A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFICACY OF ONO-4641 IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

• Conditions: Relapsing-remitting Multiple Sclerosis; MedDRA version: 12.1Level: LLTClassification code 10063399Term: Relapsing-remitting multiple sclerosis

• Registration Number: EUCTR2009-014339-19-CZ
• Lead Sponsor: ONO Pharmaceutical Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 376

Inclusion Criteria

Patients will be eligible to participate in this study if they meet all of the following criteria:
1. Male and female patients aged 18 to 55 years (inclusive) at screening (Visit 1)
2. Patients who have a definite diagnosis of relapsing remitting MS according to the 2005 revised McDonald criteria (Appendix 19.2); AND who meet at least one of the following criteria:
a. At least 2 documented relapses within previous 2 years prior to screening; OR
b. At least 1 documented relapse within the year prior to screening; OR
c. At least 1 Gd-enhanced lesion detected on locally-read MRI within 3 months prior to randomization (Visit 2);
3. Patients with a stable neurological condition who have no evidence of relapse for at least 1 month prior to screening and during the screening period and at baseline (Visit 1 and reconfirm at Visit 2);
4. Expanded Disability Status Scale (EDSS) score between 0 and 5.5 at Visits 1 and 2 (Appendix 19.3);
5. For females:
a. Female patients must prevent pregnancy or otherwise be unable to conceive as follows:
i) Surgically sterilized (e.g., hysterectomy or tubal ligation) at least 6 months prior to screening; OR
ii) Postmenopausal (defined as no menstrual bleeding for at least 1 year prior to screening and a serum follicle-stimulating hormone (FSH) level of > 40 IU/L); OR
iii) Patients of childbearing potential who agree to use an acceptable form of birth control (i.e. double barrier method; diaphragm plus condom, intrauterine device plus condom, hormonal contraception plus condom, spermicidal gel plus condom, or abstinence) from 1 month prior to the first dose until 2 months after the last dose;
b. Must not be lactating or breastfeeding within 3 months prior to screening and during the study participation;
c. Negative serum human chorionic gonadotropin (hCG) assay at screening and baseline, and negative urine hCG assay at baseline;
6. For males:
a. Surgically sterilized or agree to the use of a double-barrier method (as described above in 5.a.iii) when engaging in sexual intercourse for the period from 2 weeks before initiation of study drug administration until 2 months after the last dose;
b. Agree to refrain from sperm donation from the initiation of study drug administration until 2 months after the last dose;
7. Positive antibody enyzyme-linked immunosorbent assay (ELISA) for varicella zoster virus (chicken pox);
8. Able and willing to provide signed, written, Informed Consent;
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

Patients will not be eligible to participate in this study if any of the following criteria apply:
1. MS course other than RRMS;
2. Patients who experienced their first MS symptom more than 12 years before the screening visit;
3. Patients who have 10 or more Gd-enhanced lesions on locally-read MRI obtained during either Visits 1 or 2;
4. Diagnosis of neuromyelitis optica (NMO);
5. History of significant cardiac, hepatic, pulmonary, gastrointestinal or renal disease, immune deficiency, or any other medical conditions that would, in the investigator’s opinion, preclude therapy with ONO-4641;
6. Diagnosis of diabetes mellitus (type I or type II);
7. History of severe respiratory disease, pulmonary fibrosis or asthma requiring chronic therapy (resolved childhood asthma is permitted);
8. History of malignancy (including basal cell carcinoma);
9. History of idiopathic CD4+ T-cell lymphopenia;
10. History of clinically significant chronic disease of the immune system (other than MS);
11. History of bone marrow transplant or total lymphoid irradiation;
12. History of macular edema or macular dystrophy;
13. Active systemic bacterial, viral or fungal infections, or positive for hepatitis B (HBsAg) antigen, hepatitis C (HCV) antibody or human immunodeficiency virus (HIV-1 and HIV-2) antibody at screening;
14. Inability to undergo Gd-enhanced MRI scans;
15. Prior treatment with:
a. Alemtuzumab, rituximab, cladribine, cyclophosphamide or mitoxantrone at any time;
b. Immunosuppressive medications (including, but not limited to, azathioprine, methotrexate, mycophenolate mofetil) within 6 months prior to randomization (Visit 1 and reconfirm at Visit 2);
c. Immunoglobulins or monoclonal antibodies (including natalizumab) within 6 months prior to randomization (Visit 1 and reconfirm at Visit 2);
d. Interferon beta or glatiramer acetate within 3 months prior to randomization (Visit 1 and reconfirm at Visit 2);
e. Systemic or inhaled corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to screening;
f. Plasmapheresis therapy within 1 month prior to screening;
g. CYP3A4 inhibitors/inducers (except for rifampin) within 1 week prior to screening;
h. Rifampin within 1 month prior to screening;
i. Live vaccine within 1 month prior to randomization.
16. Any of the following abnormal laboratory values:
a. WBC < 3,500 cell/µL at screening;
b. Lymphocyte count < 800 cell/µL at screening;
c. ALT or aspartate aminotransferase (AST) > 2 × ULN at screening;
d. Creatinine >1.5 mg/dL or EGFR is =30mL/min/1.73 m2
17. Any of the following cardiovascular conditions:
a. History of symptomatic bradycardia, sick sinus syndrome, sino-atrial block, second (Mobitz type II) or third degree AV block, sustained VT, atrial fibrillation;
b. History of myocardial infarction within 6 months at screening;
c. Current unstable angina pectoris, history of angina pectoris due to coronary spasm, Raynaud’s syndrome (secondary Raynaud’s), or cardiac arrest;
d. Resting heart rate < 55 beat/min based on ECG at screening or history of any cardiac conditions that might increase the risk of a significant reduction in heart rate;
e. QTc interval > 450 msec on 12-lead ECG at screening;
f. Arrhythmia requiring current treatment;
g. Hypertension uncontrolled by medication;
18. Forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 75% of the predicted values at screening;
19. Positive on the substance abuse screen conducted at screening; (not if based on med

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified