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Trial details
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Current status:
Approved
|
Date registered:
18/02/2022
Trial version(s)
Current: 05/11/2021
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2021114915
Protocol number
WA40404
MOH registration number
.
Trial already registered with the MoPH
Study registered at the country of origin
.
Type of registration
Prospective
Date of registration in national regulatory agency
08/11/2021
Primary sponsor
F. Hoffmann-La Roche Ltd
Primary sponsor: Country of origin
Switzerland
Public title
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Acronym
.
Scientific title
A PHASE IIIb MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF OCRELIZUMAB IN ADULTS WITH PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS
Acronym
.
Brief summary of the study: English
This study will evaluate the efficacy and safety of ocrelizumab ( Ocrevus®) compared with placebo in patients with primary progressive multiple sclerosis (PPMS), including patients later in their disease course. The primary efficacy objective for this study is to evaluate the efficacy of ocrelizumab-treated patients compared with placebo-treated patients on upper extremity disability progression. This objective is measured on upper limbs on the basis of the following endpoint: 1- upper limb disability progression defined as time to 20% worsening from baseline in 9-Hole Peg Test (9-HPT) confirmed for at least 12 weeks in all randomized patients and in patients with magnetic resonance imaging (MRI) activity (MRI activity is defined as presence of T1 gadolinium (Gd)+lesion[s] and/or new and/or enlarging T2 lesion[s] as detected by MRI scans during the screening phase). The safety objectives for this study are to evaluate the safety of ocrelizumab compared with placebo, as well as over time, for all patients who received ocrelizumab and until they receive any other immunomodulatory or immunosuppressive treatments.
Brief summary of the study: Arabic
سوف تقيّم هذه الدراسة فعّالية أوكرليزوماب ) (®Ocrevus ) وسلامته مقارنة مع الدواء الوهمي لدى مرضى التصلب المتعدد المترقي الأولي(PPMS)، بما في ذلك المرضى في مرحلة لاحقة من مراحل .المرض لديهم. الهدف الأساسي للفعالية في هذه الدراسة هو تقييم الفعالية لدى المرضى المعالجين بعقار أوكرليزوماب مقارنة بالمرضى المعالجين بالدواء الوهمي على تفاقم الإعاقة في الأطراف العلوية. يُقاس هذا الهدف على الأطراف العلوية على أساس نقطة النهاية التالية: • تفاقم الإعاقة للطرف العلوي المعرّف على أنه الوقت حتى التفاقم بنسبة 20 % من خط الأساس في اختبار بيج ذو التسع ثقوب ) 9-HPT ( المؤكد لمدة 12 أسبوعًا على الأقل في جميع المرضى الموزعين عشوائيًا وفي المرضى الذين يعانون من نشاط التصويربالرنين المغناطيسي ) (MRI )يتم تعريف نشاط التصوير بالرنين المغناطيسي على أنه وجود الجادولينيوم T1 ( Gd ( + آفة )آفات( و/أو آفة T2 جديدة و/ أو متضخمة كما تم اكتشافها بواسطة فحوص التصوير بالرنين المغناطيسي أثناء مرحلة الفرز) تتمثل أهداف السلامة لهذه الدراسة في تقييم سلامة أوكرليزوماب مقارنة بالدواء الوهمي، وكذلك مع مرور الوقت، لجميع المرضى الذين تلقواأوكرليزوماب وحتى يتلقوا أي علاجات تغيير مناعي أخرى أو علاجات مثبطة للمناعة.
Health conditions/problem studied: Specify
Primary progressive multiple sclerosis
Interventions: Specify
Eligible patients will be randomized (1:1) in a blinded fashion to either placebo or ocrelizumab. The expected sample size will be approximately 1000 patients, with at least 350 patients in the MRI active subgroup. The MRI active subgroup will consist of patients with T1 Gd+ lesion(s) and/or new and/or enlarging T2 lesion(s) as detected by MRI scan during screening. The first dose of ocrelizumab will be administered as two 300 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg infusion every 24 weeks. A minimum interval of 20 or 22 weeks, depending if the previous dose was administered in one or two infusion, should be maintained between each infusion. The first dose of placebo will be administered as two 300 mg IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single 600 mg infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending if the previous dose was administered in one or two infusion, should be maintained between each infusion.
