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Trial details
AN OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB IN PATIENTS WITH EARLY STAGE RELAPSING REMITTING MULTIPLE SCLEROSIS
Current status:
Approved
|
Date registered:
03/06/2022
Trial version(s)
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
History: 19/03/2020
Current: 19/03/2020
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Main Information
Primary registry identifying number
LBCTR2020033434
Protocol number
MA30143
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Retrospective
Type of registration: Justify
Study started before establishment of LBCTR
Date of registration in national regulatory agency
25/01/2018
Primary sponsor
F. HOFFMANN-LA ROCHE LTD
Primary sponsor: Country of origin
Switzerland
Public title
AN OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB IN PATIENTS WITH EARLY STAGE RELAPSING REMITTING MULTIPLE SCLEROSIS
Acronym
Ensemble
Scientific title
AN OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB IN PATIENTS WITH EARLY STAGE RELAPSING REMITTING MULTIPLE SCLEROSIS
Acronym
Ensemble
Brief summary of the study: English
This study is a prospective, multicenter, open-label, single-arm effectiveness and safety study in patients with early stage RRMS. The first dose of ocrelizumab will be administered as an initial dose of two 300-mg infusions (600 mg total) in 250 mL 0.9% sodium chloride each separated by 14 days (i.e., Days 1 and 15) followed by one 600-mg infusion in 500 mL 0.9% sodium chloride every 24 weeks for the remainder of the study duration. The study will consist of the following periods: • Screening period: Up to 4 weeks • Treatment period: Open-label treatment period of 192 weeks (i.e. 24 weeks after the last dose of ocrelizumab, which will be administered at Week 168) • A follow-up period of at least 48 weeks, which is independent treatment (DMT) administered as explained below. Follow-up Period: Patients who discontinue treatment early will be followed up for at least 48 weeks after the last infusion of study drug. Patients who complete the 192 weeks Treatment Period and, in agreement with their treating neurologist, decide not to continue in a separate long term extension (LTE) study, will be followed up for at least 48 weeks after the end of the Treatment Period (i.e. 192 weeks + 48 weeks). Patients whose B-cells have not been repleted after 48 weeks of Follow-up Period will continue with visits every 24 weeks, and telephone contacts every 8 weeks, until B-cell repletion (Continued B-cell monitoring). If the patients are receiving other B-cell targeted therapies, then the Follow-up Period is only 48 weeks regardless of their B-cell count. A structured telephone interview will be conducted by site personnel every 8 weeks between the study visits (starting after the site visit at 8 weeks) during the treatment period and follow-up to identify and collect information on any changes in the patient’s health status that warrant an unscheduled visit (including new or worsening neurological symptoms) and possible events or infections.
Brief summary of the study: Arabic
ان الهدف من هذه الدراسة هو معرفة ما اذا كان اوكريليزوماب (دواء الدراسة) سيوقف تفاقم اشارات واعراض التصلّب المتعدّد المبكر. تعمل الاجسام المضادة الوحيدة النسيلة مثل جهاز مناعة المريض، وتتعلّق ببعض الخاليا بهدف الهجوم على الجراثيم وغيرها من الامراض في جسم المريض. يتعلّق اوكريليزوماب ببعض انواع كريات الدم البيضاء (الخاليا البائية) التي يعتقَد انها تلعب دوراً في مرض التصلّب المتعدّد. سوف تضّم هذه الدراسة ما لا يقّل عن 1,100 مريض. سبق ان تم اعتماد اوكريليزوماب لعلاج التصلّب المتعدد في العديد من البلدان بما فيها الواليات المتحدة االميركية واوستراليا وكندا واالتحاد االوروبي وغيرها من الدول. غير ان هذا الدواء ما زال تجريبياً في بلدان اخرى، مّما يعني ان السلطات الصحية في هذه البلدان لم تقّر استعمال اوكريليزوماب لعالج التصلّب المتعدد.
Health conditions/problem studied: Specify
This study will evaluate the effectiveness and safety of ocrelizumab in early stage relapsing-remitting multiple sclerosis (RRMS) patients.
