Active Idiopathic Inflammatory Myopathy (IIM) MedDRA version: 24.1 Level: PT Classification code 10085970 Term: Idiopathic inflammatory myopathy System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
argenx BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Ability to consent in the jurisdiction in which the study is taking place and capable of giving signed informed consent. • A definite or probable clinical diagnosis of idiopathic inflammatory myopathy (IIM) • One of the following medical histories: a. Diagnosis of dermatomyositis (DM) or juvenile dermatomyositis (JDM), (age of disease onset 5 years from the screening date. b. Diagnosis of polymyositis (PM) (including antisynthetase syndrome (ASyS)) c. Diagnosis of immune-mediated necrotizing myopathy (IMNM) • Diagnosed with active disease as defined by the presence of at least 1 of the following criteria: a. Abnormal levels of at least 1 of the following enzymes: creatine kinase (CK), aldolase, lactate dehydrogenase, aspartate aminotransaminase (AST), alanine aminotransferase (ALT), based on central laboratory results b. Electromyography demonstrating active disease within the past 3 months c. Active dermatomyositis (DM) skin rash d. Muscle biopsy indicative of active idiopathic inflammatory myopathy (IIM) in the past 3 months e. Magnetic resonance imaging within the past 3 months indicative of active inflammation • Muscle weakness • Receiving a permitted background treatment for IIM. Permitted background treatment includes: oral corticosteroids; 1 antimalarial; or 1 of the following immunosuppressants: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, leflunomide, or mizoribine. Participants may receive a combination of either oral corticosteroids and up to 1 antimalarial or oral corticosteroid and up to 1 immunosuppressant. • Contraceptive use by nonsterilized male participants and women of childbearing potential will be consistent with local regulations, where available, for individuals participating in clinical studies. Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline to establish the nonpregnant state before receiving investigational medicinal product (IMP). The full list of inclusion criteria can be found in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 220 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • A clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening • A COVID-19 polymerase chain reaction (PCR)-positive test before enrollment • Any other known autoimmune disease that, in the investigator’s opinion, would interfere with an accurate assessment of clinical symptoms of IIM or put the patient at undue risk • A history of malignancy unless considered cured by adequate treatment, with no evidence of recurrence for = 3 years before the first administration of the IMP. Adequately treated participants with the following cancers can be included at any time: a. Basal cell or squamous cell skin cancer b. Carcinoma in situ of the cervix c. Carcinoma in situ of the breast d. Incidental histological finding of prostate cancer • Severe muscle damage • Glucocorticoid-induced myopathy that the investigator considers the primary cause of muscle weakness or permanent weakness linked to a non-IIM cause • JDM diagnosed > 5 years from screening or juvenile myositis with extensive calcinosis or severe calcinosis. • Uncontrolled interstitial lung disease or any other uncontrolled IIM manifestation that, in the opinion of the investigator, would be likely to require treatment with prohibited medication during the study • Other inflammatory and noninflammatory myopathies: inclusion body myositis, overlap myositis, metabolic myopathies, muscle dystrophies or a family history of muscle dystrophy, drug-induced or endocrine induced myositis, and juvenile myositis (other than JDM) • Clinically significant disease, recent major surgery or intends to have surgery during the study, or has any other condition in the opinion of the investigator that could confound the results of the study or put the patient at undue risk • Known hypersensitivity reaction to IMP or 1 of its excipients • Received a live or live-attenuated vaccine less than 4 weeks before screening. • Lack of clinical response to plasmapheresis/plasma exchange (PLEX) • Positive serum test at screening for active viral infection with any of the following conditions: a. Hepatitis B virus (HBV) b. Hepatitis C virus (HCV) c. HIV • Any of the following prior therapy or procedures: a. Treatment within 2 weeks before screening: topical corticosteroids or topical immunomodulators (eg, tacrolimus) for IIM rash b. Treatment within 4 weeks before