A 12 Week Randomized Open Label Parallel Group Multicenter Study to Evaluate Bioequivalence of 20 mg Subcutaneous Ofatumumab Injected by Pre-filled Syringe or Autoinjector in Adult RMS Patients

Characterization of the pharmacokinetics of ofatumumab administered via the PFS used
inclinical trials and the to-be-marketed autoinjector at the clinical dose of 20 mg will be
conducted after an initial depletion of CD20 positive B-cells. Comparing the ofatumumab
pharmacokinetics between the two drug-device combinations only after the induction period is
expected to reduce initial high variability due to target-mediated clearance. This ensures a
more stable baseline for PK comparison in a parallel group study design and reflects the
clinical situation where systemic concentrations are at steady-state. In order to justify the
resulting longterm B-cell depletion, a PK comparability study between the PFS and the AI can
only be conducted in MS patients rather than in healthy subjects to balance the risk/benefit
and to obtain PK data from the relevant patient population. In order for patients to obtain a
clinical benefit from participation in the study, continued treatment with ofatumumab will be
offered to all eligible patients through enrollment into the open-label Phase 3 extension
study (separate protocol, COMB157G2399).

A secondary objective of the study is to characterize the pharmacokinetics following
subcutaneous administration of ofatumumab to either the abdominal region or the thigh which
are two injections sites allowed in the Phase 3 study and planned for inclusion in the label.
Another secondary objective is assessment of immunogenicity during the 12 weeks duration of
the study addressing potential differences in ofatumumab anti-drug antibody formation between
the PFS and AI devices as well as between abdomen and thigh injection sites.

An exploratory objective of the study includes evaluation of the PK and PD during the
induction phase in order to obtain an improved understanding of the time-course of the
initial depletion of CD20-positive B-cells and to establish an improved data source for PK/PD
modelling. An additional exploratory objective of the study will be a feasibility assessment
of using Neurofilament Lightchain (NfL) concentrations to estimate early response of NfL to
treatment initiation and to estimate the relative timing of NfL increases and the occurrence
of Gd-lesions on MRI.

Inclusion Criteria:

- Diagnosis of multiple sclerosis (MS)

- Relapsing MS: relapsing-remitting course (RRMS), or Secondary progressive (SPMS)
course

- EDSS score of 0 to 5.5

- Documentation of at least: 1 relapse during the previous year OR 2 relapses during the
previous 2 years prior to Screening OR a positive Gd-enhancing MRI scan during the
year prior to randomization.

- Neurologically stable within 1 month prior to randomization

Exclusion Criteria:

- Patients with primary progressive MS or SPMS without disease activity

- Disease duration of more than 10 years in patients with EDSS score of 2 or less

- Patients with an active chronic disease of the immune system other than MS

- Patients with active systemic bacterial, viral or fungal infections, or known to have
AIDS or to test positive for HIV antibody at Screening

- Patients with neurological findings consistent with Progressive Multifocal
Leukoencephalopathy (PML), or confirmed PML Other protocol-defined inclusion/exclusion
criteria may apply