Arimoclomol for inclusion body myositis (IBM)

ISRCTN	ISRCTN80057573
DOI	https://doi.org/10.1186/ISRCTN80057573
EudraCT/CTIS number	2008-008208-42
ClinicalTrials.gov number	NCT00769860
Secondary identifying numbers	7748

Submission date: 02/02/2011
Registration date: 02/02/2011
Last edited: 04/10/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Ms Gisela Barreto
Scientific

Centre for Neuromuscular Diseases
Queen Square
London
WC1N 3BG
United Kingdom

Email	Gisela.Barreto@uclh.nhs.uk

Study information

Study design	Randomised multicentre interventional treatment trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A randomised, double blinded, placebo-controlled pilot study assessing the safety and tolerability of arimoclomol in adult patients with inclusion body myositis
Study hypothesis	Sporadic inclusion body myositis (IBM) is the commonest muscle disease acquired by those aged over 50 years. Nevertheless, despite being the subject of several clinical trials, it remains without any proven treatment. This study seeks to make the first assessment of a novel therapeutic compond, arimoclomol, in IBM. This is the first potential treatment of IBM not to target purely inflammation. The primary objective of this proposed study is to assess the safety and tolerability of arimiclomol (100 mg three times a day [TDS]). The secondary objective is to determine whether arimoclomol has its anticipated pharmaceutical action to augment the concentration of key heat shock proteins (HSPs) in muscle tissue of IBM patients. The further objective is to evaluate a framework of clinical assessment, including measures of muscle strength, which can be used for subsequent practical and statistical planning of a larger future study of efficacy. The study will include 12 patients with IBM, 8 of whom will receive arimoclomol and 4 a matching placebo over 4 months. The primary outcome measure will be adverse event reporting. Secondary outcome measures will include muscle strength testing (by manual muscle testing and myometry), muscle mass measure (DEXA), IBM functional rating scale, and muscle biopsies pre- and post-treatment to measure levels of HSP70, and to assess pathological changes in muscle fibres. More details can be found here: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7748
Ethics approval(s)	The Joint UCL/UCLH Committees on the Ethics of Human Research (committee A) - currently Central London REC 4 - approved (ref: 09/H0714/22)
Condition	Topic: Musculoskeletal; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal
Intervention	Twelve subjects will be randomised to one of two groups: placebo (4 patients) or Arimoclomol 100 mg three times daily (TDS) (8 patients). Participants will receive study medication for 4 months. During the treatment trial patients will be seen at screening, day 0 (baseline) and months 0.4, 1, 1.5, 2, 2.5, 3, 3.5 and 4. After the 4 month drug treatment trial, patients will be followed monthly for 8 months in order to obtain clinical endpoint measures for a total of 12 months. Muscle biopsies will be obtained at baseline (day 0) and month 4. Follow-up length: 8 months Study entry: registration and one or more randomisations
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Arimiclomol
Primary outcome measure	Adverse events, measured throughout the study
Secondary outcome measures	1. Muscle strength testing (by manual muscle testing and myometry) 2. Muscle mass measures (by DEXA scans) 3. IBM functional rating scale 4. Pre- and post-treatment concentrations of HSP70 5. Pathological changes in muscle fibres
Overall study start date	01/10/2010
Overall study end date	01/10/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	Planned sample size: 24; UK sample size: 12
Participant inclusion criteria	1. Meet the diagnostic criteria for definite or probable inclusion body myositis (IBM) (Griggs 1995) 2. Muscle function adequate for quantitative muscle testing. At least 8 of the following 16 muscle groups have a Manual Muscle Test (MMT) Grade greater than 3, or greater on the modified Medical Research Council Scale 3. Aged greater than 50 years, either sex 4. Women must be post-menopausal (no menses in greater than 12 months) or status post-hysterectomy
Participant exclusion criteria	1. Presence of any one of the following medical conditions: 1.1. Diabetes mellitus or patients taking anti-diabetic medications 1.2. Chronic infection 1.3. Chronic renal insufficiency 1.4. Cancer other than skin cancer less than 5 years previously 1.5. Multiple sclerosis or prior episode of central nervous system demyelination 1.6. Other chronic serious medical illnesses 2. Presence of any of the following on routine blood screening: 2.1. White blood cell count (WBC) less than 300/cm3 2.2. Platelets less than 100,000/cm3 2.3. Haematocrit less than 30% 2.4. Urea greater than 10 mmol/l 2.5. Creatinine greater than 150 µmol/l 2.6. Symptomatic liver disease with serum albumin less than 30 g/l 2.7. Prothrombin time or activated partial thromboplastin greater than upper range of control values 3. Currently taking riluzole 4. Women who are pregnant or lactating 5. History of non-compliance with other therapies 6. Coexistence of other neuromuscular disease 7. Drug or alcohol abuse within last 3 months 8. Inability to give informed consent 9. Known bleeding disorder (e.g. haemophilia, Von Willebrand's Disease) 10. Use of potentially nephrotoxic drugs 11. Prior difficulties with local anaesthetic
Recruitment start date	01/10/2010
Recruitment end date	01/10/2012

Locations

Countries of recruitment

England
United Kingdom
United States of America

Study participating centre

National Hospital for Neurology and Neurosurgery

London
WC1N 3BG
United Kingdom

Sponsor information

University College London (UCL) (UK)
University/education

UCL Biomedicine Research and Development Unit
Maple House
149 Tottenham Court Road
London
W1T 7NF
England
United Kingdom

Website	http://www.ucl.ac.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Charity

Arthritis Research UK
Private sector organisation / Other non-profit organizations

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	23/03/2016		Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

04/10/2017: Publication reference added.