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A Phase IIa Trial of the Oral JAK 1/2 Inhibitor, Baricitinib, in the Treatment of Adult IIM (MYOJAK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04208464
Recruitment Status : Not yet recruiting
First Posted : December 23, 2019
Last Update Posted : December 23, 2019
Sponsor:
Collaborators:
Eli Lilly and Company
Manchester Clinical Trials Unit
Karolinska Institutet
Information provided by (Responsible Party):
Hector Chinoy, University of Manchester

Tracking Information
First Submitted Date  ICMJE December 19, 2019
First Posted Date  ICMJE December 23, 2019
Last Update Posted Date December 23, 2019
Estimated Study Start Date  ICMJE July 1, 2020
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2019)
Assess the clinical response at 24 weeks post-active treatment [ Time Frame: Arm A: 24 weeks post randomisation; Arm B: 36 weeks post randomisation ]
Minimal, moderate or major clinical response according to the IMACS criteria at 24-weeks post active treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2019)
  • Compare the clinical response between arm A and arm B at 12 and 24 weeks post randomisation [ Time Frame: 12 weeks and 24 weeks post randomisarion ]
    Minimal, moderate or major clinical response according to the IMACS criteria
  • Compare the clinical response between arm A and arm B at 24-weeks post active treatment [ Time Frame: Arm A: 24 weeks post randomisation; Arm B: 36 weeks post randomisation ]
    (b) Moderate or major clinical response according to the IMACS criteria at 24 weeks post active treatment
  • Assess the time taken to achieve clinical improvement following treatment with baricitinib up to 24 weeks after active treatment [ Time Frame: Arm A: 24 weeks post randomisation; Arm B: 36 weeks post randomisation ]
    Time taken to achieve minimal, moderate or major clinical response in myositis up to 24 weeks after active treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase IIa Trial of the Oral JAK 1/2 Inhibitor, Baricitinib, in the Treatment of Adult IIM
Official Title  ICMJE A Randomised, Phase IIa Treatment Delayed-start Trial of the Oral JAK 1/2 Inhibitor, Baricitinib, in the Treatment of Adult Idiopathic Inflammatory Myopathy
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 barcitinib treatment after an initial 12-week delay with a 4 week follow up period for safety.
Detailed Description

Potential participants will attend a screening visit to confirm their eligibility to participate in the trial. Once eligibility is confirmed the participant will be randomised to receive 24 weeks of baracitinib from the baseline visit with 12 weeks of follow up or receive 24 weeks of baracitinib after a delayed-start of 12 weeks from the baseline visit.

Participants will attend study visits every 4 weeks starting at the baseline visit at week 0. At each visit data will be collected about the following:

  1. Muscle function
  2. Signs of disease activity
  3. Vital signs
  4. Physical examination
  5. A blood test to check blood count, liver and kidney function and markers of inflammation for safety purposes.
  6. Participant reported assessment of how disease disease is progressing and how it affects their day-to-day life.

In addition the following data will be collected at week 0, week 12, week 24 and week 36:

  1. Signs of disease damage
  2. Blood and urine sample collection for biomarker analysis
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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.
Masking: Single (Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Inflammatory Myopathies
Intervention  ICMJE
  • Drug: Baricitinib
    4mg daily for 24 weeks from baseline
  • Drug: Baricitinib
    4mg daily for 24 weeks starting after a 12-week treatment delay from baseline
Study Arms  ICMJE
  • Experimental: Arm A
    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.
    Intervention: Drug: Baricitinib
  • Experimental: Arm B
    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.
    Intervention: Drug: Baricitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 19, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2022
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Participant meets EULAR/ACR classification criteria for IIM (at least 55% probability).
  2. 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.
  3. Inflammatory active disease based on persisting or worsening muscle weakness; MMT < 150 or low endurance (FI -3 < 20% of upper value), together with at least one other sign of active disease: elevated serum levels of at least one muscle enzyme (CK, LDH, AST, ALT) above upper limit of normal and being explained by muscle involvement and no other cause e.g. liver disease, inflammation in recent muscle biopsy or on MRI scans (<12 weeks), or active extra muscular disease: dermatomyositis-specific skin rash, arthritis or interstitial lung disease (ILD) (as suggested by chest x-ray/ high resolution computerised tomography (HRCT) or pulmonary function test (reduction of TLCO by 15% and/or FVC by 10% from baseline)) and on the treating physicians' judgement.
  4. 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).
  5. For polymyositis, a muscle biopsy is required to confirm the diagnosis (performed at any time before the start of the study) and to exclude other conditions unless a participant is positive for myositis specific (anti-synthetase, NXP2, SAE1, TIF1g, Mi2, MDA5, SRP, HMGCR) or myositis-associated autoantibodies (Ro52, Ro60, PmScl, RNP). Polymyositis will be included after a judicial process by the three PIs.
  6. Are receiving at least one of the following standard of care medications within the required timeframe:

    • A single antimalarial (e.g. hydroxychloroquine) at a stable therapeutic dose for at least 8 weeks prior to the screening visit

    • A single immunosuppressant (such as methotrexate (MTX), azathioprine, mycophenolate) 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)
    • If the subject is taking combination immunosuppressive therapy, then this should be reduced to one drug at a stable dose for 4 weeks before baseline.
    • Ciclosporine, tacrolimus or cyclophosphamide should be stopped at least 4 weeks before the first administration of baricitinib.
  7. Age ≥18 years.
  8. Full capability of providing informed consent.

Exclusion Criteria:

  • 1. Participants with other types of inflammatory myopathies including:

    • Drug induced myositis
    • Inclusion body myositis
    • Malignancy-associated myositis
    • Immune-mediated necrotizing myopathy

      2. Participants unable to participate in clinical assessments or provide biological specimens as per the study protocol 3. Participants where the use of bariticinib would be contraindicated 4. Participants with known allergies to IMP or excipients 5. Women with a positive pregnancy test on enrolment or prior to start of study drug administration 6. Women who are known to be pregnant or breastfeeding 7. 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).

      8. 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.

      9. Concomitant medical conditions that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study.

      10. Participants with a history of venous thromboembolism including deep vein thrombosis and pulmonary embolism.

      11. 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.

      12. 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.

      13. Participants with any serious bacterial infection (such as pneumonia, other renal infection and sinusitis), unless treated and resolved with antibiotics.

      14. Participants with any chronic bacterial infection (such as pyelonephritis and chest infection with bronchiectasis) in the previous 12 weeks before screening.

      15. Participants with active tuberculosis (TB) requiring treatment within the previous 3 years. Subjects with a positive PPD and/or Quantiferon assay at screening will not be eligible for the study unless they have completed at least 4 weeks of treatment for latent TB, have a negative chest x-ray at enrolment, and commit to completing the course during the study. Such cases should be discussed with a respiratory physician as per local guidelines. A PPD response that is equal to or greater than 10 mm should be considered a positive test, although more conservative criteria may be applied as determined by the clinical circumstance and investigator according to published guidelines and/or local standards endorsed by the medical society. PPD and/or Quantiferon positive participants who have previously completed treatment for latent tuberculosis according to the local guidelines may be considered for enrolment. Equivocal Quantiferon results will need to be discussed with a local respiratory physician.

      16. Participants with herpes zoster that resolved less than 8 weeks prior to the screening visit.

      17. Participants with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the screening visit, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection, positive HepBsAg, HepBcAb or hepatitis C antibody.

      18. Significant toxicities associated with concomitant or previous immunosuppressive/biologic therapy that would preclude subjects from participating and completing the study.

      19. Participants with clinically apparent immunodeficiency syndrome, (IgA deficiency alone is not an exclusion criterion).

      20. Participants with any of the following laboratory values at screening:

    • Haemoglobin (Hb) < 80 g/litre
    • Absolute lymphocyte count (ALC) < 500 cells/mm3
    • Absolute neutrophil count (ANC) < 1000 cells/mm3
    • Platelets <100,000/mm3 (100 x 109/L)
    • Creatinine clearance <30ml/min. Note: participants with creatinine clearance between 30-60mL/min should receive a reduced oral dose of 2mg baricitinib OD.
    • Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.

      21. For participants previously treated with rituximab: B cell levels less than lower limit of normal as measured by Fluorescent Activated Cell Sorting (FACS) analysis.

      22. For all participants who have received prior rituximab, a normal CD19 B cell count must be documented at the time of screening for this study.

      23. Participants who have received treatment with any investigational drug within 28 days of the first dose of IMP.

      24. Participants who have at any time received treatment with JAK/STAT inhibitors.

      25. Administration of live/ attenuated vaccines in the 4 weeks prior to screening and during the study. Effect on vaccine efficacy or the risk of infection transmission is unknown. In addition, clinical safety has not been established.

      26. Concomitant use of targeted biologic therapies at any time during the study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Holly Woodwark +44 (0) 161 306 3163 myojak@manchester.ac.uk
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04208464
Other Study ID Numbers  ICMJE R123899
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: As part of the consent process participants will consent to their anonymised data being shared with other researchers.
Responsible Party Hector Chinoy, University of Manchester
Study Sponsor  ICMJE University of Manchester
Collaborators  ICMJE
  • Eli Lilly and Company
  • Manchester Clinical Trials Unit
  • Karolinska Institutet
Investigators  ICMJE
Principal Investigator: Hector Chinoy University of Manchester
PRS Account University of Manchester
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP