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
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary purpose of this study is to demonstrate pharmacokinetic bioequivalence of
      ofatumumab injected by Pre-filled Syringe (PFS) versus Auto-Injector (AI) devices and thereby
      establish a bridge between the ongoing Phase 3 program and the to-be-marketed drug-device
      combinations
    

Detailed description: 
      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.

      This was a randomized, open-label, multi-center, parallel group 12-week study to evaluate the
      pharmacokinetic bioequivalence of ofatumumab injected by pre-filled syringe (PFS) or
      autoinjector (AI) devices. The study design included four parallel groups of relapsing
      multiple sclerosis (RMS) patients. Assessment of the primary and secondary endpoints was
      based on data collected through the dosing interval between Week 8 and Week 12 where
      approximate steady-state pharmacokinetics was anticipated.

      All patients received open-label ofatumumab 20 mg sc every 4 weeks (after an initial loading
      regimen of three weekly 20 mg doses in the first 14 days) and were randomized (5:5:1:1) into
      4 groups dependent on device and location of injection. Randomization was not blinded.
      Groups: 1: PFS, abdomen, 2: AI, abdomen 3: PFS, thigh 4: AI, thigh.

      The study had 3 Parts. Part 1 was a 30 day screening period. Part 2 was a treatment period
      which had an induction period of 4 weeks, followed by 4 weeks to ensure steady state was
      reached and a 4 week pharmacokinetics phase for a total of 12 weeks.

      Part 3 was a safety follow-up period for patients who completed the study but did not enter
      the extension study and patients who prematurely discontinued the study. This period was 9
      months for patients who had repleted their B-cells (back to baseline value). For patients who
      had not repleted their B-cells, 3 month assessments were done until their B-cells were
      repleted or patients had initiated other disease modifying/immunosuppressive thereapy.
    

Intervention name(s): ofatumumab with PRF; ofatumumab with AI
Intervention type(s): Combination Product; Combination Product
Intervention description(s): ofatumumab 20 mg subcutanious injection administered with pre-filled syringe (PRF); ofatumumab 20 mg subcutaneous injection administered with autoinjector (AI)
Intervention MeSH terms: Ofatumumab; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: To address the primary objective of testing bioequivalence at dosing interval after Week 8 between Pre-filled Syringe (PFS) and Auto-Injector (AI), the primary analysis involves the two groups (PFS (abdomen) and AI (abdomen)). Further the pharmacokinetcs of ofatumumab will be compared between using the thigh or abdomen for injections.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Relapsing Multiple Sclerosis; Relapsing-remitting Multiple Sclerosis; Secondary progressive Multiple Sclerosis; Bioequivalence; Pharmacokinetics; Neurofilament light chain; Pre-filled Syringe; Auto-injector; adult; AI; PFS; OMB157