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

• ClinicalTrials.gov Identifier: NCT04946669
• Recruitment Status: Recruiting
• First Posted: July 1, 2021
• Last Update Posted: July 1, 2021
• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborator: National Natural Science Foundation of China
• Information provided by (Responsible Party): Wenfeng Tan, The First Affiliated Hospital with Nanjing Medical University

Tracking Information

• First Submitted Date: May 17, 2021
• First Posted Date: July 1, 2021
• Last Update Posted Date: July 1, 2021
• Actual Study Start Date: February 1, 2021
• Estimated Primary Completion Date: July 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2021)

IMACS score improved [ Time Frame: 12 weeks after treat with Abatacept ]

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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 29, 2021)

Dose of glucocorticoids used [ Time Frame: 12 weeks after treat with Abatacept ]

Dose of glucocorticoids used

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 29, 2021)

Occurrence of adverse events [ Time Frame: 12 weeks after treat with Abatacept ]

Occurrence of adverse events

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: An Exploratory Study on the Efficacy and Safety of Abatacept in the Treatment of Refractory Dermatomyositis
• Official Title: An Exploratory Study on the Efficacy and Safety of Abatacept in the Treatment of Refractory Dermatomyositis
• Brief Summary: 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.
• 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
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Dermatomyositis
• Abatacept

Intervention

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.

Study Arms

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

Intervention: Drug: Abatacept

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 29, 2021): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2022
• Estimated Primary Completion Date: July 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04946669
• Other Study ID Numbers: ABA-DM
• Has Data Monitoring Committee: No

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

• Plan to Share IPD: No

• Current Responsible Party: Wenfeng Tan, The First Affiliated Hospital with Nanjing Medical University
• Original Responsible Party: Same as current
• Current Study Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Original Study Sponsor: Same as current
• Collaborators: National Natural Science Foundation of China
• Investigators: Not Provided
• PRS Account: The First Affiliated Hospital with Nanjing Medical University
• Verification Date: June 2021