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Phase III Trial of Sirolimus in IBM

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04789070
Recruitment Status : Recruiting
First Posted : March 9, 2021
Last Update Posted : April 13, 2023
The Perron Institute
Information provided by (Responsible Party):
University of Kansas Medical Center

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.

Condition or disease Intervention/treatment Phase
Inclusion Body Myositis Drug: Sirolimus Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Randomised Controlled Trial (dbRCT) Phase III Trial Investigating the Effect of Sirolimus on Disease Progression in Patients With Inclusion Body Myositis (IBM) as Measured by the IBM Functional Rating Scale (IBM-FRS)
Actual Study Start Date : July 1, 2022
Estimated Primary Completion Date : February 1, 2024
Estimated Study Completion Date : February 1, 2024

Arm Intervention/treatment
Active Comparator: Sirolimus
2mg capsules once daily
Drug: Sirolimus
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.
Other Name: Rapamune

Placebo Comparator: Placebo
2mg capsules once daily
Drug: Placebo

Primary Outcome Measures :
  1. Change in IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84 [ Time Frame: Baseline, 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.

Secondary Outcome Measures :
  1. Change in 6 Minute Walk Test (6MWT) from Baseline to Week 84 [ Time Frame: Baseline, Week 84 ]
    The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The 6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance in patients with cardiopulmonary disease. It is now a commonly used and validated test to estimate the functional walking capacity in patients with a range of chronic diseases including IBM.

  2. Change in Modified Timed Up and Go (mTUG) from Baseline to Week 84 [ Time Frame: Baseline, Week 84 ]
    The Timed Up and Go (mTUG) was initially developed as a tool to determine falls risk, mobility, balance and walking ability in an elderly population. It has since been adopted as an outcome measure in a broader clinical setting including myositis.

  3. Change in Manual Muscle Testing (MMT) from Baseline to Week 84 [ Time Frame: Baseline, Week 84 ]
    Manual Muscle Testing (MMT) is a relatively simple method of assessing a patient's strength in a muscle or group of muscles. There is however a degree of subjectivity when assigning a score. MMT will be used to assess change in strength throughout the study period. This method is routinely performed in a clinical setting and has been shown to be reliable. This tool assesses muscle strength using a 0 - 10 point scale.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Adults able to read and understand the Participant Information Sheet, and who freely provide 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, including frames, may be used);
  5. 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.

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 to swallow study drug, or clinical suspicion that the participant will become unable to swallow 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 with patients ability to comply with study procedures, or places the patient at greater risk 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 Estimated Glomerular Filtration Rate < 30 ml/min and/or proteinuria as defined by spot urine protein/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 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;
  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 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;
  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 Hep B core antibody negative;
  15. One or more the following blood test results at screening:

    1. Total cholesterol > 8 mmol/l (304mg/dl)
    2. Triglycerides > 5 mmol/l (>194 mg/dl)
    3. Haemoglobin < 110 g/L (11g/dl)
    4. Platelet count < 100 x 109/L
    5. Neutrophils < 1.5 x 109/L
    6. Lymphocytes < 1.0 x 109/L
  16. Presence at screening of any medically significant cardiac, neurological, pulmonary, gastrointestinal, musculoskeletal or psychiatric illness (including uncontrolled anxiety and/or depression) that in the Investigator's opinion might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or IBM-FRS;
  17. Has taken any investigational study drug within 30 days or five half-lives of the prior agent (whichever is longer) prior to the Baseline visit;
  18. Patient taking any other immunosuppressive or immunomodulatory medication (including but 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 or tacrolimus) or azathioprine within the last 6 months, and rituximab, alemtuzumab or other biologics within the last 12 months);
  19. Other medications or products that may affect the metabolism of Sirolimus (See concomitant medications in Section 27) such as the following at time of screening:

    1. Strong inhibitors of CYP3A4 and/or P-gp (eg ketoconazole, voriconazole, itraconazole, telithromycin, erythromycin or clarithromycin)
    2. Strong inducers of CYP3A4 and/or P-gp (eg rifampicin, rifabutin, Phenytoin, Phenobarbitol, St John's Wort);
  20. Use of any investigational drug other than study medication;
  21. Pregnancy or planning a pregnancy:

    1. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to randomisation, and must have a negative urine pregnancy test within 24 hours prior to the start of study drug. WOCBP must agree to use 'highly effective' contraception (MHRA guidelines, 2014) for the duration of the study and for 12 weeks post-treatment completion.
    2. Men who are sexually active with a WOCBP must agree to use barrier contraception (condom) for the duration of treatment with study drug and for 30 days post-treatment completion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04789070

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Contact: Andrew J Heim 9139459926

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United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Ali Ciersdorff   
Principal Investigator: Mazen Dimachkie, MD         
United States, Maryland
Johns Hopkins University Not yet recruiting
Baltimore, Maryland, United States, 21218
Contact: Ellen Eline   
Principal Investigator: Thomas Lloyd         
Australia, New South Wales
Concord Repatriation Hospital Not yet recruiting
Sydney, New South Wales, Australia
Contact: Alison Craig   
Principal Investigator: Stephen Reddel         
Royal Northshore Hospital Not yet recruiting
Sydney, New South Wales, Australia
Contact: Sharon Leaver   
Principal Investigator: Christina Liang         
Australia, Queensland
Royal Brisbane and Women's Hospital Not yet recruiting
Brisbane, Queensland, Australia
Contact: Kathryn Thorpe   
Principal Investigator: Robert Henderson         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia
Contact: Helen Birkin   
Principal Investigator: Roula Ghaoui         
Australia, Victoria
Austin Health Not yet recruiting
Melbourne, Victoria, Australia
Contact: Elise Heriot   
Principal Investigator: Gayatri Jain         
St Vincent's Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Iveta Krivonos   
Principal Investigator: Katrina Reardon         
Australia, Western Australia
Perron Institute Recruiting
Perth, Western Australia, Australia
Contact: Kelly Beer   
Principal Investigator: Merrilee Needham, MD         
Sponsors and Collaborators
University of Kansas Medical Center
The Perron Institute
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Principal Investigator: Mazen Dimachkie University of Kansas Medical Center
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Responsible Party: University of Kansas Medical Center Identifier: NCT04789070    
Other Study ID Numbers: Optimism in IBM
First Posted: March 9, 2021    Key Record Dates
Last Update Posted: April 13, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Myositis, Inclusion Body
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs