Phase III Trial of Sirolimus in IBM

NCT04789070 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: Optimism in IBM
• Study Type: interventional
• Target: 140
• Locations: 3 countries
• Sites: 10

Brief Summary

The hypothesis is that Sirolimus, (Rapamycin (R)) which is currently used in organ transplantation and works by blocking the activity of T effector cells but preserving T regulatory cells, as well as by inducing autophagy (protein degradation), will be effective in IBM to slow or stabilize disease progression, helping to maintain patient function and independence. This phase III trial will confirm pilot data showing statistically significant clinical outcomes.

Conditions

Inclusion Body Myositis

Outcome Measures

Primary Outcomes (1)

• Change in IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84

  The IBM-FRS is a concise and quick (\~10 minute), clinician-administered ordinal rating scale used to determine participants' assessment of their capability and independence. It 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), 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, with a higher score representing less functional limitation.

  Baseline, Week 84

Secondary Outcomes (3)

• Change in 6 Minute Walk Test (6MWT) from Baseline to Week 84

  Baseline, Week 84

• Change in Modified Timed Up and Go (mTUG) from Baseline to Week 84

  Baseline, Week 84

• Change in Manual Muscle Testing (MMT) from Baseline to Week 84

  Baseline, Week 84

Study Arms (2)

Sirolimus

ACTIVE COMPARATOR

2mg capsules once daily

Drug: Sirolimus

Placebo

PLACEBO COMPARATOR

2mg capsules once daily

Drug: Placebo

Interventions

Sirolimus DRUG

Sirolimus is a currently licensed drug primarily used for immunosuppression post-kidney transplantation to prevent organ rejection. Sirolimus was initially considered as a treatment in IBM for its immunosuppressive action and beneficial effects in an experimental myositis mouse model.(11) Transfer of effector T cells from affected to healthy animals resulted in myositis, but the presence of Treg cells were protective against development of myositis. As Sirolimus, which acts to deplete effector T cells but preserving the Treg cells, was effective in this mouse model of myositis, it was therefore postulated that it may also be effective in IBM, not only for its effects on effector T cells and Treg cells, but also for its additional effects on protein degradation.

Also known as: Rapamune

Sirolimus

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults able to read and understand the Participant Information Sheet, and who freely provide written Informed Consent for the study;
• Males or females aged 45 years or older;
• Diagnosis of IBM according to the criteria proposed by the ENMC criteria 2011;
• Able to walk a minimum distance of 200m within 6 minutes (walking aids, including frames, may be used);
• Evidence of disease progression over the previous 12 months, as determined by a neuromuscular specialist through patient history, physical examination, MMT, IBM-FRS or other metrics.

You may not qualify if:

• Inability to complete a 6MWT with a minimum distance of 200m achieved;
• Inability to complete a mTUG or any other study procedure, including inability to swallow study drug, or clinical suspicion that the participant will become unable to swallow the study drug during the study period;
• Unwillingness or inability to comply with study interventions or study schedule;
• Hypersensitivity to Sirolimus, Everolimus or any compound of the oral solution;
• Any prior exposure to Sirolimus or Everolimus within the last 6 months;
• Presence of any other clinically significant disease that might interfere with patients ability to comply with study procedures, or places the patient at greater risk for SAEs;
• Clinical suspicion of moderate or severe respiratory insufficiency based on history, clinical examination or respiratory function tests with an FVC \< 50% of predicted; Nocturnal NIV is allowed for sleep-disordered breathing;
• Severe chronic kidney disease or renal insufficiency with proteinuria (e.g Estimated Glomerular Filtration Rate \< 30 ml/min and/or proteinuria as defined by spot urine protein/creatinine ratio \> 100mg/mmol;
• Chronic liver disease (cirrhosis and/or ALT/AST \> 3 times the upper limit of normal (ULN)) , excluding cases in which raised ALT/AST are deemed to be due to underlying muscle disease. Patients can be re-screened within the window if a one-off measurement is elevated due to an acute injury such as a viral infection;
• History of cancer (Except localised skin cancers including BCC/SCC) during the past 5 years;
• Systemic autoimmune or rheumatological disease not in remission and/or necessitating specific treatment during the last 12 months. This includes significant organ-specific autoimmune disorder (e.g Grave's disease) not in remission and/or necessitating specific treatment during the past 12 months;
• Any unhealed wounds or active infections at the time of screening;
• If patient has received a live vaccine within the last 12 weeks;
• Participants must be HIV negative, and Hepatitis C Virus Ribonucleic Acid (HCVRNA) Polymerase Chain Reaction (PCR) negative, and Hep B surface antigen negative and Hep B core antibody negative;
• One or more the following blood test results at screening:

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• The Perron Institute: collaborator

Study Sites (10)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Concord Repatriation Hospital

Sydney, New South Wales, Australia

Location

Royal Northshore Hospital

Sydney, New South Wales, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Austin Health

Melbourne, Victoria, Australia

Location

St Vincent's Hospital

Melbourne, Victoria, Australia

Location

Perron Institute

Perth, Washington, Australia

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Related Publications (1)

• Badrising UA, Henderson R, Reddel S, Corbett A, Liang C, Reardon K, Ghaoui R, Bulsara M, Brady S, Brusch A, Chan D, Coudert JD, Fairchild T, Jain G, Kiernan MC, Leonard D, Lloyd T, Schmidt J, McDermott MP, Sanders L, Lowe C, van der Kooi AJ, Weihl C, Mohassel P, Simpson M, Carroll A, Cooper I, Beer K, Hiscock K, Walters S, Panicker A, Doverty A, Heim A, van Heur-Neuman M, Benveniste O, Dimachkie MM, Needham M. Optimism in inclusion body myositis: a double-blind randomised controlled phase III trial investigating the effect of sirolimus on disease progression in patients with IBM as measured by the IBM Functional Rating Scale. Clin Exp Rheumatol. 2025 Feb;43(2):316-325. doi: 10.55563/clinexprheumatol/zvffa0. Epub 2025 Feb 26.

  PMID: 40018746 DERIVED

MeSH Terms

Conditions

Myositis, Inclusion Body

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Mazen Dimachkie

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2021
• First Posted: March 9, 2021
• Study Start: July 1, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); AU (7); NL (1)