Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial

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

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)

Study Overview

• Status: Terminated
• Conditions: Inclusion Body Myositis
• Intervention / Treatment: Drug: Arimoclomol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • University College of London
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Neurological Associates
  • California
    • Irvine, California, United States, 92697
      • University of California
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University Of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Ohio
    • Columbus, Ohio, United States, 43221
      • The Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • Nerve and Muscle Center of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures.
2. Patient has completed the IBM4809 trial on treatment with Investigational Medicinal Product (IMP).

Exclusion Criteria:

1. Known or suspected allergy or intolerance to arimoclomol or its constituents.
2. 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.
3. Significant protocol deviation in the blinded IBM4809 trial based on the investigator's judgement in discussion with the medical monitor.

4. 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).
5. Any concurrent condition that in the investigator's opinion will significantly interfere with assessment of safety or efficacy.
6. Inability to comply with the protocol-specified procedures/evaluations and scheduled visits as per the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arimoclomol; 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily	Drug: Arimoclomol; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAEs) in the open label extension	Number of Treatment Emergent Adverse Events (TEAEs) in the open label extension	Baseline (start of OLE, week 0) to end of OLE (week 20)
Magnetic Resonance Imaging (MRI) whole fat fraction of the thigh		Change from Baseline to Month 20

Collaborators and Investigators

• Sponsor: ZevraDenmark
• Collaborators: University College, London; University of Kansas Medical Center
• Investigators: Principal Investigator: Mazen M Dimachkie, University Of Kansas Medical Center; Principal Investigator: Michael Hanna, University College, London

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2019
• Primary Completion (Actual): November 15, 2021
• Study Completion (Actual): November 15, 2021

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: IBM
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Myositis, Inclusion Body
• Other Study ID Numbers: IBM-OLE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No