Interventions: Specify
Ocrelizumab (Ocrevus) - recombinant humanized anti-human monoclonal antibody
Key inclusion and exclusion criteria: Inclusion criteria
Patients must meet the following criteria for study entry: • Signed informed consent form • Able to comply with the study protocol, in the investigator’s judgment • Age 18 − 55 years, inclusive • Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria (Polman et al. 2011) • Have a length of disease duration, from first documented clinical attack consistent with MS disease of ≤ 3 years • Within the last 12 months: One or more clinically reported relapse(s) OR One or more signs of MRI activity • EDSS of 0.0 to 3.5 inclusive, at screening • 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. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state ( 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The following are acceptable contraceptive methods: progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, and cap, diaphragm, or sponge with spermicide. A combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier methods) is considered acceptable.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
55
Key inclusion and exclusion criteria: Exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry: • Secondary progressive multiple sclerosis progressive relapsing MS • Inability to complete an MRI (contraindications for MRI include but are not restricted to pacemaker, cochlear implants, presence of foreign substances in the eye, 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, claustrophobia, weight>140 kg, etc.) • Known presence of other neurological disorders, including but not limited to, the following: − History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord − History or known presence of CNS or spinal cord tumor (e.g., meningioma, glioma) − History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency) − History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1 [HTLV-1], herpes zoster myelopathy) − History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis; MELAS [mitochondrial myopathy, encephalopathy, lactic acidosis, stroke] syndrome) − Neuromyelitis optica − History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjogren’s syndrome, Behçet’s disease, sarcoidosis) − History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression) UExclusions Related to General Health • Pregnancy or lactation • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study • History or currently active primary or secondary immunodeficiency • Lack of peripheral venous access • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies • Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study • Congestive heart failure (New York Heart Association [NYHA] III or IV functional severity) • Known active bacterial, viral, fungal, mycobacterial infection or other infection, (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening. Note: Active infections should be treated and effectively controlled before possible inclusion in the study • History of major opportunistic infections (i.e. cryptococcosis, Pneumocystis pneumonia, progressive multifocal leukoencephalopathy [PML]) • History or known presence of recurrent or chronic infection (e.g., human immunodeficiency virus [HIV], syphilis, tuberculosis [TB]) • History of malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been previously completely excised with documented, clear margins. • History of alcohol or drug abuse within 24 weeks prior to baseline • History or laboratory evidence of coagulation disorders UExclusions Related to Medications • Received any prior approved DMT with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate. • Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit. In rare cases when patient requires vaccination with a live vaccine, the screening period may be extended but cannot exceed 8 weeks. • Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS (e.g., treatment for chronic cerebrospinal venous insufficiency). • Contraindications to or intolerance of oral or IV corticosteroids, including methylprednisolone administered IV, according to the country label, including: a) Psychosis not yet controlled by a treatment; b) Hypersensitivity to any of the constituents. • Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab). • Systemic corticosteroid therapy within 4 weeks prior to screening. • Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone marrow transplantation). • Treatment with IV immunoglobulins (Ig) within 12 weeks prior to baseline. • Treatment with investigational DMT • History of recurrent aspiration pneumonia requiring antibiotic therapy • Treatment with fampridine/dalfamipridine (Fampyra®)/Ampyra®) unless on stable dose for ≥ 30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the 96-week treatment period. UExclusions Related to Laboratory Findings* • Positive serum β human chorionic gonadotropin (hCG) measured at screening • Positive screening tests for hepatitis B (hepatitis B surface antigen [HBsAg] positive, or positive hepatitis B core antibody [total HBcAb] confirmed by a positive viral DNA polymerase chain reaction [PCR]) • Lymphocyte count below lower limit of normal (LLN) • CD4 count<250/μL. • Aspartate aminotransferase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT) /serum glutamic pyruvic transaminase (SGPT)≥ 3.0 × the upper limit of normal (ULN) • Serum creatinine >1.4 mg/dL (> 124 μmol/L) for women or > 1.6 mg/dL (> 141μmol/L) for men • Hemoglobin < 8.5 g/dL (< 5.15 mmol/L) • Platelet count <100,000/μL (<100 × 109PP/L) • Absolute neutrophil count <1.0 × 103PP/μL
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Other
Trial scope: Specify scope
EFFECTIVENESS AND SAFETY
Study design: Allocation
N/A: Single arm study
Study design: Masking
Open (masking not used)
Study design: Control
Uncontrolled
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
Yes, Lebanon and Worldwide
IMP has market authorization: Specify the countries
United States of America, Albania, Australia, Israel, Kosovo, Kuwait, Panama, Paraguay, Russian Federation, Ukraine, United Arab Emirates, and Canada
Name of IMP
Ocrelizumab
Year of authorization
2018
Month of authorization
10
Type of IMP
Immunological
Pharmaceutical class
Ocrelizumab is a recombinant humanized anti-human monoclonal antibody that selectively targets and eliminates CD20-expressing B cells.
