Relapsing-Remitting Multiple Sclerosis (RRMS) MedDRA version: 15.0 Level: LLT Classification code 10070716 Term: Multiple sclerosis pseudo relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
GlaxoSmithKline Research and Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Able to provide signed, written informed consent to participate in the study 2. 18-55 years of age. 3. Definite diagnosis of MS according to the 2010 revisions of the McDonald diagnostic criteria for MS [Polman, 2011]. 4. Subjects do not have any manifestation of another type of MS other than RRMS. 5. Subjects must have a relapsing-remitting course of disease with at least one of the following prior to screening: A. At least one confirmed relapse within the previous year or B. At least two confirmed relapses within the previous 2 years or C. At least one relapse in the previous 2 years, with a GdE brain lesion on an MRI scan in the past year. 6. Expanded Disability Status Scale (EDSS) score of 0-5.5 (inclusive) at screening. 7. Neurologically stable with no evidence of relapse for at least 30 days prior to start of Screening and during the Screening Phase (subjects who relapse during the screening Phase can be re-screened, once the relapse has resolved). 8. A female subject is eligible to enter the study if she is: A. Of non-childbearing potential B. Of childbearing potential and NOT pregnant or nursing, has a negative serum pregnancy test at screening, and agrees to one of the following: a. Complete abstinence from intercourse for the period from consent into the study until 6 months after the last dose of investigational product; or, b. Consistent and correct use of one of the following acceptable methods of birth control for the period from consent into the study until 6 months after the last dose of investigational product: i. Oral contraceptives (either combined or progesterone only) ii. Injectable progesterone iii. Levonorgestrel implants iv. Estrogenic vaginal ring v. Percutaneous contraceptive patches vi. Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of 2 years without menses. Female subjects who are post-menopausal =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria are not eligible and cannot enroll in the study: 1. Unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia,hypersensitivity to contrast media, or who lack adequate peripheral venous access). 2. Any clinically significant brain abnormality other than MS found on MRI. 3. Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) or confirmed PML (see Appendix 4, Section 11.4, for PML monitoring algorithm). 4. Subjects whom experience a relapse during the Screening Phase. These subjects may be eligible for re-screening after consultation with GSK. 5. History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral contusion, spinal cord compression) or a history or presence of myelopathy due to spinal cord compression by disk or vertebral disease. 6. Prior treatment with any of the following: A. Systemic glucocorticoids or Adrenocorticotrophic hormone (ACTH) within one month prior to screening B. Receipt of a live vaccine within 6 weeks prior to screening C. Glatiramer acetate (Copaxone) or IFN-ß (Betaferon, Betaseron, Avonex, or Rebif) within 3 months prior to screening D. Any immunomodulatory therapies, excluding glatiramer acetate or IFN-ß, within 6 months prior to screening including natalizumab and fingolimod (Gilenya), immunoglobulin, or plasma exchange/plasmapheresis E. Any monoclonal antibodies at any time, other than natalizumab (Tysabri) F. Any lymphocyte-depleting therapies, including, but not limited to: cladribine, anti-CD4, total body irradiation, or bone marrow transplantation G. Any immunosuppressive agents, including, but not limited to: mitoxantrone, azathioprine, cyclosporine, cyclophosphamide, or tacrolimus 7. Past or current history of medically significant adverse effects (including allergic reactions) from: A. Cetirizine (or equivalent) B. Paracetamol/acetaminophen C. Corticosteroids 8. Known hypersensitivity to components of the investigational product. 9. Past or current malignancy, except for A. Cervical carcinoma Stage 1B or less B. Non-invasive basal cell and squamous cell skin carcinoma C. Cancer diagnoses with a duration of complete response (remission) >5 years D. A history of hematologic malignancy excludes a subject from participation, regardless of response. 10. Electrocardiogram (ECG) showing a clinically significant abnormality at Screening or showing an average QTcB or QTcF interval =450 msec (=480 msec for subjects with a Bundle Branch Block) over 3 consecutive ECGs. 11. Significant concurrent, uncontrolled medical condition including, but not limited to, cardiac, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency syndrome, pulmonary, cerebral, psychiatric, or neurological disease which in the opinion of the investigator could affect the subject’s safety, impair the subject’s reliable participation in the trial, impair the evaluation of endpoints, or necessitate the use of medication not allowed by this protocol. 12. History of severe, clinically significant CNS trauma (e.g. cerebral contusion, spinal cord compression) or a history or presence of myelopathy due to spinal cord compression by disk or vertebral disease. 13. Chronic or ongoing active infectious disease requiring long term systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, or active hepatitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether ofatumumab 3, 30 or 60 milligrams (mg) given subcutaneously (SQ), reduces the cumulative number of new T1 GdE brain lesions over a period of 12 weeks, as compared with placebo, in subjects with RRMS;Secondary Objective: To evaluate the robustness of the MRI efficacy of ofatumumab 3, 30 or 60 milligrams (mg) given subcutaneously (SQ) over the 24 week treatment period relative to the first 12 weeks of the treatment period • To evaluate the safety and tolerability over a period of 24 weeks of a range of SQ ofatumumab doses in subjects with RRMS • To make a preliminary assessment of the efficacy of a range of SQ doses of ofatumumab in subjects with RRMS based on frequency of clinical relapses over a period of 24 weeks • To determine the extent of B-cell depletion for a range of SQ doses of ofatumumab in subjects with RRMS • To determine the extent of B-cell repletion following cessation of SQ ofatumumab treatment within specified time periods in subjects with RRMS • To evaluate the immunogenicity of SQ ofatumumab in subjects with RRMS For other study objectives please refer page12 of protocol.;Primary end point(s): Cumulative number of new T1 gadolinium-enhancing brain lesions at Week 12 from Week 0 based on MRI scans at Weeks 4, 8, and 12.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Cumulative number of new T1 Gd-enhancing brain lesions at Week 24 from Week 0 based on MRI scans at Weeks 4, 8, 12, 16, 20, and 24. •Gd-enhancing brain lesions on T1-weighted MRI based on MRI scans at Weeks 4, 8, and 12: -Cumulative number of persistent lesions at Week 12 from Week 0; -Cumulative number of all lesions at Week 12 (new plus persistent) from Week 0; -Total volume of new lesions at Week 12 (relative to Week 0); -Total volume of all lesions (new plus persistent) •T2 lesions based on MRI scans from Week 0 to Weeks 4, 8, and 12: -Cumulative number of new and/or newly enlarging lesions at Week 12; -Volume of new and/or newly enlarging T2 lesions at Week 12 •T1 hypointense lesions: -Cumulative number of new T1 hypointense lesions at Week 24 and Week 48 from Week 0; -Change from baseline in volume of T1 hypointense lesions at Week 24 and Week 48 •Change from baseline in brain volume at Week 24 and Week 48 ;Timepoint(s) of evaluation of this end point: Week 12, Week 24, and/or Week 48 | — |
Countries
Bulgaria, Canada, Czech Republic, Denmark, Germany, Italy, Netherlands, Norway, Russian Federation, Spain, United States
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline
Outcome results
None listed