screening: local corticosteroid injections, anakinra, etanercept, Janus kinase (JAK) inhibitors, corticosteroids, PLEX, immunoadsorption c. Treatment within 8 weeks before screening: corticosteroid precursors d. Treatment within 12 weeks before screening: IVIg, SCIg, tocilizumab, abatacept, infliximab, adalimumab, golimumab, certolizumab, ustekinumab e. Treatment within 24 weeks before screening: rituximab or other anti-CD20 antibody, cyclophosphamide f. Use of a nonbiologic investigational product within 12 weeks before screening g. Use of a biologic therapy and/or monoclonal antibody within 24 weeks before screening h. Treatment with oral corticosteroids i. Treatment with >1 immunosuppressant, >1 antimalarial, or a combination of an immunosuppressant and an antimalarial • Participant has previously participated in an efgartigimod clinical study and received at least 1 dose of IMP • Participant is concurrently participating in any other clinical study, including a noninterventional study • Participant has a current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse • Participa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the clinical improvement of efgartigimod PH20 SC treatment compared with placebo, in addition to standard-of-care immunomodulatory therapy;Secondary Objective: IMP = efgartigimod PH20 SC • Evaluate additional measures of efficacy of IMP in achieving clinical response • Evaluate effect of IMP on: - muscle strength - patient and physician global assessments of disease activity - physical function parameters • Evaluate steroid-sparing effect of IMP (phase 3 stage only) • Evaluate effect of IMP on: - extramuscular disease activity - additional measures of muscle strength - additional measures of patient and physician global assessments of disease activity - muscle endurance - pain - fatigue - additional physical functioning measures • Assess health impact of glucocorticoid use and evaluate steroid-sparing effect of IMP (phase 3 stage only) • Evaluate effect of IMP on: - health-related quality of life - muscle enzymes - preventing disease deterioration • Assess: - PK of IMP - PD effect on total IgG levels of IMP - immunogenicity of IMP and rHuPH20 - safety and tolerability of IMP;Primary end point(s): Total improvement score (TIS) ;Timepoint(s) of evaluation of this end point: Phase 2: up to 24 weeks; phase 3: up to 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints • Time to reach TIS =20 (first “minimal clinical improvement”) • Percentage of participants with TIS =20 • Time to reach TIS =40 (first “moderate clinical improvement”) • Percentage of participants with TIS =40 • Change in manual muscle testing-8 (MMT8) score • Change in Patient Global Assessment of Disease Activity (PGA) • Change in Physician Global Assessment of Disease Activity (MDGA) • Change in Health Assessment Questionnaire Disability Index (HAQ-DI) • Change in steroid dose from baseline to last visit • Proportion of participants achieving target dose of =5 mg (prednisone equivalent) • Change in the Extramuscular Global Assessment Other Secondary Endpoints • Change in abbreviated handheld dynamometry • Change in Patient Global Impression of Severity (PGI-S) • Patient Global Impression of Change (PGI-C) • Change in Clinical Global Impression of Severity (CGI-S) • Clinical Global Impression of Change (CGI-C) • Change in the Myositis Functional Index (FI-3) • Change in Patient Reported Outcomes Information System (PROMIS) Pain Interference 6a v1.0 • Change in pain numeric rating scale (NRS) assessing worst pain in the past 7 days • Change in PROMIS Fatigue 7a v1.0 • Change in Fatigue NRS assessing worst physical fatigue in the past 7 days • Change in PROMIS Physical Function 8b v2.0 • Change in the Physical Functioning subscale and Physical Component Summary scores of the 36-Item Short Form Survey version 2 (SF-36v2) • Composite Glucocorticoid Toxicity Index (C-GTI) comprising the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS) • Change in EQ-5D-5L utilities • Change in EQ-5D-5L VAS • Change in the most abnormal enzyme, in each participant: creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransaminase (AST), and aldolase, or lactate dehydrogenase (LDH) • Proportion of participants who meet protocol-defined worsening criteria • Time to worsening • Efgartigimod seru | — |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Czech Republic, Denmark, France, Georgia, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, Peru, Poland, Portugal, Serbia, Slovakia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactRegulatory
argenx BV
Outcome results
None listed