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-GR

Lead Sponsor: ONO Pharmaceutical Co., Ltd.

Brief Summary: Not available

Detailed Description: Not available

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 =30 mL/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 me

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the safety and efficacy of ONO-4641 in patients with relapsing-remitting multiple sclerosis (RRMS) when given over a 26-week treatment period.;Secondary Objective: ;Primary end point(s): The primary endpoint will be the cumulative number of T1 weighted gadolinium (Gd)-enhanced lesions obtained with MRI at Weeks 10, 14, 18, 22 and 26. Patients who complete the treatment period or who discontinued during the treatment period and do not proceed to the extension study will enter the 4-week Follow-up Period.

Secondary Outcome Measures

Name	Time	Method

Related Trials