Polymyositis and dermatomyositis MedDRA version: 9.1 Level: LLT Classification code 10036102 Term: Polymyositis MedDRA version: 9.1 Level: LLT Classification code 10012503 Term: Dermatomyositis
Conditions
Interventions
Product Name: BAF312 5 mg tablet
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BAF312
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration n
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients between 18-75 years who have been defined as "definite" or “probable” based on the criteria of Bohan and Peter for PM and DM at least three mo before study entry. 2. Patients must demonstrate persisting muscle weakness defined as having a score no greater than 135/150 on the baseline manual muscle testing (maximum MMT-8 score of 150) in conjunction with at least 2 other abnormal IMACS core set measures: Patient VAS with a minimum value of 2.0cm on a 10cm scale. MD global VAS with a minimum value of 2.0cm on a 10cm scale. HAQ disability index (ranging from 0 to 3) with a minimum value of 0.25. Elevation of at least one of the muscle enzymes [includes CK, LDH, ALT and AST] at a minimum level of 1.3 x the upper limit of normal. In case of ALT or AST elevation, other criteria, at the Investigator’s discretion, should be observed to ensure this is not due to liver damage. For the efficacy EP, if more than one muscle enzyme is identified as being elevated and meeting the above guidelines then the most abnormal will be selected and this enzyme will be the target enzyme followed to evaluate disease improvement or worsening. Global extramuscular disease activity score with a minimum value of 1.0 cm on a 10cm VAS scale (this measure is the physician’s composite evaluation and is based on assessments of activity scores on the constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiac scales of the MDAAT. 3. Patients must have received conventional therapies as defined by corticosteroid alone or in combination with DMARDS (MTX, AZA, CyA or MMF) for at least three months before screening. 4. Patients must be on a stable dose of corticosteroid (5-20 mg prednisone or equivalent per day) for at least 2 weeks prior to screening and should not have received a medium or high dose (= 1 mg prednisone or equivalent per body weight kg) corticosteroid therapy in the last 8 weeks prior to study entry. 5. Those patients currently treated with DMARDs must not be responding to DMARD therapy (MTX, AZA, CyA or MMF) defined by proven toxicity or inadequate efficacy as determined by the Investigator. Withdrawal from their DMARDs therapy will occur at least 4 weeks prior to baseline. 6. Female patients of child bearing potential must be using two acceptable methods of contraception (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through Study Completion. Period abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening. Female patients who report surgical sterilization must have had the procedure at least six months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History/Current Medical Conditions section of the CRF. All female patients must have negative pregnancy test results at Screening. 7. Patients must be able to communicate well with the Investigator, to understand and comply with the requirements of the study and to understand and sign the written informed consent. Are the trial subjects under 18? no Number of
Exclusion criteria
Exclusion criteria: 1. Other types of idiopathic inflammatory myopathies (paraneoplastic PM/DM; juv. myositis ( 450 msec for males and > 470 msec for females at screening or baseline ECG and/or the Screening Holter, symptomatic arrhythmia or arrhythmia requiring treatment or being otherwise of clin. significance, uncontrolled art. hypertension. Treatment with medication impairing cardiac conduction (e.g., beta blockers, verapamil-type and diltiazem-type calcium channel blockers, or cardiac glycosides), hist. of syncopes of suspected cardiac origin or catheter ablation 11. Severe respiratory disease or pulm. fibrosis, TB, except for history of successfully treated TB or history of prophylactic treatment after positive PPD skin reaction, abnormal chest x-ray or HRCT suggestive of active pulm. disease, abnormal Pulm. Function Tests: FEV1, FVC < 70% of predicted value, DLCO < 60% of predicted value, pats receiving chronic (daily) therapies for asthma 12. Significant drug allergy/history of atopic allergy. Hypersensitivity to study drug or similar 13. Hist./presence of malignancy (except successfully treated basal or squamous cell carcinoma) 14. Uncontrolled diabetes or diabetes complicated with organ involvement such as nephro- or retinopathy 15. Systemic bacterial, viral or fungal infections, or diagnosis of AIDS, HepB, HepC 16. Other acute or chronic infectious diseases 17. Neg. for varicella-zoster IgG antibodies at screening 18. Have received any live or live attenuated vaccines within 2 m prior to randomization 19. Have received total lymphoid irradiation or bone marrow transplantation 20. Any medically unstable condition 21. Surgical or med. condition significantly altering ADME of drugs or which may jeopardize patient in case of participation in the study. Investigato
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the preliminary clinical efficacy of oral BAF312 in patients with polymyositis and dermatomyositis using the IMACS core set measures. • To assess the safety and tolerability of oral BAF312 in polymyositis and dermatomyositis patients.;Secondary Objective: • To characterize the steady state PK of BAF312 in polymyositis and dermatomyositis patients. • To assess the exposure-effect relationship of BAF312 on various safety and efficacy parameters. • To assess the efficacy of BAF312 to modify health-related quality of life in polymyositis and dermatomyositis patients, as measured by SF-36. • To assess biomarkers reflecting the efficacy of BAF312 to reduce systemic inflammatory components of the disease using serum markers such as CRP and ESR . • To assess the change in steroids use after BAF312 administration (Period 2 only) in polymyositis and dermatomyositis patients.;Primary end point(s): Binary (responder/non-responder) outcome using the IMACS Definition of Improvement core set measures; patients who are known to have worsened (and consequently may drop out of the study) are treated as non-responders. | — |
Countries
Czech Republic, Hungary, Sweden, United Kingdom
Outcome results
None listed