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: 14 March 2022
• Main ID: EUCTR2007-006338-32-BG
• Date of registration: 31/07/2008
• Prospective Registration: Yes
• Primary sponsor: Hoffman 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 relapsing-remitting multiple sclerosis
• Date of first enrolment: 07/10/2008
• 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: yes; Other trial design description: Main study parallel group, partially blind, now in open label extension; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments;
2. RRMS, in accordance with the revised McDonald criteria (2005);
3. Ages 18-55 years,
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 recent MS activity 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:
- Two methods of contraception throughout the trial, including the active treatment phase AND for females, for 24 weeks after the last dose of ocrelizumab, or until their B-cells have repleted, whichever is the 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)) may be used.
8. For patients of non reproductive potential:
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.
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 200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Secondary or primary progressive MS at screening
2. Disease duration > 15 years in patients with an EDSS = 2.0
3. Incompatibility with MRI
4. Contra-indications to or intolerance of oral or i.v. corticosteroids, including methylprednisolone administered i.v., according to the country label
5. Known presence of other neurologic disorders, including but not limited to, the following:
- History of ischemic cerebrovascular disorders or ischemia of the spinal cord
- History or known presence of CNS or spinal cord tumor, potential metabolic causes of myelopathy, infectious causes of myelopathy, history of genetically inherited progressive CNS degenerative disorder, Neuromyelitis optica, history or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease, history or known presence of sarcoidosis, history of severe, clinically significant brain or spinal cord trauma, history of progressive multifocal leukoencephalopathy

Exclusions Related to General Health:
1. Pregnancy or lactation
2. Lack of peripheral venous access
3. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
4. Significant, uncontrolled disease, such as cardiovascular, cardiac arrhythmia, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine or gastrointestinal
5. Congestive heart failure NYHA III or IV functional severity
6. Known active bacterial, viral, fungal, mycobacterial infection or other infection [including tuberculosis [TB] or atypical mycobacterial disease (but excluding fungal infection of nail beds)] or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
7. History or known presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis, tuberculosis)
8. History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix of the uterus that have been excised and resolved)
9. History of alcohol or drug abuse within 24 weeks prior to randomization
10. History of or currently active primary or secondary immunodeficiency
11. History or laboratory evidence of coagulation disorders

Exclusions Related to Medications
1. Treatment with any investigational agent within 4 weeks of screening or five half-lives of the investigational drug (whichever is longer)
2. Receipt of a live vaccine within 6 weeks prior to randomization

Exclusions Related to Medications Potentially Used for the Treatment of MS
1. Incompatibility with Avonex use (see protocol)
2. Previous treatment with rituximab
3. Previous treatment with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, cladribine, cyclophosphamide, total body irradiation, bone marrow transplantation) except mitoxantrone which should not be used within 48 weeks prior to randomization
4. Treatment with lymphocyte trafficking blockers (e.g. natalizumab, FTY720) within 24 weeks prior to randomization
5. Treatment with beta interferons, glatiramer acetate, i.v. Immunoglobulin (i.v. Ig), plasmapheresis, or immunosuppressive therapies (e.g., mycophenolate mofetil [MMF], cyclosporine or azathioprine) within 12 weeks prior to randomization
6. Systemic corticosteroid therapy within 4 weeks prior to randomization

Exclusions Related to Laboratory Findi

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

Health Condition(s) or Problem(s) studied

Multiple sclerosis is a disabling disease of brain and spinal cord that disrupts flow of information within brain, characterized by flare-ups with periods of remission in between (relapsing remitting)
MedDRA version: 21.1 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)

Trade Name: Avonex
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: INTERFERON BETA-1A
Other descriptive name: INTERFERON BETA-1A
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 30-

Product Name: Ocrelizumab 300mg
Product Code: RO4964913/F07
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: oclelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Ocrevus
Product Name: Ocrelizumab 300mg
Product Code: RO4964913/F07
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

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.

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

Main Objective: The primary objective in this study is 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 with placebo.

Secondary Objective: - The annualized protocol defined relapse rate by Week 24;
- Proportion of patients who remain relapse-free by Week 24;
- 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;
- To evaluate the safety and tolerability of two dose regimens of ocrelizumab in patients with RRMS as compared with placebo and Avonex at Week 24 and the overall safety of ocrelizumab administered for up to 96 weeks;
- To investigate the pharmacokinetics and other pharmacodynamic study endpoints of ocrelizumab.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are:
• 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 AG

Ethics review

Status: Approved
Approval date: 17/07/2008
Contact:

Results

• Results available: Yes
• Date Posted: 22/03/2015
• Date Completed: 09/03/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-006338-32/results