Study of Tofacitinib in Refractory Dermatomyositis

NCT03002649 | Completed Phase 1

• 1 other identifier: IRB00084227
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to obtain preliminary data regarding the safety and efficacy of Janus kinase (JAK) inhibitor, tofacitinib, in adults with active, treatment-refractory dermatomyositis.

Conditions

Dermatomyositis

Keywords

Dermatomyositis; Tofacitinib; Refractory dermatomyositis

Outcome Measures

Primary Outcomes (1)

• Number of participants who achieve International Myositis Assessment and Clinical Studies (IMACS) Definition of Improvement (DOI)

  IMACS DOI is 3 of any of the 6 core set measures (CSM) improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (worsening measure cannot include the manual muscle testing)

  Up to 12 weeks

Secondary Outcomes (3)

• Change from baseline in CDASI activity score

  Up to 16 weeks

• Safety and tolerability of tofacitinib as assessed by frequency of adverse events reported and observed

  Up to 16 weeks

• Safety and tolerability of tofacitinib as assessed by incidence of adverse events reported and observed

  Up to 16 weeks

Study Arms (1)

Tofacitinib

EXPERIMENTAL

All subjects will be provided Tofacitinib 11mg tablets for oral administration once daily. 12-week treatment period with optional 4-week treatment extension period.

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

Tofacitinib comes as an extended-release (XR) (long-acting) tablet to take by mouth. The extended-release tablet is usually taken with or without food once daily.

Also known as: Xeljanz XR, Tofacitinib citrate

Tofacitinib

Eligibility Criteria

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

You may qualify if:

• Study subjects must meet the following criteria:
• Definite or probable dermatomyositis by Bohan and Peter Criteria at least 6 months before screening
• Active skin disease as defined by a CDASI score of at least 5
• Skin biopsy proven disease
• Although not mandatory, patients with muscle weakness are eligible for enrollment. Those with active muscle disease must have a Manual Muscle Testing (MMT-8) score \< 142 out of 150
• Age \> 18
• Refractory myositis is defined by active disease despite a 12 week trial of steroids and with failure of response to at least prednisone and 1 other first line immunosuppressive agents (e.g. methotrexate, mycophenolate mofetil, or azathioprine) OR have demonstrated significant toxicity or intolerance to such therapies
• Maximum prednisone dose allowed will be 20mg/daily at time of entry to study provided that the dose has been stable for at least 2 weeks prior to baseline. Patients should not have received a daily therapy of more than 80mg of prednisone equivalent within 8 weeks prior to study entry
• Negative cancer screening conducted in the 6 months prior to screening visit
• Washout of immunosuppressive agents will be as follows:
• Azathioprine, mycophenolate, tacrolimus: 12-16 weeks prior to first dose of study drug;
• Rituximab: 12 months;
• Intravenous Immunoglobulin (IVIg): 3 months;
• Cyclophosphamide: 1 year;
• Methotrexate: 12-16 weeks.

You may not qualify if:

• The presence of any of the following excludes subject participation in the study:
• Use of other investigational drugs at the time of enrollment
• History of hypersensitivity to any of the study drugs or drugs of similar chemical classes
• DM patients having overlap myositis attributable to other causes such as scleroderma, arthritis, statin myopathy, steroid induced myopathy and/or significant organ damage e.g. lupus nephritis, central nervous system are present
• Late stage DM whose muscle weakness, according to the Investigator, could be attributable to muscle damage rather than myositis disease activity
• Patients with advanced clinically symptomatic interstitial lung disease
• Pregnancy or breast-feeding patients
• History of bowel rupture or inflammatory bowel diseases
• History of tuberculosis or mycobacterial infections
• Recent infection in the past 4 weeks before entry of study
• History of any malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
• Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection
• Diverticulitis or ulcers in stomach or intestines
• Evidence of any other acute or chronic infectious diseases
• Have received any live or live attenuated vaccines (including varicella or measles) within 2 months prior to study enrollment

Sponsors & Collaborators

• Johns Hopkins University: lead
• Pfizer: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Paik JJ, Casciola-Rosen L, Shin JY, Albayda J, Tiniakou E, Leung DG, Gutierrez-Alamillo L, Perin J, Florea L, Antonescu C, Leung SG, Purwin G, Koenig A, Christopher-Stine L. Study of Tofacitinib in Refractory Dermatomyositis: An Open-Label Pilot Study of Ten Patients. Arthritis Rheumatol. 2021 May;73(5):858-865. doi: 10.1002/art.41602. Epub 2021 Mar 24.

  PMID: 33258553 DERIVED

MeSH Terms

Conditions

Dermatomyositis

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Julie Paik, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 26, 2016
• Study Start: January 1, 2017
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: November 6, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)