A global clinical study in patients with relapsing-remitting multiple sclerosis to investigate the effect of two different dose regimens of ocrelizumab compared to a placebo or Avonex by measuring the effect on brain lesions seen on MRI.

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2007-006338-32-IT
• Date of registration: 02/10/2008
• Prospective Registration: No
• Primary sponsor: F.Hoffmann-La Roche Ltd.
• Public title: A global clinical study in patients with relapsing-remitting multiple sclerosis to investigate the effect of two different dose regimens of ocrelizumab compared to a placebo or Avonex by measuring the effect on brain lesions seen on MRI.
• Scientific title: Phase II, multicenter, randomized, parallel-group, partially blinded, placebo and Avonex controlled dose finding study to evaluate the efficacy as measured by brain MRI lesions, and safety of 2 dose regimens of ocrelizumab in patients with RRMS.
• Date of first enrolment: 11/09/2008
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006338-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Belgium, Bulgaria, Canada, Czech Republic, Denmark, Finland, France, Germany, Italy, Mexico, Netherlands, Russian Federation, Spain, Switzerland, Ukraine, United Kingdom, United States

Contacts

• Name: Head of Clinical Operations
• Affiliation: Roche S.p.A

• Name: Head of Clinical Operations
• Affiliation: Roche S.p.A

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments; 2. Relapsing-remitting MS, in accordance with the revised McDonald criteria (2005); 3. Ages 18-55 years inclusive; 4. At least two documented relapses within the last 3 years prior to screening, at least one of which occurred within the last year prior to screening; 5. EDSS at baseline from 1.0 to 6.0 points; 6. Evidence of MS disease burden as defined below: a. At least six T2 lesions on an MRI scan done in the year prior to screening, based on local reading. Should an MRI scan be unavailable within the last year or showing less than six T2 lesions, a screening MRI scan* with at least six T2 lesions is required for the patient to be eligible, or b. Patient had 2 documented relapses within the year prior to screening; 7. For sexually active female and male patients of reproductive potential, use of reliable means of contraception as described below as a minimum (adherence to local requirements, if more stringent, is required): - Two methods of contraception throughout the trial, including the active treatment phase AND for 48 weeks after the last dose of ocrelizumab, or until their B-cells have repleted, whichever is longer. - Acceptable methods of contraception include one primary (e.g. systemic hormonal contraception or tubal ligation of the female partner, vasectomy of the male partner) AND one secondary barrier method (e.g. latex condoms, spermicide) OR a double barrier method (e.g. latex condom, intrauterine device, vaginal ring or pessary plus spermicide (e.g. foam, vaginal suppository, gel, cream). 8. For patients of non reproductive potential (adherence to local requirements, if more stringent, is required): a. Women may be enrolled if postmenopausal (i.e. spontaneous amenorrhea for the past year confirmed by an FSH level greater than 40 mIU/mL unless the patient is receiving a hormonal therapy for their menopause or surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy); b. Men may be enrolled if they are surgically sterile (castration)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
9. Secondary or primary progressive multiple sclerosis at screening (Visit 1); 10. Disease duration of more than 15 years in patients with an EDSS `?¤ 2.0; 11. Incompatibility with MRI (contraindications for MRI include but is not restrictive to known allergy to gadolinium contrast dyes, renal impairment which would contraindicate gadolinium injection, claustrophobia, weight `?¥ 140 kg, pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc.); 12. Contra-indications to or intolerance of oral or i.v. corticosteroids, including methylprednisolone administered i.v., according to the country label, including: a. Psychosis not yet controlled by a treatment; b. Hypersensitivity to any of the constituents; 13. Known presence of other neurologic disorders, including but not limited to, the following: a. History of ischemic cerebrovascular disorders (e.g. stroke, transient ischemic attack) or ischemia of the spinal cord; b. History or known presence of CNS or spinal cord tumor (e.g. meningioma, glioma); c. History or known presence of potential metabolic causes of myelopathy (e.g. untreated vitamin B12 deficiency); e. History or known presence of infectious causes of myelopathy (e.g. syphilis, Lyme disease, HTLV-1, herpes zoster myelopathy); f. History of genetically inherited progressive CNS degenerative disorder (e.g. hereditary paraparesis; MELAS [mitochondrial myopathy, encephalopathy, lactacidosis, stroke] syndrome); g. Neuromyelitis optica; h. History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjogren`s syndrome, Behcet`s disease); i. History or known presence of sarcoidosis; j. History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression); k. History of progressive multifocal leukoencephalopathy (PML). .... et al.


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

Health Condition(s) or Problem(s) studied

Relapsing-Remitting Multiple Sclerosis (RRMS).
MedDRA version: 14.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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

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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Avonex
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: INTERFERON BETA-1A
CAS Number: 220581-49-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Weekes 12, 16, 20 and 24.

Main Objective: To investigate the effect of ocrelizumab given as two dose regimens of 600 or 1000 mg intravenously on the total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at weeks 12, 16, 20 and 24 as compared to placebo.

Secondary Objective: `- Annualized protocol defined relapse rate by week 24; - Proportion of patients who remain relapse-free by week 24; - Total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at week 4, 8, 12, 16, 20 and 24; - Total number of new and/or persisting gadolinium-enhancing T1 lesions at week 4, 8, 12, 16, 20 and 24; - Change in total volume of T2 lesions on MRI scans of the brain from baseline to week 24; - To evaluate the safety and tolerability of 2 dose regimens of ocrelizumab compared to placebo and Avonex at week 24 and the overall safety of ocrelizumab for up to 96 weeks; -?' To investigate the pharmacokinetics and other pharmacodynamic study endpoints of ocrelizumab.

Primary end point(s): To investigate the effect of ocrelizumab given as two dose regimens of 600 or 1000 mg intravenously on the total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at weeks 12, 16, 20 and 24 as compared to placebo.

Secondary Outcome(s)

Secondary end point(s): • The annualized protocol defined relapse rate by Week 24 • Proportion of patients who remain relapse-free by Week 24 (protocol defined relapses) • The total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at weeks 4, 8, 12, 16, 20 and 24 • The total number of new and/or persisting gadolinium-enhancing T1 lesions on MRI scans of the brain at weeks 4, 8, 12, 16, 20 and 24 • Change in total volume of T2 lesions on MRI scans of the brain from baseline to Week 24.

Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20 and 24

Secondary ID(s)

WA21493

2007-006338-32-FR

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.