Ofatumumab Dose-finding in Relapsing Remitting Multiple Sclerosis (RRMS) Patients
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Ofatumumab 100; Ofatumumab 300; Ofatumumab 700; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 100mg; 300mg; 700mg; matching placebo
Intervention MeSH terms: Ofatumumab; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: relapsing forms of multiple sclerosis; ofatumumab; multiple sclerosis