JAK 1/2 Inhibitor, Baricitinib, in the Treatment of Adult IIM

NCT04208464 | Completed Phase 2 DMC

• 1 other identifier: R123899
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the clinical efficacy of baricitinib in patients with adult idiopathic inflammatory myositis (IIM). Half of the patients enrolled onto the study will receive 24 weeks of baricitinib from the baseline visit with a 12 week follow-up period. The other half of patients will receive 24 weeks of barcitinib treatment after an initial 12-week delay with a 4 week follow up period for safety.

Conditions

Idiopathic Inflammatory Myopathies

Outcome Measures

Primary Outcomes (1)

• Assess the clinical response across treatment arms after 24 weeks of active treatment.

  Response (yes/no): where 'response' is defined as 'achieving at least minimal clinical response according to the IMACS criteria at 24 weeks post-active treatment (at 24 weeks in the immediate-start arm and at 36 weeks in the delayed-start arm)'.

  Immediate-start arm: 24 weeks after baseline visit; Delayed-start arm: 36 weeks after baseline visit

Secondary Outcomes (7)

• To assess the extent of clinical response across treatment arms after 24 weeks of active treatment

  Immediate-start arm: 24 weeks after baseline visit; Delayed-start arm: 36 weeks after baseline visit

• To compare the clinical response between treatment arms: (i) at 12 weeks and (ii) at 24 weeks

  For both arms: 12 weeks and 24 weeks after the baseline visit

• To compare the clinical response between treatment arms after 24 weeks of active treatment.

  Immediate-start arm: 24 weeks after baseline visit; Delayed-start arm: 36 weeks after baseline visit

• To assess the time taken to achieve clinical response across treatment arms up to 24 weeks of active treatment.

  Immediate-start arm: 24 weeks after baseline visit; Delayed-start arm: 36 weeks after baseline visit

• To compare the change from baseline between treatment arms in the following outcomes: - Individual components of the IMACS CSMs - Physical functioning - Muscle endurance - Pain - Fatigue - Health-related quality of life

  Immediate-start arm: 12 weeks and 24 weeks after baseline visit; Delayed-start arm: 12 weeks, 24 weeks and 36 weeks after baseline visit

Study Arms (2)

Immediate-start arm

EXPERIMENTAL

Participants will receive 4mg baracitinib daily for 24 weeks from the baseline visit in week 0. After treatment participants will be followed up for 12 weeks.

Drug: Baricitinib

Delayed-start arm

EXPERIMENTAL

After the baseline visit in week 0, participants will wait for a 12 week treatment delay and will then receive 4mg baracitinib daily from week 12-week 36 (i.e. for 24 weeks). After treatment participants will be followed up for 4 weeks for safety.

Drug: Baricitinib

Interventions

Baricitinib DRUG

4mg daily for 24 weeks from baseline

Immediate-start arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant meets EULAR/ACR classification criteria for polymyositis (PM) or dermatomyositis (DM) (at least 55% probability).
• Persisting disease activity as defined in (3), after a minimum of 12 weeks treatment with prednisolone or equal drug. The history of treatment with prednisolone (or equal) should include the dose of ≥ 20mg/day for at least 4 weeks. Prednisolone should be at a stable dose of ≤ 20 mg/day for at least 4 weeks prior to the baseline visit.
• If criteria in (2) not met, then to fulfil sum of Physician global assessment, participant global assessment and extra muscular global assessment visual analogue scale (VAS) score ≥ 10 cm (all scales individually on 0-10 cm scale).
• For polymyositis, a participant can be included if they are positive for myositis specific (anti-synthetase, NXP2, SAE1, TIF1g, Mi2, MDA5,) or myositis-associated autoantibodies (Ro52, Ro60, PmScl, RNP). Polymyositis will be included after a judicial process by the three PIs.
• Are receiving at least one of the following standard of care medications within the required timeframe:
• A single antimalarial (e.g. hydroxychloroquine) for 3 months and at a stable therapeutic dose for at least 8 weeks prior to the screening visit
• A single immunosuppressant (such as methotrexate (MTX), azathioprine, mycophenolate) for 3 months and at a stable therapeutic dose for at least 4 weeks prior to the screening visit
• An oral corticosteroid, at a stable dose ≤ 20 mg/day prednisone (or equivalent), for at least 4 weeks prior to baseline (visit 1)
• Age ≥18 years.
• Full capability of providing informed consent.

You may not qualify if:

• Participants with other types of inflammatory myopathies including:
• Drug induced myositis
• Malignancy-associated myositis
• Immune-mediated necrotizing myopathy
• Participants unable to participate in clinical assessments or provide biological specimens as per the study protocol
• Participants where the use of bariticinib would be contraindicated
• Participants with known allergies to IMP or excipients
• Women with a positive pregnancy test on enrolment or prior to start of study drug administration
• Women who are known to be pregnant or breastfeeding
• Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 1 week after treatment (Please see Appendix 3 for definitions and acceptable methods of contraception).
• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, pulmonary, cardiac, neurological, ophthalmologic or cerebral disease with the exception of those symptoms that are a manifestation of polymyositis or dermatomyositis.
• Concomitant medical conditions that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study.
• Participants with a history of venous thromboembolism including deep vein thrombosis and pulmonary embolism.
• Participants with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection), including carcinoma-in-situ. Existing non-melanoma skin cell cancers must be removed prior to IMP dosing. Participants with dermatomyositis need to be screened for malignancies according to routine procedures.
• Participants who have a history of clinically significant drug or alcohol abuse. Subjects currently taking MTX who admit to consumption of more than an average of 1 alcoholic drink per day.

Sponsors & Collaborators

• University of Manchester: lead
• Eli Lilly and Company: collaborator
• Clinical Trials Unit, Manchester: collaborator
• Karolinska Institutet: collaborator

Study Sites (1)

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Myositis

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Hector Chinoy

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The participant and investigators will not be blinded because it will be clear whether IMP is being administered from baseline or after a 12 week delayed start. However every attempt will be made to keep the muscle function and disease activity and damage outcome assessor blinded to the treatment arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Rheumatology and Neuromuscular Disease

Model Details: This is a randomised, treatment-delayed trial design. Participants will be randomised into two arms: participants in one arm will receive 24 weeks of baracitinib treatment from baseline with 12 weeks of follow up; participants in the other arm will have a delayed treatment start for 12 weeks, then will receive 24 weeks of baracitinib treatment with 4 weeks of follow up for safety.

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 23, 2019
• Study Start: October 7, 2021
• Primary Completion: September 25, 2023
• Study Completion: September 25, 2023
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)