To demonstrate that ofatumumab is superior to teriflunomide in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Annual Relapse Rate (ARR)
* Time to disability worsening as measured by 3-month confirmed worsening
(3mCDW) on Expanded Disability Status Scale (EDSS)
* Time to disability worsening as measured by 6-month confirmed worsening
(6mCDW) on EDSS
* Time to disability improvement as measured by 6-month confirmed improvement
(6mCDI) on EDSS
* Number of T1 gadolinium (Gd)-enhancing lesions per Magnetic Resonance Image
(MRI) scan
* Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion
rate)
* Neurofilament light chain (NfL) concentration in serum
* Rate of brain volume loss (BVL) based on assessments of percentage brain
volume change from baseline
Secondary outcome
* Time to first relapse
* Annualized relapse rates > 8 weeks after the onset of treatment
* Risk of a 3mCDW > 8 weeks after the onset of treatment
* Risk of a 6mCDW > 8 weeks after the onset of treatment
* Time to a 6-month confirmed cognitive decline (6mCCD), defined as a 4-point
worsening on Symbol Digit Modalities Test (SDMT)
* Time to 6mCDW or 6mCCD, whichever is reached first
* Change in cognitive performance relative to baseline as measured by the SDMT
* Time to 6-month confirmed worsening of at least 20% in the timed 25 foot walk
test (T25FW)
* Time to 6-month confirmed worsening of at least 20% in the 9-hole peg test
(9HPT)
* Time to 6mCDI sustained until end of study as measured by EDSS
* Number of new or enlarging T2 lesions between Month 12 and End of Study (EOS)
* Change in T2 lesion volume relative to baseline
* Proportion of patients with no evidence of disease activity (NEDA) at year 1
and 2
* Physical and psychological impact of MS disease as measured by the Multiple
Sclerosis Impact Scale (MSIS-29)
In the subgroup of newly diagnosed, treatment-naïve patients, evaluate if:
* High NfL (above median) concentration at baseline is predictive of higher
disease activity post baseline
* Patients with a high NfL (above median) concentration at baseline benefit
from a stronger relative treatment effect of ofatumumab vs teriflunomide
* The safety profile of ofatumumab vs terifluomide is comparable in patients
with high NfL (above median) concentration at baseline
* To evaluate the safety and tolerability of ofatumumab compared to
teriflunomide
* To evaluate the pharmacokinetic (PK) of ofatumumab
Background summary
Multiple sclerosis is a chronic condition in which the central nervous system
is affected. Inflammations occur in the nervous tissue with the result that the
transfer of information is affected in the central nervous system, and nerves
die off. As a result, the patient experiences more and more physical symptoms,
this leads to serious limitations. It is therefore important to start with an
effective treatment at an early stage to prevent permanent damage. Currently,
the MS treatment consists of medication that primarily focusses on the T cells.
Recent research has shown that not only the T-cells of the immune system play a
role in the damage of the nervous system, but also the B-cells. B-cells have an
essential function mainly in the early phase of an immune response, a.o. by the
regulation of T-cells and inflammation via the production of cytokines. B-cells
are present in the inflammatory lesions in the nervous system and in the
cerebrospinal fluid of patients with MS.
Ofatumumab, a fully human anti-CD20 monoclonal antibody, has a similar
mechanism of action as rituximab and ocrelizumab and is already registered for
the treatment of patients with chronic lymphocytic leukemia in a higher dosage
(under trade name Arzerra*). As a fully human antibody ofatumumab is predicted
to have a reduced immunogenicity, partly supported by the very low incidence of
anti-drug antibodies against ofatumumab observed in clinical trials (<1% of
patients in the oncology studies). In addition, results from two Phase 2
studies in patients with MS show that subcutaneous administration of ofatumumab
reduces the number of active inflammation with more than 90% (in 4-12 week
after the start of the study).
In this phase 3 study, the effects (efficacy, safety and tolerability) of
ofatumumab compared to the active comparator teriflunomide for the maximum
period of 2.5 years. Teriflunomide (trade Aubagio®) is registered in the
Netherlands as a treatment for relapsing-remitting MS. The study is followed by
an open-label extension study in which all patients are treated with ofatumumab
with the objective to investigate the long term safety and tolerability of
ofatumumab.
There are no risky surgeries. Unlike a regular treatment is extra bled, are
purchased more neurological tests and questionnaires are completed. ECG is made
also.
The risk to the patient is limited to the risk of side effects of the study
medication and injection. All participating patients are treated with an active
agent. The burden on the patient is acceptable.
Given the need for more opportunities to treat relapsing MS, it is justified to
ask patients to participate in this study
Study objective
To demonstrate that ofatumumab is superior to teriflunomide in reducing the
frequency of confirmed relapses as evaluated by the annualized relapse rate
(ARR) in patients with relapsing MS
Study design
Randomized, double-blind, double-dummy, parallel-group, active-comparator
controlled, adaptive design, maximal treatment duration of 30 months for an
individual patient
Intervention
Ofatumumab (OMB157G) 20 mg sc injections once every 4 (q4) weeks (following
initial loading regimen of three 20 mg sc doses/week in first 14 days) +
teriflunomide-matching placebo capsules orally once daily
Teriflunomide 14 mg capsules orally once daily + ofatumumab-matching sc placebo
injections
Study burden and risks
Risks: Adverse events of study medication (ofatumumab and teriflunomide) and
methylprednisolon (evt. given before first and following injections study
medication) and study assessments (drawing of blood, injecitons)
Burden:
Visits: screening, baseline, Day 1, 7 and 14, Month 1, 3, then every three
months.
Physical examination at screening, baseline, every 6 months
Blood pressure, weight each visit
Blood tests: each visit plus extra for required safety testing during treatment
with terflunomide (biweekly fisrt half a year) and then bimonthly
Pregnancy tests; during screening and final visit by a blood test, on day 1
every 3 months through urinalysis
ECG at screening or baseline and the final visit
MRI screening, annually
Neurological examination (EDSS) assessment, baseline or day 1 every 3 months
T25W: screening or baseline, every 3 months
9-HPT and SDMT: screening or baseline, every 6 months
Questionnaires: Screening or Baseline, then every visit
Call every month if no visits scheduled
Diary if necessary
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
* Male or female patients aged 18 to 55 years (inclusive) at Screening
* Relapsing MS: relapsing-remitting course (RRMS), or secondary progressive (SPMS) course with disease activity
* Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive)
* Documentation of at least: 1 relapse during the previous 1 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
* Patients meeting criteria for neuromyelitis optica
* Disease duration of more than 10 years in patients with an EDSS score of 2 or less
* Women of child-bearing potential unless using highly effective methods of contraception during study drug dosing and for 12 months post-dosing
* Sexually active males unless they agree to use condom during intercourse while on study drug
* Patients at risk of developing or having reactivation of hepatitis: positive results at Screening for serology markers for hepatitis A, B, C and E (HA, HB, HC, and HE) indicating acute or chronic infection
* Patients at risk of developing or having reactivation of syphilis or tuberculosis
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 | EUCTR2015-005418-31-NL |
| ClinicalTrials.gov | NCT02792218 |
| CCMO | NL58118.029.16 |