Relapsing-remitting multiple sclerosis MedDRA version: 9.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis
Conditions
Interventions
Product Name: AIN457
Product Code: AIN457
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: not available
CAS Number: not availabl
Current Sponsor code: AIN457
Other descripti
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients age 18 to 55 years of age included. 2. Females of childbearing potential: • must be using two highly effective methods of contraception, (e.g., hormonal contraception plus condom, 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 and for 16 weeks following study completion. Periodic 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. • All female patients must have negative pregnancy test results at screening and Week 0 (Day 1). • If female patients have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing. 3. 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 the Study Completion visit, and refrain from fathering a child in the 16 weeks following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. 4. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. 5. Diagnosis of MS as defined by revised McDonald criteria (Polman, et al 2005; Appendix 5) 6. A relapsing-remitting course of disease with a. at least 1 documented relapse during the previous year, or b. 2 documented relapses during the previous 2 years, or c. a positive Gd-enhanced MRI scan at screening 8. An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at screening 9. No evidence of a relapse within 30 days prior to randomization. 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A manifestation of another type of MS than RRMS 2. Have been treated with: a. systemic corticosteroids or ACTH for relapses within 1 month prior to randomization b. IFN-ß or glatiramer acetate within 1 month prior to randomization c. immunosuppressive medications such as azathioprine or methotrexate within 16 weeks prior to randomization d. immunoglobulins and/or monoclonal antibodies (including natalizumab and rituximab) within 6 months prior to randomization, but only if the immunosuppressive effects are not likely to persist at randomization 3. Have received total lymphoid irradiation, bone marrow transplantation, alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, or other immunosuppressive treatments with long-lasting (over 6 months) or permanent effects. 4. Have received any live or live attenuated vaccines (including live vaccines for varicella-zoster virus or measles) within 2 months prior to randomization 5. History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome 6. History of severe hypersensitivity to any biological agents (antibody or soluble protein) or a history of other serious allergic reactions. History of hypersensitivity to natural or recombinant interferon beta or human albumin or to any of other interferon beta excipients 7. Current severe depression and/or suicidal ideation 8. Pregnant or nursing (lactating) women 9. History or presence of malignancy (except for successfully-treated basal or squamous cell carcinoma of skin) 10. A known history of diabetes mellitus requiring drug treatment, or ‘new’ diagnosis of diabetes mellitus (if screening blood glucose is suspicious for diabetes [= 126 mg/dL or = 7 mmol/L if fasting; = 200 mg/dL or 11.1 mmol/L if random testing] a patient should be further evaluated for diabetes mellitus). An uncomplicated and stable diabetes mellitus type 2 (as judged by the primary treating physician), treated with diet alone, is not an exclusion criteria 11. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively (reconfirmation may be done in case of suspected false positive result) 12. Positive Purified Protein Derivative (PPD) tuberculin skin test (according to local guidelines) at screening or 6 months prior to screening. 13. Subjects with active or history of clinically significant cardiac abnormalities, 14. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), ?-GGT, alkaline phosphatase, or serum bilirubin. 15. Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/randomization, to rule out lab error 16. If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin. In any case, serum bilirubin should not exceed the value of 1.6 mg/dL (27 µmol/L) 17. History of renal trauma, glomerulonephritis, or patients with one kidney 18. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing or longer if required by local regulation 19. Unable or unwilling to undergo multiple venipunctures because o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of AIN457 (10 mg/kg i.v.) administered week 0, 2, 4, 8, 12, 16 and 20 compared to placebo on the number of combined unique active lesions (CUAL) observed on brain MRI scans performed every 4th week from week 4 to week 24 in patients with relapsing-remitting multiple sclerosis (RRMS). CUAL is defined as: new gadolinium [Gd]-enhanced lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting.;Secondary Objective: • To evaluate the safety and tolerability of AIN457 during 24 weeks of treatment in patients with RRMS • To evaluate the effect of AIN457 on the number of relapses and thereof derived measures (e.g. annualized relapse rate (ARR), proportion of relapse-free patients) ;Primary end point(s): The primary endpoint is the number of CUAL during 24 weeks of treatment. It will be analyzed by means of a negative binomial regression model with factor ‘treatment’ (AIN457, placebo) and covariate ‘Gd-enhancing T1 lesions at baseline’ using the log link function and assuming a negative binomial distribution for the target variable. | — |
Countries
Czech Republic, Sweden
Outcome results
None listed