Ruxolitinib Treatment in Inclusion Body Myositis (BIGTIM)

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 2

Conditions: Inclusion Body Myositis, Sporadic

Treatments: Drug: Placebo; Drug: Ruxolitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06536166

APHP220829

Details and patient eligibility

About

Refer to the "Detailed Description" section.

Full 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 features. It differs from other IIMs by its chronic evolution and refractoriness to common immunomodulatory drugs leading to marked disability and poor quality of life. Histological and molecular analyses of muscle biopsies from IBM patients showed intense muscular type II interferon (IFNγ) signature, stronger than observed in other IIMs. In vitro and in vivo experimental studies showed that IFNγ exerts myosuppressive effects through JAK/STAT pathway activation mimicking the degenerative features observed in IBM, and that these effects can be prevented by JAK-inhibitor ruxolitinib.

Hypothesis/Objective : Ruxolitinib could be an effective therapy for IBM. Objective is to evaluate its therapeutic effects in IBM.

Method : Comparative, multicenter, randomized, parallel-group, superiority, placebo-controlled, double-blind, phase 2 trial. 60 IBM patients able to walk during at least 6mn will be randomized in two groups (30/group) and received either ruxolitinib 15mgx2/d or placebo during 1 yr. Evaluation includes 6MWT, muscle strength quantification, functional scales, respiratory functional test and muscle MRI.

Enrollment: 80 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Experimental group

Experimental group

Description:

Randomization in experimental group.

Treatment:

Drug: Ruxolitinib

Control group

Placebo Comparator group

Description:

Randomization in control group.

Treatment:

Drug: Placebo