Study of Arimoclomol in patients with Inclusion Body Myositis (IBM)

• Register: EUCTR
• Last refreshed on: 29 June 2020
• Main ID: EUCTR2017-004903-33-GB
• Date of registration: 05/04/2018
• Prospective Registration: Yes
• Primary sponsor: Orphazyme A/S
• Public title: Study of Arimoclomol in patients with Inclusion Body Myositis (IBM)
• Scientific title: Phase 2/3 Study of Arimoclomol in Inclusion Body Myositis (IBM) A Randomized, Double-blind, Placebo-Controlled Trial
• Date of first enrolment: 18/06/2018
• Target sample size: 150
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004903-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Clincial Department
• Affiliation: Orphazyme A/S

• Name: Clincial Department
• Affiliation: Orphazyme A/S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM.1 (as per Appendix 1 of the protocol)
2. Demonstrate being able to arise from a chair without support from another person or device
3. 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, cane, crutches, or braces. They cannot be supported by another person and cannot use furniture or wall for support.
4. Age at onset of weakness > 45 years
5. Body weight of > 40 kgs
6. Able to give informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion criteria:
1. 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.
2. Presence of any of the following on routine blood screening: WBC < 3000; platelets < 100,000; hematocrit < 30%; BUN > 30 mg; creatinine > 1.5 x upper limit of normal; symptomatic liver disease with serum albumin < 30mg/dl
3. History of most recent creatine kinase >15x the upper limit of normal without any other explanation besides IBM.
4. History of non-compliance with other therapies.
5. Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency.
6. Coexistence of any other disease that would likely to affect outcome measures.
7. Drug or alcohol abuse within past three months. Patient has recent history (within 6 months before Screening) of chronic alcohol or drug abuse which may compromise the patient’s safety or ability to participate in study activities. Cannabis for IBM symptoms will be allowed (where legal).
8. Participation in a recent drug study in the last 30 days prior to the screening visit or use of biologic agents less than 6 months prior to the screening visit.
9. Women who are lactating or pregnant, or sexually active female subjects of child-bearing potential* intending to become pregnant or unwilling to use a highly effective method of contraception** during the trial through 1 month after the last dose of trial medication. Sexually active males with female partners of child-bearing potential* unwilling to use a condom with or without spermicide in addition to the birth control used by their partners during the trial until 3 months after the last dose of trial medication unless surgically sterile (vasectomy).
Non child-bearing potential is defined as post-menopausal (minimum of 12 months with no menses and follicle-stimulating hormone in the post-menopausal range) or sterilisation (hysterectomy, oophorectomy, or bilateral tubal ligation).
** Highly effective methods of contraception include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; and vasectomised partner.
According to the recommendations from the Clinical Trial Facilitation Group (CTFG, 2014), sexual abstinence is considered a highly effective birth control method only if it is defined as refraining from heterosexual intercourse during the trial until 1 month after the last dose of trial medication (for female subjects of child-bearing potential) and for 3 months after the last dose of trial medication (for male subjects with female partners of child-bearing potential). The reliability of sexual abstinence needs to be evaluated by the investigator in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
10. Participants taking >7.5 mg prednisolone or equivalent or participants on intravenous immunoglobulin (IVIg) or other immunosuppressants within the last 3 months. Topical, nasal, and ocular corticosteroids are allowed unless they are being widely applied or

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Sporadic Inclusion Body Myositis (sIBM)
MedDRA version: 21.1 Level: LLT Classification code 10075052 Term: Sporadic inclusion body myositis System Organ Class: 100000004859

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Intervention(s)

Product Name: Arimoclomol
Product Code: BRX-345
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ARIMOCLOMOL
CAS Number: 368860-21-3
Current Sponsor code: BRX-345
Other descriptive name: Arimoclomol citrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy endpoint will be checked at Visit at Month 20

Main Objective: To evaluate the efficacy of arimoclomol at a daily dosage of 1200 mg (400 mg t.i.d) compared to placebo in the treatment of sporadic IBM at 20 months.

Primary end point(s): Primary efficacy endpoint is the change from baseline to Month 20 in the IBM Functional Rating Scale (IBMFRS) total score.

Secondary Objective:

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary endpoints will be checked as follows:
• IBMFRS total score: at every visit after the screening visit
• 6 minute walk test with 2 minute distance captured: at every clinical visit
• Modified Timed Up and Go (mTUG): at every clinical visit
• Muscle Strength Testing: at every clinical visit
• Health Assessment Questionnaire (HAQ-DI): at every clinical visit
• Grip strength using the Jamar device: at every clinical visit
• SF-36: at every clinical visit
• Falls and near falls: at every clinical visit
• PGIS and CGIS at all site visits,
• PGIC and CGIC at all post-baseline site visits (no PGI/CGI at Month1/Visit 3 or Month 2/Visit 4).

Safety endpoints will be checked at every visit

Secondary end point(s): Secondary efficacy endpoints will include changes from baseline over months 12 to 20 in the following measures of strength and function:
• IBMFRS total score (12 months)
• 6 minute walk test with 2 minute distance captured
• Modified Timed Up and Go (mTUG)
• Muscle Strength Testing
o Manual Muscle Testing (MMT)
o Isometric Contraction Testing of bilateral quadriceps strength using the MicroFET
• Health Assessment Questionnaire (HAQ-DI)
• Grip strength using the Jamar device
• SF-36
• Falls and near falls
• Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC)
• Clinician Global Impression of Severity (CGIS) and Clinician Global Impression of Change (CGIC)
• Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC)

Safety endpoints:
• Adverse events (AEs);
• Hematology;
• Clinical chemistry;
• Vital signs;
• Columbia Suicide Severity Rating Scale (C SSRS)

Secondary ID(s)

IBM4809

076773

NCT02753530

Source(s) of Monetary Support

Orphazyme A/S

Ethics review

Status: Approved
Approval date: 18/06/2018
Contact: