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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

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ClinicalTrials.gov Identifier: NCT03560739
Recruitment Status : Recruiting
First Posted : June 18, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: OMB157 Phase 2

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.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 284 participants
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
Official Title: 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
Actual Study Start Date : September 11, 2018
Estimated Primary Completion Date : July 26, 2019
Estimated Study Completion Date : July 26, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ofatumumab

Arm Intervention/treatment
PFS (abdomen)
ofatumumab 20 mg sc. injection with PFS administrated on abdomen
Drug: OMB157
20 mg sc. injection

AI (abdomen)
ofatumumab 20 mg sc. injection with AI administrated on abdomen
Drug: OMB157
20 mg sc. injection

PFS (thigh)
ofatumumab 20 mg sc. injection with PFS administrated on thigh
Drug: OMB157
20 mg sc. injection

AI (thigh)
ofatumumab 20 mg sc. injection with AI administrated on thigh
Drug: OMB157
20 mg sc. injection




Primary Outcome Measures :
  1. Cmax between the two drug-device combinations [ Time Frame: 12 weeks ]
    Bioequivalence (Cmax) will be measured over the time period from 8-12 weeks comparing the PFS and autoinjector devices both administered to the abdomen.

  2. Area Under the Curve (AUC)tau between the two drug-device combinations [ Time Frame: 12 weeks ]
    Bioequivalence (AUCtau) will be measured over the time period from 8-12 weeks comparing the PFS and autoinjector devices both administered to the abdomen.


Secondary Outcome Measures :
  1. Cmax between the two drug-device combinations to the abdominal region and the thigh [ Time Frame: 12 weeks ]
    Characterize the pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh

  2. AUCtau between the two drug-device combinations to the abdominal region and the thigh [ Time Frame: 12 weeks ]
    Characterize the pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03560739


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, California
Novartis Investigative Site Recruiting
Fullerton, California, United States, 92835
United States, Colorado
Novartis Investigative Site Recruiting
Basalt, Colorado, United States, 81621
Novartis Investigative Site Recruiting
Boulder, Colorado, United States, 80301
United States, Florida
Novartis Investigative Site Recruiting
Miami, Florida, United States, 33136
Novartis Investigative Site Recruiting
Tampa, Florida, United States, 33609
Novartis Investigative Site Recruiting
Tampa, Florida, United States, 33612
Novartis Investigative Site Recruiting
West Palm Beach, Florida, United States, 33407
United States, Indiana
Novartis Investigative Site Recruiting
Indianapolis, Indiana, United States, 46256
United States, Missouri
Novartis Investigative Site Recruiting
Ozark, Missouri, United States, 65721
United States, Tennessee
Novartis Investigative Site Recruiting
Knoxville, Tennessee, United States, 37922
United States, Texas
Novartis Investigative Site Recruiting
Round Rock, Texas, United States, 78681
Novartis Investigative Site Recruiting
Sherman, Texas, United States, 75092
Austria
Novartis Investigative Site Recruiting
Vienna, Austria, 1010
Novartis Investigative Site Recruiting
Vienna, Austria, 1090
Czechia
Novartis Investigative Site Recruiting
Havirov, Czech Republic, Czechia, 736 01
Novartis Investigative Site Recruiting
Hradec Kralove, CZE, Czechia, 500 05
Novartis Investigative Site Recruiting
Pardubice, Czechia, 532 03
Sponsors and Collaborators
Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03560739     History of Changes
Other Study ID Numbers: COMB157G2102
First Posted: June 18, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Relapsing Multiple Sclerosis
Relapsing-remitting Multiple Sclerosis
Secondary progressive Multiple Sclerosis
Bioequivalence
Pharmacokinetics
Neurofilament light chain
Pre-filled Syringe
Auto-injector

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Ofatumumab
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Antineoplastic Agents