Conditions: Multiple Sclerosis
Keywords: relapsing forms of multiple sclerosis ofatumumab multiple sclerosis
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 38
Healthy volunteers: no

Brief summary:
The trial consists of a dose escalation, to establish the safety of ofatumumab in RRMS patients. A 48-week treatment period followed by an individualized follow-up period until normalization of peripheral B-cell counts or Immunoglobulin G (IgG) levels.

Detailed description:
The trial consists of two phases, a 48 week treatment period, followed by an individualized treatment period of up to two years.

Patients are treated in cohorts of increasing doses (100 mg, 300 mg and 700 mg) with 12 patients in each dose cohort. Within each cohort patients are randomized asymmetrically in a 2:1 ratio such that eight patients will receive ofatumumab and four patients will receive placebo. After 24 weeks the patients randomized to placebo will be treated with the active dose for the cohort. For blinding purposes, patients randomized to the active dose will be treated with placebo after 24 weeks. Thus, each patient will receive two administrations of trial product with 24 weeks follow-up resulting in a total treatment period of 48 weeks duration. An Independent Data Monitoring Committee (IDMC) will review and evaluate the safety data of each cohort, a minimum of 4 weeks data including the week 4 Magnetic Resonance Imaging (MRI) from at least 10 patients, to consider if progression to the next higher dose cohort is acceptable.

The trial product is administered as two infusions separated by two weeks. Clinical assessment and Gadolinium enhanced (Gd-enhanced) MRI scan will be performed at weeks -4, 0, 2, 4, and every 4 weeks until week 48. The MRI scan at week 2 is carried out for safety assessment prior to administering the second infusion in the first treatment course. When patients in all dose cohorts have been dosed and have had week 4 MRI scans performed, an IDMC will review all available safety data.

After completion of week 48 patients will be followed to monitor B-cell and IgG normalization. B-cell levels will be monitored every 12 weeks until CD19+ cells have returned to baseline level (Visit 3) or normalized level. If the B-cell levels are not normalized after two years the patient should be followed until either the IgG or the B-cell levels are normalized (see Section 9.2.4 for details). During this period Gd-enhanced MRI follow up scans will be performed every 12 weeks to evaluate potential rebound, safety and for Progressive Multifocal Leukoencephalopathy (PML) monitoring.

Arms:
arm 1: 100mg ofatumumab then placebo arm 2: placebo then 100mg ofatumumab arm 3: 300mg ofatumumab then placebo arm 4: placebo then 300mg ofatumumab arm 5: 700mg ofatumumab then placebo arm 6: placebo then 700mg ofatumumab

Interventions: intervention 1: Ofatumumab 100 intervention 2: Ofatumumab 300 intervention 3: Ofatumumab 700 intervention 4: Placebo
Intervention descriptions: intervention 1: 100mg intervention 2: 300mg intervention 3: 700mg intervention 4: matching placebo

Protocol document: