This study will evaluate the efficacy, safety, and pharmacokinetics of a higher dose of ocrelizumab compared with the approved dose of ocrelizumab in patients with relapsing forms of multiple sclerosis.
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy objective is to demonstrate the superiority of a higher
dose of ocrelizumab over the approved dose of ocrelizumab as assessed by risk
reduction in cCDP sustained for at least 12 weeks.
Secondary outcome
The secondary efficacy objective is to demonstrate superiority of a higher dose
of ocrelizumab over the approved dose of ocrelizumab on the basis of the
endpoints stated in protocol section 2.1.2
The exploratory efficacy objective for this study is to evaluate the efficacy
of a higher dose of ocrelizumab compared with the approved dose of ocrelizumab
on the basis of, but not limited to, the endpoints described in protocol
section 2.1.3
Background summary
Multiple sclerosis (MS) is chronic, inflammatory, demyelinating, and
degenerative central nervous system disease. The symptomatic deterioration
associated with progression of MS results in a slow, insidious loss of a
patient's motor and sensory function, as well as cognitive decline and
autonomic dysfunction. Disability progression across the spectrum of MS might
occur as a result of two concurrent inflammatory mechanisms: acute inflammation
and chronic compartmentalized inflammation.
AEven though there are many drugs currently available that target the acute
inflammatory mechanisms associated with relapses and relapse associated
worsening, to date, only ocrelizumab is indicated for PPMS
Chronic inflammation is responsible for increasing disability. This progression
of increasing disability has yet to be addressed in all forms of MS. And
treatments that can slow or stop MS disease progression are a serious unmet
medical need.
The rationale for testing a higher dose of ocrelizumab in patients with RMS and
PPMS is based on (1) exposure response analyzes in the pivotal Phase III
studies of RMS and PPMS, (2) data from Phase II study of RRMS with a higher
dose of 2000 mg ocrelizumab, and (3) data from previous phase I to III studies
with higher doses of ocrelizumab in rheumatoid arthritis (RA)
Study objective
This study will evaluate the efficacy, safety, and pharmacokinetics of a higher
dose of ocrelizumab compared with the approved dose of ocrelizumab in patients
with relapsing forms of multiple sclerosis.
Study design
Study BN42082 is a Phase IIIb, randomized, double blind, controlled, parallel
group, multicenter study to evaluate efficacy, safety and pharmacokinetics of a
higher dose of ocrelizumab (1200 mg [patient*s body weight <75 kg] or 1800 mg
[patient*s body weight
=>75 kg]) per IV infusion every 24 weeks in patients with RMS, in comparison to
the approved 600 mg dose of ocrelizumab. This study will consist of the
following phases:screening, double blind treatment (DBT) phase, open-label
extension (OLE) phase, safety follow-up (SFU), and B cell monitoring
Figure 1 (in Protocol) gives an overview of the study design
Intervention
Patients will be randomly assigned to one of two treatment arms: higher dose or
approved dose of ocrelizumab. Randomization will occur in a 2:1 ratio (higher
dose to approved dose, respectively). Randomization will be stratified.
Study burden and risks
Based on the previous experience with higher doses of ocrelizumab, ocrelizumab
MS Phase II/III exposure-safety correlation, the statistical
modeling and prediction of Serious Infections (SIE) rates in MS population from
the RA data, the higher dose of 1200 mg and 1800 mg are expected to be well
tolerated.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
• Ages 18-55 years at time of screening
• Ability to comply with the study protocol
• Diagnosis of RMS (i.e., RRMS or aSPMS where patients still experience
relapses) in accordance with the revised McDonald Criteria 2017
• At least two documented clinical relapses within the last 2 years prior to
screening, or one clinical relapse in the year prior to screening (with no
relapse 30 days prior to screening and at baseline)
• Patients must be neurologically stable for at least 30 days prior to
randomization and baseline assessments
• Expanded disability status scale (EDSS) score, at screening and baseline,
from 0 to 5.5 inclusive
• Average T25FWT score over two trials at screening and over two trials at
baseline respectively, up to 150 (inclusive) seconds
• Average 9HPT score over four trials at screening and over four trials at
baseline respectively, up to 250 (inclusive) seconds
• Documented MRI of brain with abnormalities consistent with MS at screening
• Participants requiring symptomatic treatment for MS and/or physiotherapy must
be treated at a stable dose. No initiation of symptomatic treatment for MS or
physiotherapy within 4 weeks of randomization
• For females of childbearing potential, agreement to remain abstinent or use
adequate contraceptive method.
• For female patients without reproductive potential: Females may be enrolled
if post menopausal unless the patient is receiving a hormonal therapy for her
menopause or if surgically sterile.
Exclusion criteria
• History of primary progressive MS at screening
• Any known or suspected active infection at screening or baseline, or any
major episode of infection requiring hospitalization or treatment with IV anti
microbials within 8 weeks prior to and during screening or treatment with oral
anti microbials within 2 weeks prior to and during screening
• History of confirmed or suspected progressive multifocal leukoencephalopathy
(PML)
• History of cancer, including hematologic malignancy and solid tumors,within
10 years of screening
• Immunocompromised state
• Receipt of a live or live attenuated vaccine within 6 weeks prior to
randomization
• Inability to complete an MRI or contraindication to gadolinium administration
• Contraindications to mandatory pre medications for IRRs, including
uncontrolled psychosis for corticosteroids or closed angle glaucoma for
antihistamines
• Known presence of other neurologic disorders that could interfere withthe
diagnosis of MS or assessments of efficacy and/or safety during the study
• Any concomitant disease that may require chronic treatment with systemic
corticosteroids or immunosuppressants during the course of the study
• Significant, uncontrolled disease that may preclude patient from
participating in the study
• History of or currently active primary or secondary (non-drug related)
immunodeficiency
• Pregnant or breastfeeding or intending to become pregnant during the study
• Lack of peripheral venous access
• History of alcohol or other drug abuse within 12 months prior to screening
• Treatment with any investigational agent within 24 weeks prior to screening
or treatment with any experimental procedure for MS
• Previous use of anti-CD20s (including ocrelizumab), if in the last 2 years
before screening, or if B-cell count is not normal, or if the stop of the
treatment was motivated by safety reasons or lack of efficacy
• Any previous treatment with mitoxantrone, cladribine, atacicept, and
alemtuzumab
• Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of
baseline
• Previous treatment with natalizumab within 4.5 months of baseline
• Previous treatment with interferons beta (1a or 1b), or glatiramer acetate
within 2 weeks of baseline
• Previous treatment with any other immunomodulatory or immunosuppressive
medication not already listed above without appropriate washout as described in
the applicable local label (washout to be completed prior to baseline). If the
washout requirements are not described in the applicable local label, then the
wash out period must be five times the half-life of the medication. The PD
effects of the previous medication must also be considered when determining the
required time for washout.
• Any previous treatment with bone marrow transplantation and hematopoietic
stem cell transplantation
• Any of previous history transplantation or anti-rejection therapy
• Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
• Systemic corticosteroid therapy within 4 weeks prior to screening
• Positive screening tests for active, latent, or inadequately treated
hepatitis B
• Sensitivity or intolerance to any ingredient (including excipients) of
ocrelizumab
• Any additional exclusionary criterion as per ocrelizumab (Ocrevus) local
label, if more stringent than the above
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000893-69-NL |
| CCMO | NL74512.056.20 |