Therapeutic indication
Relapsing remitting multiple sclerosis
Therapeutic benefit
The majority of the clinical trials of DMTs in MS target patients who are already progressed, for example the mean duration of disease is around six years for many clinical trials (Wiendl and Meuth. 2015). There is, however, evidence suggesting that early intervention might be effective in reducing the rate of relapses in patients with RRMS and in slowing the course of MS progression (Noyes and Weinstock-Guttman. 2013). A follow-up of the phase 3 clinical trial (n = 160) of IFNβ-1a vs. placebo in early RRMS patients described above, patients randomized to IFNβ-1a (n=79) were significantly less likely to progress to an EDSS score of 4.0 or greater (44.3% vs 65.4%; P=.007) or 5.0 or greater (34.2% vs 54.3%; P=.01) than patients randomized to placebo (n=81) at the 8-year follow-up assessment (Rudick et al. 2010). Other long-term studies have also demonstrated a positive impact of early therapy in patients with RRMS. In a long-term follow-up of the pivotal PRISMS study (n=560), patients originally randomized to both the 22-μg and 44-μg doses of IFNβ-1a had sustained reductions in relapses and less disease progression compared with patients originally randomized to placebo. Although all patients received IFNβ-1a treatment by year 3 of the pivotal study (patients originally randomized to placebo were switched to either the 22- or 44-μg dose), the increased disability observed in patients for whom treatment was delayed was sustained (Kappos et al. 2006), suggesting that delaying treatment for as little as 2 years may result in irreversible consequences.
Biospecimen retention
None retained
Biospecimen description
NA
Target sample size
10
Actual enrollment target size
6
Date of first enrollment: Type
Actual
Date of first enrollment: Date
08/03/2018
Date of study closure: Type
Actual
Date of study closure: Date
16/01/2024
Recruitment status
Complete
Date of completion
21/01/2019
IPD sharing statement plan
Yes
IPD sharing statement description
During this study, health and personal information about subjects will be collected. This section describes the protection, use, and sharing of information, which consists of the following: • Information in the medical record, which is held by Sites. • Information that is collected or produced during this study ("study data"), which is held by sites, Roche, Roche affiliates, and Roche's representatives. Subject privacy is very important, and Roche uses many safeguards to protect privacy, in accordance with applicable data privacy laws and laws related to the conduct of clinical trials. Subject study data and samples will be labelled with a patient identification (ID) number that is unique and not related to or derived from information that identifies subject (such as name, picture, or any other personally identifying information). Roche, Roche affiliates, and Roche's representatives will only have access to study data and samples labelled with a patient ID number, except as described below. Subjects medical record, which includes personal information that can identify subjects, will not be accessed for the purposes of this study, except as described below: Information (which includes information in medical record that can identify subjects) may need to be reviewed to make sure the study is being done properly or to check the quality of the information. This information will be kept private. The following people and groups of people may and/or copy this information: • Study monitors of Roche and/or CRO, a company hired by Roche to perform certain study activities • The Institutional Review Board or Ethics Committee • Regulatory authorities Roche, Roche affiliates, and Roche's collaborators and licensees (people and companies who partner with Roche) may use study data labelled with patient ID number for research purposes or to advance science and public health. Study data may be submitted to government or other health research databases or shared with researchers, government agencies, companies, or other groups that are not participating in this study. These data may be combined with or linked to other data and used for research purposes, to advance science and public health, or for analysis, development, and commercialization of products to treat and diagnose disease. These data will not include information that identifies subjects, and extra steps will be taken to safeguard privacy. Subject information will not be given to insurance company or employer, unless required by law. If the results from this study are published in a medical journal or presented at a scientific meeting, subjects will not be identified. Information from this study will be retained by Sites for 15 years after the end of the study. In addition, Roche will retain the study data for up to 25 years after the end of the study.
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Sources of Monetary or Material Support
Name
Secondary Sponsors
Name
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American University of Beirut
Samia Khoury
Neuroscience
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
22/02/2021
Samia Khoury
sk88@aub.edu.lb
+961-1-350000 ext.: 5138
Countries of Recruitment
Name
Health Conditions or Problems Studied
Condition
Code
Keyword
Interventions
Intervention
Description
Keyword
Primary Outcomes
Name
Time points
Measure
Key Secondary Outcomes
Name
Time points
Measure
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Regarding the Ensemble Study, This amendment is to clarify and accurately reflect the definition of end of trial. Accordingly please find attached Cover Letter Amendment to update Definition of EoT & Memo to investigators for your kind feedback and comments
23/05/2022
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