A multi-centre, double-blind, placebo controlled, proof of concept study to evaluate the efficacy and tolerability of BAF312 in patients with polymyositis and dermatomyositis
- Conditions
- Polymyositis and dermatomyositisMedDRA version: 9.1Level: LLTClassification code 10036102Term: PolymyositisMedDRA version: 9.1Level: LLTClassification code 10012503Term: Dermatomyositis
- Registration Number
- EUCTR2008-006311-21-HU
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 45
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. Male patients must be using two acceptable methods of contraception, (e.g., spermicidal gel plus condom) for the entire duration of the study, up to Study Completion visit, and refrain from fathering a child in the three (3) mo
1. Other types of idiopathic inflammatory myopathies (paraneoplastic PM/DM; juvenile myositis (< 18 yrs); DM with no muscle involvement; inclusion body myositis; overlap PM or DM. Pats with serological ANA, anti-dsDNA, anti-topo or clinical signs of other autoimmune diseases but not fulfilling diagnostic criteria for such connective tissue diseases are allowed to enter the study at the Investigator`s discretion. PM/DM pats with secondary Sjögren`s syndrome are eligible.
2. Myopathy due to conditions other than PM/DM.
3. Severe pharyngeal, cardiac, pulmonary involvement; any major internal organ damage which deemed clinically significant.
4. Late-stage PM/DM whose muscle weakness could be attributable to muscle damage rather than to myositis disease activity.
5. Treatment with IGs and/or mAbs within 6 mos prior to randomization: rituximab, cyclophosphamide, other immunosuppressive treatments with effects potentially lasting over 6 months, within 12 mos prior randomization.
6. Pregnant, planning to get pregnant, and/or lactating females, males planning to father a child.
7. Participation in any CT within 4 wks prior to screening or longer if required locally, for any other limitation of participation if required locally.
8. History of macular edema, diabetic retinopathy, uveitis, central serous retinophathy, retinal vein occlusion, any other eye disease that increases the risk of macular edema.
9. MI within the past 6 mos prior enrollment or current unstable ischemic heart disease, history of angina pectoris due to coronary spasm, cardiac failure at time of screening (NYHA III) or any severe cardiac disease, history of cardiac arrest or symptomatic bradycardia, resting pulse rate <55 bpm prior randomization, history of sick sinus syndrome or sino-atrial block, history or presence of any second degree AV block, or a third degree AV block or Long QT syndrome or QTc > 450 msec for males and > 470 msec for females at screening or baseline, arrhythmia requiring current treatment with class III antiarrhythmics, history of a positive tilt test during workup for vasovagal syncope, uncontrolled hypertension.
10. Severe respiratory disease, TB, except for history of successfully treated TB or history of prophylactic treatment after positive PPD skin reaction, abnormal Pulmonary Function Tests: FEV1, FVC < 70% of predicted value, DLCO < 60% of predicted value, pats receiving chronic (daily) therapies for asthma.
11. Significant drug allergy/history of atopic allergy. Hypersensitivity to study drug or similar drugs.
12. History/presence of malignancy (except successfully treated basal or squamous cell carcinoma).
13. Uncontrolled diabetes or diabetes complicated with organ involvement such as nephro- or retinopathy.
14. Systemic bacterial, viral or fungal infections, or diagnosis of AIDS, HepB, HepC.
15. Other acute or chronic infectious diseases.
16. Negative for varicella-zoster IgG antibodies at screening.
17. Have received any live or live attenuated vaccines within 2 mos prior to randomization.
18. Have received total lymphoid irradiation or bone marrow transplantation.
19. Any medically unstable condition, as assessed by the primary treating physician.
20. Surgical or medical condition significantly altering ADME of drugs or which may jeopardize patient in case of participation in the study. Investigator to be guided by evidence of any of the following: history of IBD, gastritis, ulcers, GI/rectal bleeding, history of major
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method