PROSPECTIVE, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE III STUDY EVALUATING EFFICACY AND SAFETY OF OCTAGAM 10% IN PATIENTS WITH DERMATOMYOSITIS
- Conditions
- DermatomyositisDM1000381610028302
- Registration Number
- NL-OMON46776
- Lead Sponsor
- Octapharma Pharmazeutika Produktionsges m.b.H.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1.Subjects with diagnosis of definite or probable DM according to the Bohan and Peter criteria.;2.Subjects under treatment with corticosteroids and/or maximally 2 immune-suppressants and being on stable therapy for at least 4 weeks (see Section 4.2.1) OR Subjects with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressive drug, and with steroid/immunosuppressive drugs washed out as per Section 4.2.1 (Table 2). ;3. Subjects with active disease, assessed and agreed upon by an independent adjudication committee. being on stable therapy for at least 4 weeks.;4. Manual Muscle Testing-8 (MMT-8) score <142, with at least 2 other abnormal Core Set Measures (CSM) (Visual Analogue Scale [VAS] of patient global activity *2 cm, physician*s global disease activity *2 cm, extra-muscular activity *2 cm; at least one muscle enzyme >1.5 times upper limit of normal, Health Assessment Questionnaire *0.25).;5. Males or females * 18 to < 80 years of age.;6. Voluntarily given, fully informed written consent obtained from subject before any study-related procedures are conducted.;7. Subject must be capable to understand and comply with the relevant aspects of the study protocol.
1. Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer (except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 1 or 5 years, respectively have passed since excision).;2. Evidence of active malignant disease or malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors) or breast cancer diagnosed within the previous 10 years.;3. Subjects with overlap myositis (except for overlap with Sjögren*s syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile dermatomyositis or drug-induced myopathy.;4. Subjects with immune-mediated necrotizing myopathy with absence of typical DM rash.;5. Subjects with generalized, severe musculoskeletal conditions other than DM that prevent a sufficient assessment of the subject by the physician.;6. Subjects who have received IgG treatment within the last 6 months before enrolment.;7. Subjects who received blood or plasma-derived products (other than IgG) or plasma exchange within the last 3 months before enrolment.;8. Subjects starting or planning to start a physical therapy*directed exercise regimen during the trial.;9. Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease.;10. Severe liver disease, with signs of ascites and hepatic encephalopathy.;11. Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2).;12. Known hepatitis B, hepatitis C or HIV infection.;13. Subjects with a history of deep vein thrombosis within the last year prior to study enrollment or pulmonary embolism ever.;14. Body mass index *40 kg/m2.;15. Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).;16. Known IgA deficiency with antibodies to IgA.;17. History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products or any component of Octagam 10%.;18. Known blood hyperviscosity, or other hypercoagulable states.;19. Subjects with a history of drug abuse within the past 5 years prior to study enrollment.;20. Subjects unable or unwilling to understand or comply with the study protocol.;21. Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrollment.;22.Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to apply an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence or vasectomized partner) up to four weeks after the last IMP infusion.;23.Subjects who are accommodated in an institution or care facility based on an official directive or court order.;24.Subjects who are in any way dependent on the Sponsor, Investigator or Study Site.;25.Subjects who received forbidden medication within the washout period as defined in Section 4.2.2 (Table 3).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoints:<br /><br>* Proportion of responders in the 2.0 g/kg Octagam 10% and placebo arms at Week<br /><br>16. A responder is defined as a subject with an increase from baseline (Week 0)<br /><br>of *20 points on the Total Improvement Score (TIS).<br /><br><br /><br>Safety Endpoints:<br /><br>Safety (throughout the entire First and Extension Period):<br /><br>* Occurrence of all adverse events with particular emphasis on thromboembolic<br /><br>events (TEEs) and hemolytic transfusion reactions (HTRs).<br /><br>* Vital signs (blood pressure, heart rate, body temperature and respiratory<br /><br>rate).<br /><br>* Physical examination (at Screening and every 12 weeks from Week 4 on).<br /><br>* Laboratory parameters (hematology, clinical chemistry).<br /><br>Safety (at Baseline and end of Extension Period):<br /><br>* Tests for viral safety.<br /><br>* Pregnancy test, if applicable.</p><br>
- Secondary Outcome Measures
Name Time Method <p>SecondaryEfficacy Endpoints:<br /><br>* Proportion of TIS responders by improvement category (minimal, moderate,<br /><br>major) at Week 16 and Week 40.<br /><br>* Mean change from baseline (Week 0) to end of First Period (Week 16) in the<br /><br>modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI).<br /><br>* Mean change from end of First Period (Week 16) to end of Extension Period<br /><br>(Week 40) in the modified CDASI.<br /><br>* Mean change from Baseline (Week 0) to end of First Period (Week 16) and<br /><br>Extension Period (Week 40) in:<br /><br>o SF-36v2 Health Survey;<br /><br>o Individual 6 CSM used for TIS calculation.<br /><br>* Mean change in TIS from Baseline (Week 0) to end of First Period (Week 16)<br /><br>and from Baseline (Week 0) to end of Extension Period (Week 40).<br /><br>* Time to minimal, moderate and major improvement in TIS.<br /><br>* Time to confirmed deterioration in the First Period and overall.</p><br>