Blocage de l'interféron-ɣ par le ruxolitinib pour le traitement de la myosite à inclusion : un essai de phase IIb

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]

Trial duration

27 May 2025 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Programme Hospitalier de Recherche Clinique - PHRC (French Ministry of Health)

External identifiers

EU CT number

2023-507666-32-00

ClinicalTrials.gov

NCT06536166

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

to evaluate whether ruxolitinib may improve the overall locomotor performance of IBM patients after a 1 year duration treatment period

Secondary objectives 4

1. To evaluate the safety and tolerance of ruxolitinib in IBM patients.
2. 2. To evaluate the therapeutic efficacy of ruxolitinib on various parameters depending on skeletal muscle involvement: (i) The muscle strength: maximal voluntary isometric muscle strength for hand grip (finger flexors), knee extension and flexion and elbow flexion and extension (ii) The overall muscular status: ability to walk, overall motor function, myonecrosis (iii) The respiratory ability: forced vital capacity (FVC) (iv) The swallowing (v) ) The proportion of adipose component in muscle tissues, residual muscle tissue and markers of disease activity using at magnetic resonance imaging (MRI)
3. 3. To evaluate the impact of ruxolitinib treatment on the quality of life: Health Assessment Questionnaire without Disability Index (HAQ-DI), Duke health profile.
4. 4. To assess the quality of the blinding in this trial

Conditions and MedDRA coding

Inclusion body Myositis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. - Age ≥ 45 years
2. - Effective contraception for the duration of the clinical trial for fertile women of childbearing age. The participant agrees to follow the contraceptive requirements detailed in the protocol.
3. - 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
4. - To be able to walk 6 min without assistance from another person (external assist devices permitted [e.g., canes, walkers, or rollators])
5. - Patient informed and having signed the consent for participation, possibly assisted by a trusted person

Exclusion criteria 15

1. - Pregnancy or breastfeeding
2. - Patient under guardianship, curatorship, safeguard of justice or deprived of liberty
3. - Patient with cognitive disorders or unable, according to the investigator, to understand the study and/or to give informed consent According to the appreciation of the investigator, non-French speaking patients may be included if a close one is able to translate the information provided. The patient must be able to benefit from the accompaniment of a relative for all of their visits (in teleconsultation and in hospital).
4. - Quadriceps weakness (manual muscle testing, MRC) below or equal 1
5. - Forced vital capacity (FVC) or forced expiratory volume (FEV) < 50% of predicted value
6. - Concomitant use of immunomodulatory drugs including previous treatment with JAK inhibitor, or medications acting on muscle anabolism or catabolism
7. - Live vaccine within the 4 weeks before starting ruxolitinib therapy
8. - Comorbidity or active chronic disease which contraindicate ruxolitinib: • If the results of the biological assessment including blood count, blood formula and biochemistry and dating back less than three months are available, see the non-inclusion criteria below. For patients whose results of the biological assessment carried out on the day of the inclusion and randomization visit are not yet available, these criteria constitute secondary exclusion criteria to be checked upon receipt of the results and before the randomization.  Lipid parameters abnormalities/elevations (in lack of cardiovascular risk factors, normal values with or without lipid-lowering treatment are: CTtotal cholesterol < 2 g/L; LDL-C < 1.6 g/L; HDL-C > 0.4 g/L; TGtriglycerides < 1.5 g/L)  Severe renal impairment (stage 4) and end-stage renal disease (stage 5): GFR < 30mL/min/1.73m2  Hepatic impairment: AST/ALT > 3 ULN and bilirubin > 1.5 ULN  Cytopenia (polymorphonuclear neutrophilsPNN ≤ 1.5 Giga/L or platelets ≤ 75 Giga/L or hemoglobin ≤ 10 g/dL)
9. - Active SARS-CoV-2 infection (patient can be included once infection resolved)
10. - Any medical condition which limits the ability of participant to participate in study
11. - Necessity to use a drug incompatible with ruxolitinib (see 7.4)
12. - 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)
13. - Non-affiliation to a social security scheme or to another social protection scheme, patient on AME (state medical aid)
14. - Foreseeable inability, according to the investigator, to participate in all the visits, treatments and measures provided for in the protocol
15. - 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement of 60 meters for the distance walked during 6-minute (6WMD) from baseline to M12 (6MWD).

Secondary endpoints 4

1. 1. Safety and tolerance of ruxolitinib in IBM patients: Adverse events according to the MedDRA classification.
2. Therapeutic muscular efficacy of ruxolitinib through change from baseline to M12 of the parameters depending on skeletal muscle involvement: (i) Muscle strengt (ii) Overall muscle status, (iii) Respiratory ability, (iv) Swallowing, (v) Lower limb Quantification of fat replacement of muscle tissue, residual muscle tissue and markers of disease activity using MRI
3. 3. Improvement or stability between baseline and M12 in quality of life assessed by the scoring through Health Assessment Questionnaire without Disability Index (HAQ-DI), Duke health profile.
4. 4. Quality of the blinding assessed by the New Blinding Index (Bang, 2004).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr François Jérôme AUTHIER

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Malika Yahmi

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications