Phase III Trial of Sirolimus in IBM

Last updated: February 12, 2025
Sponsor: University of Kansas Medical Center
Overall Status: Active - Not Recruiting

Phase

3

Condition

Myositis

Polymyositis (Inflammatory Muscle Disease)

Idiopathic Inflammatory Myopathies

Treatment

Sirolimus

Placebo

Clinical Study ID

NCT04789070
Optimism in IBM
  • Ages > 45
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Adults able to read and understand the Participant Information Sheet, and who freelyprovide written Informed Consent for the study;

  2. Males or females aged 45 years or older;

  3. Diagnosis of IBM according to the criteria proposed by the ENMC criteria 2011;

  4. Able to walk a minimum distance of 200m within 6 minutes (walking aids, includingframes, may be used);

  5. Evidence of disease progression over the previous 12 months, as determined by aneuromuscular specialist through patient history, physical examination, MMT, IBM-FRSor other metrics.

Exclusion

Exclusion Criteria:

  1. Inability to complete a 6MWT with a minimum distance of 200m achieved;

  2. Inability to complete a mTUG or any other study procedure, including inability toswallow study drug, or clinical suspicion that the participant will become unable toswallow the study drug during the study period;

  3. Unwillingness or inability to comply with study interventions or study schedule;

  4. Hypersensitivity to Sirolimus, Everolimus or any compound of the oral solution;

  5. Any prior exposure to Sirolimus or Everolimus within the last 6 months;

  6. Presence of any other clinically significant disease that might interfere withpatients ability to comply with study procedures, or places the patient at greaterrisk for SAEs;

  7. 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;

  8. Severe chronic kidney disease or renal insufficiency with proteinuria (e.g EstimatedGlomerular Filtration Rate < 30 ml/min and/or proteinuria as defined by spot urineprotein/creatinine ratio > 100mg/mmol;

  9. 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 underlyingmuscle disease. Patients can be re-screened within the window if a one-offmeasurement is elevated due to an acute injury such as a viral infection;

  10. History of cancer (Except localised skin cancers including BCC/SCC) during the past 5 years;

  11. Systemic autoimmune or rheumatological disease not in remission and/or necessitatingspecific treatment during the last 12 months. This includes significantorgan-specific autoimmune disorder (e.g Grave's disease) not in remission and/ornecessitating specific treatment during the past 12 months;

  12. Any unhealed wounds or active infections at the time of screening;

  13. If patient has received a live vaccine within the last 12 weeks;

  14. Participants must be HIV negative, and Hepatitis C Virus Ribonucleic Acid (HCVRNA)Polymerase Chain Reaction (PCR) negative, and Hep B surface antigen negative and HepB core antibody negative;

  15. One or more the following blood test results at screening:

  16. Total cholesterol > 8 mmol/l (304mg/dl)

  17. Triglycerides > 5 mmol/l (>194 mg/dl)

  18. Haemoglobin < 110 g/L (11g/dl)

  19. Platelet count < 100 x 109/L

  20. Neutrophils < 1.5 x 109/L

  21. Lymphocytes < 1.0 x 109/L

  22. Presence at screening of any medically significant cardiac, neurological, pulmonary,gastrointestinal, musculoskeletal or psychiatric illness (including uncontrolledanxiety and/or depression) that in the Investigator's opinion might interfere withthe patient's ability to comply with study procedures or that might confound theinterpretation of clinical safety or IBM-FRS;

  23. Has taken any investigational study drug within 30 days or five half-lives of theprior agent (whichever is longer) prior to the Baseline visit;

  24. Patient taking any other immunosuppressive or immunomodulatory medication (includingbut not limited to prior high dose prednisolone (>10mg/day) in the last 4 weeks,Intravenous Immunoglobulin (IVIG) within the last 3 months, methotrexate,mycophenolate, Sirolimus, Everolimus, calcineurin inhibitors, (cyclosporine ortacrolimus) or azathioprine within the last 6 months, and rituximab, alemtuzumab orother biologics within the last 12 months);

  25. Other medications or products that may affect the metabolism of Sirolimus (Seeconcomitant medications in Section 27) such as the following at time of screening:

  26. Strong inhibitors of CYP3A4 and/or P-gp (eg ketoconazole, voriconazole,itraconazole, telithromycin, erythromycin or clarithromycin)

  27. Strong inducers of CYP3A4 and/or P-gp (eg rifampicin, rifabutin, Phenytoin,Phenobarbitol, St John's Wort);

  28. Use of any investigational drug other than study medication;

  29. Pregnancy or planning a pregnancy:

  30. Women of child-bearing potential (WOCBP) must have a negative serum pregnancytest prior to randomisation, and must have a negative urine pregnancy testwithin 24 hours prior to the start of study drug. WOCBP must agree to use 'highly effective' contraception (MHRA guidelines, 2014) for the duration ofthe study and for 12 weeks post-treatment completion.

  31. Men who are sexually active with a WOCBP must agree to use barriercontraception (condom) for the duration of treatment with study drug and for 30days post-treatment completion.

Study Design

Total Participants: 140
Treatment Group(s): 2
Primary Treatment: Sirolimus
Phase: 3
Study Start date:
July 01, 2022
Estimated Completion Date:
December 01, 2026

Connect with a study center

  • Concord Repatriation Hospital

    Sydney, New South Wales
    Australia

    Site Not Available

  • Royal Northshore Hospital

    Sydney, New South Wales
    Australia

    Site Not Available

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland
    Australia

    Site Not Available

  • Royal Adelaide Hospital

    Adelaide, South Australia
    Australia

    Site Not Available

  • Austin Health

    Melbourne, Victoria
    Australia

    Site Not Available

  • St Vincent's Hospital

    Melbourne, Victoria
    Australia

    Site Not Available

  • Perron Institute

    Perth, Washington
    Australia

    Site Not Available

  • University of Kansas Medical Center

    Kansas City, Kansas 66160
    United States

    Site Not Available

  • Johns Hopkins University

    Baltimore, Maryland 21218
    United States

    Site Not Available

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