dermatomyositis muscle disease
Conditions
Interventions
Subjects will be randomized 1:1 to 1 of 2 treatment sequences:
Sequence A: 0.5 g/kg IgPro20 for 24 weeks (study period 1) followed by 0.5
g/kgIgPro20 for 28 weeks (study period 2)
OR
Sequence B: pla
Sponsors
CSL Behring LLC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Capable of providing written informed consent by signing an informed consent form and willing and able to adhere to all protocol requirements • Age >= 18 years • Diagnosis of at least probable idiopathic inflammatory myopathies per European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria: minimum aggregate score of 5.5 without and 6.7 with muscle biopsy (historical muscle biopsy is acceptable) which includes confirmation of DM rash / skin manifestation (present or by history [historical skin biopsy is required for amyopathic DM subjects]) • Disease activity defined by: • Presence of DM rash / skin manifestation (eg, Gottron's papules / sign, heliotrope rash, periorbital edema, V sign, Shawl sign) at Screening Visit OR • One objective disease activity measure within 3 months before Baseline: o Magnetic resonance imaging showing active inflammation (edema) of a proximal skeletal muscle - OR - o Electromyogram showing acute changes such as spontaneous activity not explained by other disease - OR - o Muscle biopsy with perivascular or perimysial inflammation - OR - o CK > 4 x upper limit of normal (ULN) • Disease severity defined by a minimum value of 2 cm on a 10 cm Physician Global Disease Activity Visual Analog Scale and: o MMT-8 = 14 • Subject has failed other DM treatment or is on DM treatment such as immunosuppressants and/or antimalarials on a stable dose >= 3 months before Baseline; and/or oral corticosteroids (= 1 month before Baseline
Exclusion criteria
Exclusion criteria: • Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer • Evidence of malignancies diagnosed within the previous 5 years. Note: Subjects with a history of carcinoma in situ of the cervix that has been excised and cured with >= 5 years since excision or subjects with documented history of treated basal or squamous cell skin cancer may be enrolled into the study.. • Physician Global Damage Assessment >= 3 on a 5-point Likert scale where a score of 3 represents severe damage • Clinically relevant improvement between Screening Visit and Baseline, defined by >= 2 cm improvement on a 10 cm Physician Global Disease Activity Assessment Visual Analog Scale • Known or suspected hypersensitivity or other severe reactions to IgPro20 or to any of its excipients, or other immunoglobulins (Igs)or severe reactions to blood products • Other significant medical conditions that could increase the risk to the subject, eg: o History of allogeneic bone marrow / stem cell transplant / solid organ transplant o Cardiac insufficiency (New York Heart Association Class III or IV) or unstable ischemic heart disease o Chronic kidney disease stage IV or V o Recent surgery requiring general anesthesia within the previous 4 weeks before Screening o Known hyperprolinemia type I or type II o Documented thrombophilic abnormalities including blood hyperviscosity, protein C or protein S deficiency, anti-thrombin-III deficiency, plasminogen deficiency, antiphospholipid antibodies, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation o History of documented thrombotic episode, eg, pulmonary embolism, deep vein thrombosis, myocardial infarction, or thromboembolic stroke at any time o More than 3 of the following specified risk factors for thromboembolic events (documented and current conditions) occurring concurrently: atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (body mass index >= 30 kg/m2), recent significant trauma and immobility (wheelchairbound or bedridden) o Uncontrolled, severe, or rapidly progressive interstitial lung disease which will prevent the subject from successful participation in the study o Severe skin disease at planned infusion sites that would make subcutaneous (SC) infusions infeasible o Medical conditions whose symptoms and effects could alter protein catabolism and or Immunoglobulin G (IgG) utilization (eg, protein-losing enteropathies, nephrotic syndrome, known Immunoglobulin A [IgA] deficiency with antibodies to Immunoglobulin A) • Other conditions which would prevent correct assessment or lead to impaired muscle strength (eg, other neurological disorders including, but not limited to, Parkinson*s disease or severe musculoskeletal conditions like severe osteoarthritis or deformities) • Laboratory exclusions at Screening: o positive result for any of the following human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) o Creatinine > 1.5 × ULN or Blood Urea Nitrogen (BUN) > 3 × ULN • Any of the following therapies: o Within 1 month before Baseline: intramuscular, intravenous, or intra-articular corticosteroids including adrenocorticotropic hormone (any dose), doses > 20 mg/day prednisolone equiv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the responder status based on the total Improvement Score (TIS) assessments at Weeks 17, 21, and 25. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoints of the study are: * TIS at Week 25 * Change from Baseline in Manual Muscle Testing (MMT-8) at Week 25 * Change from Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score at Week 25 * Reduction of oral corticosteroid dose at Week 25 | — |
Countries
Netherlands
Outcome results
None listed