

Conditions
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Inclusion Body Myositis

Intervention / Treatment
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* Drug: Arimoclomol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures. Patient has completed the IBM4809 trial on treatment with Investigational Medicinal Product (IMP). Exclusion Criteria: Known or suspected allergy or intolerance to arimoclomol or its constituents. Exposure to any other investigational treatment within 30 days or <5 half-lives of the baseline visit or taking part or planning to take part in another interventional trial. Significant protocol deviation in the blinded IBM4809 trial based on the investigator's judgement in discussion with the medical monitor. Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants up to 3 months after last dose. Premenopausal women must have a negative pregnancy test prior to dosing with trial medication. Acceptable methods of birth control are: Hormonal methods associated with inhibition of ovulation such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before arimoclomol administration. Total abstinence from sexual intercourse since the last menses before arimoclomol administration. (The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence [calendar, symptothermal, post-ovulation] methods are not acceptable methods of contraception). Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). Any concurrent condition that in the investigator's opinion will significantly interfere with assessment of safety or efficacy. Inability to comply with the protocol-specified procedures/evaluations and scheduled visits as per the investigator.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arimoclomol<br>248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily | Drug: Arimoclomol<br>* 2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily during breakfast, early afternoon, and at bedtime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | The Inclusion Body Myositis Functional Rating Scale (IBMFRS) 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), each 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. A higher score represents less functional limitation. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Six Minutes Walking Distance Test; Distance at 6 Minutes (6MWD) | Patients were instructed to walk down one side of a track and back along the opposite side as quickly and safely as possible for 6 minutes. Patients were allowed to take breaks as needed during the walking period, but timing continued during breaks. The distance walked in meters was recorded after 6 minutes. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). | 
| Change in Modified Timed Up and Go (mTUG) | The Modified Timed Up and Go (mTUG) measures the patient's ability to get up from a chair (allowing patients to use their arms), walk 3 meters, turn around, walk back to the chair, and sit down. The use of nearby walls or assistance from a caregiver was not allowed. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). | 
| Change in Quadriceps Muscle Strength | Maximal voluntary isometric contraction testing (MVICT) of the patient's quadriceps muscle (extensor strength of the knee) were performed using a hand myometer which is a hand-held device that allows the examiner to push against a muscle while the patient resists. The test was performed on each side. The results for the stronger knee are reported here. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). | 
| Change in Hand Grip Strength | Hand grip strength was assessed using a dynamometer. The test was performed on each hand. The grip strength of the stronger hand is reported here. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). | 
| Change in the 36-Item Short Form Health Survey (SF-36) | The 36-Item Short Form Health Survey (SF-36) is a 36-item, patient-reported survey of health status. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No derived scores were calculated for SF-36 and no summary tabulation was done. | Change from Baseline in IBM-OLE to Early Termination Visit | 
| Number of Falls and Near Falls | Patients recorded the number of falls and near falls in a falls diary. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No tabulation of falls and near falls was performed. | Baseline to Early Termination Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBM