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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04049097

Enrollment

121

Registered

2019-08-07

Start date

2019-05-20

Completion date

2021-11-15

Last updated

2023-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Inclusion Body Myositis

Keywords

IBM

Brief summary

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

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.

Interventions

DRUGArimoclomol

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

45 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score	Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).	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.

Secondary

Measure	Time frame	Description
Change in Modified Timed Up and Go (mTUG)	Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).	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 in Quadriceps Muscle Strength	Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).	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 in Six Minutes Walking Distance Test; Distance at 6 Minutes (6MWD)	Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).	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 in the 36-Item Short Form Health Survey (SF-36)	Change from Baseline in IBM-OLE to Early Termination Visit	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.
Number of Falls and Near Falls	Baseline to Early Termination Visit	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.
Change in Hand Grip Strength	Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).	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.

Countries

United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Arimoclomol (Open-label) Arimoclomol base 248 mg 3 times daily	121
Total	121

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	18
Overall Study	Death	2
Overall Study	Lost to Follow-up	1
Overall Study	Other	1
Overall Study	Physician Decision	2
Overall Study	Protocol Violation	2
Overall Study	The trial was terminated early by the sponsor	86
Overall Study	Withdrawal by Subject	9

Baseline characteristics

Characteristic	Arimoclomol (Open-label)
Age at diagnosis	62.3 years STANDARD_DEVIATION 8.02
Age, Continuous	66.2 years STANDARD_DEVIATION 7.91
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants
Race/Ethnicity, Customized Asian	3 Participants
Race/Ethnicity, Customized Black or African American	1 Participants
Race/Ethnicity, Customized Multiple	0 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants
Race/Ethnicity, Customized Other	2 Participants
Race/Ethnicity, Customized White	115 Participants
Sex: Female, Male Female	23 Participants
Sex: Female, Male Male	98 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	2 / 121
other Total, other adverse events	97 / 121
serious Total, serious adverse events	13 / 121

Outcome results

Primary

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.