Inclusion Body MyositisPhase 3NCT04789070
Phase III Trial of Sirolimus in IBM
A Phase 3 study testing Sirolimus in people with Inclusion Body Myositis, run by University of Kansas Medical Center at 10 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Inclusion Body Myositis
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 1 Jul 2022to Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 31Show fewer
- 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:
- Total cholesterol > 8 mmol/l (304mg/dl)
- Triglycerides > 5 mmol/l (>194 mg/dl)
- Haemoglobin < 110 g/L (11g/dl)
- Platelet count < 100 x 109/L
- Neutrophils < 1.5 x 109/L
- Lymphocytes < 1.0 x 109/L
- 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;
- 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;
- 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);
- 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:
- Strong inhibitors of CYP3A4 and/or P-gp (eg ketoconazole, voriconazole, itraconazole, telithromycin, erythromycin or clarithromycin)
- Strong inducers of CYP3A4 and/or P-gp (eg rifampicin, rifabutin, Phenytoin, Phenobarbitol, St John's Wort);
- Use of any investigational drug other than study medication;
- Pregnancy or planning a pregnancy:
- 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.
- 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.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Australia7 sites
Royal Adelaide Hospital
Adelaide, South Australia
Royal Brisbane and Women's Hospital
Brisbane, Queensland
Austin Health
Melbourne, Victoria
St Vincent's Hospital
Melbourne, Victoria
Perron Institute
Perth, Washington
Concord Repatriation Hospital
Sydney, New South Wales
Royal Northshore Hospital
Sydney, New South Wales
United States2 sites
Johns Hopkins University
Baltimore, Maryland, 21218
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
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)
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
- Being tested
- Sirolimus, Placebo
- Medical subject headings
- Myositis, Inclusion Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Active comparator | 2mg capsules once daily Receives: Drug: Sirolimus |
| Placebo | Placebo comparator | 2mg capsules once daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 84
Secondary outcomes (3)
Change in 6 Minute Walk Test (6MWT) from Baseline to 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.
Measured: Baseline, Week 84
Change in Modified Timed Up and Go (mTUG) from Baseline to 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.
Measured: Baseline, Week 84
Change in Manual Muscle Testing (MMT) from Baseline to 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.
Measured: Baseline, Week 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start1 Jul 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inclusion Body MyositisStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Perron Institute
- Responsible party
- Sponsor
- Investigators
- Mazen Dimachkie, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04789070
- Sponsor's protocol ID
- Optimism in IBM
- Status last verified
- Jan 2026
- First submitted
- 15 Feb 2021
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40018746
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04789070
- Acronym / sponsor ID
- Optimism in IBM
- Conditions
- Inclusion Body Myositis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- The Perron Institute
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 9 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Active comparator | Drug: Sirolimus2mg capsules once daily |
| Placebo | Placebo comparator | Drug: Placebo2mg capsules once daily |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (31 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RapamuneSirolimus 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. | Drug | Sirolimus |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Change in 6 Minute Walk Test (6MWT) from Baseline to Week 84
Time frame: Baseline, Week 84
Change in Modified Timed Up and Go (mTUG) from Baseline to Week 84
Time frame: Baseline, Week 84
Change in Manual Muscle Testing (MMT) from Baseline to Week 84
Time frame: Baseline, Week 84
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Derived from this study: PubMed 40018746Badrising 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.
- Individual participant dataSharing planned: No
Related trials for Inclusion Body Myositis
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
Imaging Assessment of Swallowing and Speech Muscles in Inclusion Body Myositis
IBM, Inclusion Body Myositis
RecruitingObservational study
Adult and Juvenile Myositis
Dermatomyositis, Polymyositis
Not yet recruitingPhase 4
Emerging Indications for Hyperbaric Oxygen Treatment
Post-COVID-19 Condition, Ulcerative Colitis
Active, not recruitingObservational study
The Aim of the Study is to Characterize Patients Exhibiting Muscular Atrophy and Weakness Who Require a Muscle Biopsy for Diagnosis (IBM vs Atypical MND), Through an Innovative Technique Which Enables the Evaluation of the Neuromuscular Junction Involvement in Each Condition
Inclusion Body Myositis (IBM), Motor Neuron Disease, Amyotrophic Lateral Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mazen Dimachkie principal investigator
University of Kansas Medical Center
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Inclusion Body Myositis, run by University of Kansas Medical Center at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Australia, United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84 (time frame: Baseline, Week 84). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04789070, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.