A Study to Evaluate Effectiveness and Safety of Ocrelizumab Treatment in Patients with Progressive Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 18 June 2018
• Main ID: EUCTR2017-001313-93-ES
• Date of registration: 02/03/2018
• Prospective Registration: Yes
• Primary sponsor: Roche Farma S.A(Soc. Unipersonal) que realiza el ensayo en España y actúa como representante de F. Hoffmann-La Roche LTD
• Public title: A Study to Evaluate Effectiveness and Safety of Ocrelizumab Treatment in Patients with Progressive Multiple Sclerosis
• Scientific title: AN OPEN-LABEL, SINGLE-ARM 4-YEAR STUDY TO EVALUATE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB TREATMENT IN PATIENTS WITH PROGRESSIVE MULTIPLE SCLEROSIS
• Date of first enrolment: 11/05/2018
• Target sample size: 600
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001313-93
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Bosnia and Herzegovina, Brazil, Canada, Colombia, Costa Rica, Czech Republic, Denmark, Egypt, France, Guatemala, Hungary, Ireland, Italy, Kuwait, Lebanon, Mexico, Morocco, Netherlands, Panama, Poland, Russian Federation, Saudi Arabia, Spain, United Arab Emirates

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
-Age 18-65 years
-Have a definite diagnosis of PMS
-Expanded Disability Status Scale (EDSS) <=6.5 at screening
- Have a length of disease duration since PMS disease symptom onset <=10 years if baseline EDSS <=5.0 and <=15 years if baseline EDSS >5.0
- Have documented evidence of disability progression independent of relapse activity at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician’s judgment
-Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist
-Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers
-For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug
-For both, PPMS patients according to revised McDonald 2010 criteria and RMS patients meeting criteria for PMS disease course as per Lublin et al. 2014, it will be documented whether or not they fulfill each of the three following McDonald Criteria:
o Evidence for Dissemination in Space (DIS) in the brain based on >=1 T2 lesion(s) in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial).
o Evidence for DIS in the spinal cord based on >=2 T2 lesions in the cord.
o Positive findings in a cerebrospinal fluid (CSF) specimen
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Relapsing-remitting multiple sclerosis (RRMS) at screening.
-Inability to complete an MRI
-Gadolinium (Gd) intolerance
-Known presence of other neurological disorders, including but not limited to, the following:
o History of ischemic cerebrovascular disorders or ischemia of the spinal cord.
o History or known presence of Central nervous system (CNS) or spinal cord tumor
o History or known presence of potential metabolic causes of myelopathy
o History or known presence of infectious causes of myelopathy
o History of genetically inherited progressive CNS degenerative disorder
o Neuromyelitis optica.
o History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease
o History of severe, clinically significant brain or spinal cord trauma
Exclusions Related to General Health
-Pregnancy or lactation
-Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressant’s during the course of the study
-History or currently active primary or secondary immunodeficiency.
-Lack of peripheral venous access.
-Hypersensitivity to ocrelizumab or to any of its excipients.
-Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study.
-Active infections must be treated and resolved before possible inclusion in the study.
-Patients in a severely immunocompromised state until the condition resolves
-Patients with known active malignancies or being actively monitored for recurrence of malignancy
-Patients who have or have had confirmed progressive multifocal leukoencephalopathy (PML)
Exclusions Related to Medications
-All vaccines should be given at least 6 weeks before the first infusion of ocrelizumab. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted
-Treatment with any investigational agent within 24 weeks of screening or five half-lives of the investigational drug or treatment with any experimental procedures for MS within 24 weeks of screening
-Previous treatment with B-cell targeted therapies
-Any previous treatment with alemtuzumab , total body irradiation, or bone marrow transplantation.
-Previous treatment with natalizumab, daclizumab or fingolimod in the last 8 weeks.
Previous treatment with natalizumab where PML has not been excluded according to a specific algorithm
-Patients previously treated with teriflunomide, unless an accelerated elimination procedure is implemented until its completion before screening visit
-Previous treatment with azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks.
-Previous treatment with mitoxantrone, cyclosporine or cladribine in the last 96 weeks.
-Contraindications to or intolerance of oral or intravenous (IV) corticosteroids, including methylprednisolone administered IV, according to the country label, such as psychosis not yet controlled by a treatment and hypersensitivity to any of the constituents
-Treatment with fampridine/dalfampridine or other symptomatic MS treatment unless on stable dose for >=30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the treatment period
Exclusions Related to Laboratory Findings
-Positive serum ß human chorionic gonadotropin (hCG) measured at screening
-Positive screening tests for hepatitis B or hepatitis C
Retesting before baseline: any

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Progressive multiple sclerosis (PMS)
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Ocrelizumab
Product Code: RO4964913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Secondary Objective: • To evaluate the effectiveness of ocrelizumab treatment in PMS patients using a range of patient-relevant measures and advanced magnetic resonance imaging (MRI) outcomes
• To evaluate the safety and tolerability of ocrelizumab in PMS patients

Main Objective: • To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course

Primary end point(s): 1. Proportion of patients with no evidence of progression sustained for at least 24 weeks (NEP)
2. Proportion of patients with NEP and no active disease (NEPAD)

Timepoint(s) of evaluation of this end point: 1-2. From baseline to Week 96, Week 96 to Week 192 and baseline to Week 192

Secondary Outcome(s)

Secondary end point(s): 1. Change from baseline in cognitive function as measured by the symbol digit modalities test
2. Change from baseline in the patient-reported outcomes including Multiple Sclerosis Impact Scale -29, Multiple Sclerosis Walking scale -12 items, ABILHAND Questionnaire, and Fatigue Scale for Motor and Cognitive (FSMC) function
3. Mean change from baseline in the EDSS score over the course of the study
4. Time to onset of first confirmed disability progression (as measured by EDSS) sustained for at least 24 weeks
5. Time to onset of first >=20% increase in timed 25-foot walk test sustained for at least 24 weeks
6. Time to onset of first >=20% increase in 9-hole peg test sustained for at least 24 weeks
7. Proportion of patients with NEP
8. Proportion of patients with NEPAD
9. Time to treatment or study discontinuation
10. Whole brain volume change
11. Cortical gray matter volume change
12. Total T2 lesion volume change
13. Slowly evolving lesion (SEL) change
14. Change in total T1 Gd+ lesion
15. Measurement of T1 gadolinium (Gd)-enhancement in new focal T2 lesions, SELs, persistent areas of non-SEL T2 lesions, and normal-appearing brain tissue
16. Cerebral white matter volume change
17. Change in Gd-enhancing fluid-attenuated inversion-recovery (FLAIR) meningeal lesions
18. Spectroscopic MR: measure of the relative signal amplitude of N-acetyl aspartate, and choline to creatine
19. Measure of phase (iron) rim lesions by T2*
20. Change in brain tissue integrity as measured by signal mass analysis
21. Rate and nature of adverse events
22. Changes in clinical laboratory results

Timepoint(s) of evaluation of this end point: 1-3. From baseline to Weeks 48, 96, 144, 192
4-6. From baseline to Week 192
7-8. From Week 24 to Week 96, Week 24 to Week 192 and Week 48 to Week 192
9. From baseline to Week 192
10-20. From baseline to Weeks 48, 96, 144, 192
21-22. From baseline to Week 192

Secondary ID(s)

MN39159

2017-001313-93-DK

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd