An Exploratory Study on the Efficacy and Safety of Abatacept in the Treatment of Refractory Dermatomyositis

Dermatomyositis is a heterogeneous disease characterized by involvement of the proximal muscles of the extremities. Some patients have treatment failure or intolerance to the above treatment regimens, which is called refractory dermatomyositis. Abatacept has been approved by the FDA for the treatment of three types of rheumatoid immune diseases, and the international consensus of experts recommends abacepil as a second-line regimen for the treatment of refractory dermatomyositis based on the evidence of case reports.

Study Overview

• Status: Recruiting
• Conditions: Dermatomyositis; Abatacept
• Intervention / Treatment: Drug: Abatacept

Detailed Description

Dermatomyositis is a heterogeneous disease characterized by involvement of the proximal muscles of the extremities. Some patients have skin, lung and other systems involved. The clinical manifestations of dermatomyositis are varied and vary from person to person, so the treatment should follow the principle of individualization. At present, glucocorticoid combined with immunosuppressants (including methotrexate, azathioprine, cyclosporine, tacrolimus, mycophoranate, cyclophosphamide, etc.) is the first choice for the treatment of dermatomyositis. Some patients have treatment failure or intolerance to the above treatment regimens, which is called refractory dermatomyositis. There has not been a large-scale study to explore the treatment regimens. Abatacept is a CTLA-4 fusion protein that inhibits T cell activation by competitively binding to CD80/CD86 and blocking the second signal. To date, Abatacept has been approved by the FDA for the treatment of three types of rheumatoid immune diseases (refractory rheumatoid arthritis, juvenile idiopathic arthritis, and active psoriatic arthritis). The international consensus of experts recommends abacepil as a second-line regimen for the treatment of refractory dermatomyositis based on the evidence of case reports. However, to date, there is no relevant report or clinical study registration information of Abatacept in the treatment of dermatomyositis. The purpose of this study was to prospectively observe the efficacy and safety of Abatacept in the treatment of refractory dermatomyositis through a controlled before and after study.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Wenfeng Tan, PhD, MD; Phone Number: 086 18061202878; Email: tanwenfeng@jsph.org.cn
      • Contact: Lingxiao Xu, PhD, MD; Phone Number: 086 18020130778; Email: lingxiao32@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Dermatomyositis confirmed in accordance with Bohan-Peter criteria for inflammatory myopathy, or clinically free myopathic dermatomyositis according to the revised Sontheimer criteria, aged 18 years or older, regardless of gender.
2. Patients with refractory dermatomyositis, specifically defined as those who have received glucocorticoid combined with at least one immunosuppressive therapy for at least 3 months and have failed treatment or intolerance to treatment.Treatment failure was defined as improvement of 3 core parameters in the core assessment measures of iMACS <20%, or more than 2 parameters deterioration >25%.Treatment intolerance is defined as a patient experiencing side effects that require discontinuation of the drug or an underlying condition that prevents further use of the drug.Before enrollment, the dosage of glucocorticoids was <1mg/kg/day, prior use of at least one immunosuppressant (including methotrexate, azathioprine, cyclosporine, tacrolimus, mycophenolic ester and cyclophosphamide, etc.) at a stable dose >3 months.
3. If the patient has previously used biological agents, etc., the washout period shall be completed.
4. Patients or their guardians fully understand the content of this study, are willing to participate in the study, and sign the informed consent.

Exclusion Criteria:

1. Other rheumatoid immune diseases: including but not limited to rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, primary biliary cirrhosis, etc.
2. combined with other myopathy causing myopathy and myasthenia;These include neurological diseases (such as muscular dystrophy, myasthia gravis, amyotrophic lateral sclerosis, Guillain-Barre syndrome, etc.), tumors, drug effects (such as statins, etc.), infections, genetic diseases, endocrine diseases, electrolyte disorders, rhabdomyolysis, etc.
3. Patients with severe heart, liver, kidney and other important organs and blood and endocrine system lesions:Including but not limited to decompensated cardiac insufficiency, refractory hypertension and abnormal ecg, cereal third transaminase or aspertate aminotransferase more than 2 times higher than normal reference value online, renal tubular acidosis, renal interstitial lesions, renal insufficiency, serious leucopenia, severe anemia, severe thrombocytopenia and other serious diseases, such as tumor, etc.).
4. Active infection, glucocorticoid and immunosuppressive therapy may aggravate infection;Hepatitis B virus surface antigen and hepatitis C antibody were positive.Active TB patients who have been treated for active TB within the previous 3 years, or who have been screened for latent TB, and who are positive for PPD combined with T-SPOT, or positive for sputum bacteria.
5. Pregnant and lactating women, women of reproductive age who cannot guarantee contraception.
6. Patients with allergic constitution, who have been allergic to various drugs in the past.
7. Mental disorders, or other patients unable to cooperate with treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Refractory Dermatomyositis; Patients who have been receiving glucocorticoids in combination with at least one immunosuppressive therapy for at least 3 months and who have failed therapy or are intolerant to therapy

Drug: Abatacept; Abatacept is a CTLA-4 fusion protein that inhibits T cell activation by competitively binding to CD80/CD86 and blocking the second signal. To date, Abatacept has been approved by the FDA for the treatment of three types of rheumatoid immune diseases (refractory rheumatoid arthritis, juvenile idiopathic arthritis, and active psoriatic arthritis). The international consensus of experts recommends abacepil as a second-line regimen for the treatment of refractory dermatomyositis based on the evidence of case reports. However, to date, there is no relevant report or clinical study registration information of Abatacept in the treatment of dermatomyositis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IMACS score improved	Improvement of 3 core parameters of disease activity in the core assessment index of IMACS over 20 percent with no more than 2 parameters deteriorating over 25 percent. And parameters of IMACS include Physician Global Assessment, Patient Global Assessment, Muscle strength assessment with MMT-8, Sports Ability Assessment Questionnaire, laboratory evaluation including creatine kinase, aldolase, lactic dehydrogenase and so on, Evaluation of myositis disease activity using MDAAT and appraisal of life quality.	12 weeks after treat with Abatacept

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose of glucocorticoids used	Dose of glucocorticoids used	12 weeks after treat with Abatacept

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events	Occurrence of adverse events	12 weeks after treat with Abatacept

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: National Natural Science Foundation of China

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Anticipated): July 31, 2022
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: June 29, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Abatacept; Refractory Dermatomyositis
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Polymyositis; Myositis; Dermatomyositis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: ABA-DM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No