Ruxolitinib Treatment in Inclusion Body Myositis

Phase 2

Not yet recruiting

• Conditions: Inclusion Body Myositis, Sporadic
• Interventions: Drug: Ruxolitinib; Drug: Placebo

• Registration Number: NCT06536166
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Refer to the "Detailed Description" section.

Detailed Description

A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of Ruxolitinib in the Treatment of Subjects with Inclusion Body Myositis (IBM) IBM is the most frequent idiopathic immune myopathy (IIM) over age 45, pathologically characterized by the combination of intramuscular inflammation and degenerative...

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-26
• Study First Submitted QC: 2024-07-31
• Last Update Submitted: 2024-07-31
• Study First Posted: 2024-08-02
• Last Update Posted: 2024-08-02
• Study Start: 2025-01-01
• Primary Completion: 2028-01-15
• Study Completion: 2028-04-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Age ≥ 45 years
• Effective contraception for the duration of the clinical trial for fertile women of childbearing age
• Defined diagnosis of IBM according to data-derived criteria (Llyod et al, 2014): Patient must fulfill the three following criteria for being diagnosed as IBM: (1) finger flexor or quadriceps weakness; and (2) muscle biopsy showing endomysial inflammation; and (3) muscle biopsy showing invasion of nonnecrotic muscle fibers or rimmed vacuoles
• To be able to walk 6 min without assistance from another person (external assist devices permitted [e.g., canes, walkers, or rollators])
• Patient informed and having signed the consent for participation, possibly assisted by a trusted person

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Exclusion Criteria

• Pregnancy or breastfeeding

• Patient under guardianship, curatorship, safeguard of justice or deprived of liberty

• Patient with cognitive disorders or unable, according to the investigator, to understand the study and/or to give informed consent

• Quadriceps weakness (manual muscle testing, MRC) below or equal 1

• FVC or forced expiratory volume (FEV) < 50% of predicted value

• Concomitant use of immunomodulatory drugs including previous treatment with JAK inhibitor, or medications acting on muscle anabolism or catabolism

• Live vaccine within the 4 weeks before starting ruxolitinib therapy

• Comorbidity or active chronic disease which contraindicate ruxolitinib:

  • Current active infections including Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Viruses, tuberculosis or history of active HIV infection or tuberculosis (cured infection by HBV or HCV does not counter-indicate ruxolitinib)

  • Symptomatic herpes simplex infection at baseline or history of symptomatic herpes simplex infection within 12 weeks prior to baseline; in case of active Varicella-Zoster Virus (VZV) infection (herpes zoster or shingles) the inclusion is possible after its resolution under antiviral treatment (e.g. acyclovir, valaciclovir). If preventive treatment seems necessary (previous episodes of zona), anti-VZV recombinant vaccine Shingrix™ may be administered before inclusion.

  • The lack of specialist's approval in the following cases:

    • Cardiologist's approval in case of recent history (<6 months) of cardiovascular or thromboembolic disease (documented coronaropathy or hospitalization for acute arterial thrombosis or stroke or deep venous thrombosis or pulmonary embolism). Anti-platelet aggregation drug (aspirin) can be associated to ruxolitinib if investigator deems it necessary.
    • Oncologist's approval in case of active smoking more than 20 pack-years or recent history (<6 months) of neoplastic disease (especially skin cancers)

  • Very high cardiovascular risk (red color) at SCORE 2 in case of recent history (<6 months) of cardiovascular or thromboembolic disease and non-controlled cardiovascular risk factors

  • History of Stevens-Johnson's syndrome or Lyell's syndrome

  • Cytopenia (PNN ≤ 1,0 Giga/L or platelets ≤ 50 Giga/L or hemoglobin ≤ 8.5 g/dL)

• Active SARS-CoV-2 infection (patient can be included once infection resolved)

• Any medical condition which limits the ability of participant to participate in study

• Necessity to use a drug incompatible with ruxolitinib (see 7.4)

• Hypersensitivity to the IMP's active substance (ruxolitinib) or to any of the excipients (Cellulose microcrystalline, magnesium stearate, silica colloidal anhydrous, sodium carboxymethyl starch (Type A), povidone K30, hydroxypropylcellulose 300 to 600 cps, lactose monohydrate)

• Non-affiliation to a social security scheme or to another social protection scheme, patient on state medical aid

• Foreseeable inability, according to the investigator, to participate in all the visits, treatments and measures provided for in the protocol

• Concomitant participation in another clinical trial on medical product for human use, to a clinical investigation on a medical device, to interventional study involving human participants or in the exclusion period at the end of a previous clinical trial on medical product for human use, a clinical investigation on a medical device, or study involving human participants.

Participation in non-interventional research is permitted.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Ruxolitinib	Randomization in experimental group.
Control group	Placebo	Randomization in control group.

Primary Outcome Measures

Name	Time	Method
6 minutes-walk distance (6MWT): A distance walked in 6 min. superior in treated patients compared to placebo group	12 months	The 6MWT is performed in a corridor, between two cones separated by a distance of 25 m.

Secondary Outcome Measures

Name	Time	Method
Adverse events (safety and tolerability) of ruxolitinib in IBM patients	Through study completion that is to say 15 months	Adverse events collected according to the MedDRA classification
Therapeutic muscular efficacy of ruxolitinib on muscle strength	Until last consultation that is to say 12 months	Quantification of muscle strength using dynamometer
Therapeutic muscular efficacy of ruxolitinib on overall muscle status	Until last consultation that is to say 12 months	Measurement of overall muscle status using scales and serum creatine kinase (CK) levels
Respiratory ability	12 months	Forced vital capacity (FVC) measurement
Evaluate swallowing using Swallowing Disturbance Questionnaire (SDQ)	12 months	Measurement of the swallowing disorders via Swallowing Disturbance Questionnaire (SDQ). 15 items. Overall score from 0,5 to 44,5. The score increase with the swallowing disorders.
Quantification of fat replacement of muscle tissue at MRI	12 months	Measurement of the differences in fat fraction value calculated on thigh Dixon MRI pictures
Evaluate quality of life using Health Assessment Questionnaire without Disability Index (HAQ-DI)	12 months	Measurement of the difference in the quality of life measured by Health Assessment Questionnaire without Disability Index (HAQ-DI). 8 dimensions rated from 0 (without any difficulty) to 3 (unable to do). Overall score from 0 to 3. The higher the score, the lower the quality of life.
Evaluate quality of life using Duke health profile	12 months	Measurement of the difference in the quality of life measured by Duke health profile - The Duke. 10 dimensions. Overall score from 0 to 100. The score increase with the quality of life.