Key inclusion and exclusion criteria: Inclusion criteria
Patients must meet the following criteria for study entry: 1-Ability to provide written informed consent and be compliant with the study protocol 2-Diagnosis of PPMS in accordance with the McDonald criteria (Thompson et al.2017). 3-Age 18-65 years at time of signing Informed Consent Form 4-Expanded Disability Status Scale (EDSS) score at screening and baseline ≥ 3.0 to 8.0, inclusive 5-Disease duration from the onset of MS symptoms relative to randomization date: Less than 20 years in patients with an EDSS score at screening 7-8.0 Less than 15 years in patients with an EDSS at screening 5.5-6.5 Less than 10 years in patients with an EDSS at screening ≤5.0 6-Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen (source documentation of laboratory results and method must be verified) - Elevated IgG index - One or more IgG oligoclonal bands detected by isoelectric focusing 7-Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands) 8-Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline 9-Neurological stability for ≥ 30 days prior to baseline. 10-Patients previously treated with immunosuppressants, immunomodulators, or other immunomodulatory therapies must undergo an appropriate washout period according to the local label of the immunosuppressant/immunomodulatory drug used. Patients screened for this study should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial. Patients who discontinue their current therapy for non-medical reasons should specifically be informed before deciding to enter the study of their treatment options and, that by participating in this study, they may be randomized to placebo for a period of 120 weeks or greater. 11-For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months (as applicable by the Ocrevus local label) after the final dose of ocrelizumab. A woman is considered to be of childbearing potential if she is post menarcheal, 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 definition of childbearing potential may be adapted for alignment with local guidelines or requirements. The following are considered adequate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; copper intrauterine devices; male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception. For female patients without reproductive potential: Women may be enrolled if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy) or post-menopausal (i.e., spontaneous amenorrhea for the past year confirmed by a follicle-stimulating hormone [FSH] level > 40 mIU/mL) unless the patient is receiving a hormonal therapy for her menopause.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
65
Key inclusion and exclusion criteria: Exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry: 1- History of relapsing-remitting or secondary progressive MS at screening 2- Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease 3- Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML) 4- Known active malignancy or are being actively monitored for recurrence of malignancy 5- Immunocompromised state, defined as one or more of the following: -CD4 count < 250/microlitre -Absolute neutrophil count <1.5 x 10^3/microlitre -Serum IgG < 4.6 g/L 6- Receipt of a live-attenuated vaccine within 6 weeks prior to randomization 7- Inability to complete an MRI (contraindications for MRI, including but not restricted to pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry in the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc.) or contraindication to Gd administration. 8- Patients requiring symptomatic treatment of MS (e.g., fampridine) and/or physiotherapy who are not on a stable regimen. Patients must not initiate symptomatic treatment of MS or physiotherapy within 4 weeks of randomization. 9- Contraindications to mandatory premedications (i.e., corticosteroids and antihistamines) for infusion-related reactions, including: -Uncontrolled psychosis for corticosteroids -Closed-angle glaucoma for antihistamines 10- Known presence of other neurologic 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 of metabolic myelopathy or known presence of untreated causes of metabolic myelopathy (e.g., untreated vitamin B12 deficiency) disease, HTLV 1, herpes zoster) History of genetically inherited progressive CNS degenerative disorder (e.g., mitochondrial myopathy, encephalopathy, lactic acidosis, stroke [MELAS]syndrome, and hereditary paraparesis) Neuromyelitis optica History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren syndrome, Behçet disease) History or known presence of sarcoidosis History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression) 11- Pregnant or breastfeeding, or intending to become pregnant during the study and for 6 or 12 months (as applicable by the Ocrevus local label) after last infusion of the study drug 12- Lack of peripheral venous access 13- Significant, uncontrolled disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study 14- Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study 15- History of alcohol or other drug abuse 16- History of primary or secondary (non-drug-related) immunodeficiency 17- Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency) 18- Previous treatment with B-cell targeting therapies (e.g., rituximab, ocrelizumab, atacicept, belimumab, ofatumumab, and alemtuzumab) 19- Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation Any previous history of transplantation or anti-rejection therapy 20- Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization 21- Systemic corticosteroid therapy within 4 weeks prior to screening The screening period may be extended for patients who have used systemic corticosteroids for MS before screening. For a patient to be eligible, systemic corticosteroids should also not have been administered between screening and baseline. 22- Positive serum beta-hCG measured at screening or positive urine beta-hCG at baseline 23- 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]) 24- Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above 25- Lack of MRI activity at screening/baseline if more than 650 patients without MRI activity have already been enrolled, as defined by T1 Gd+ lesion(s) and/or new and/or enlarged T2 lesion(s) in the screening, to ensure that at least 350 patients with MRI activity will be randomized
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
Yes, Worldwide
IMP has market authorization: Specify the countries
Europe Union
Name of IMP
OCRELIZUMAB
Year of authorization
2017
Month of authorization
3
Type of IMP
Immunological
Pharmaceutical class
Ocrelizumab is a recombinant humanized monoclonal antibody based on the human immunoglobulin (Ig) G1 framework that contains heavy chain VHIII and light chain VkI subgroup sequences.
Therapeutic indication
Primary progressive multiple sclerosis
Therapeutic benefit
In clinical trials, data from more than 5000 patients treated with ocrelizumab for autoimmune disease (that is, when the body’s immune system attacks and destroys healthy body tissue) like multiple sclerosis, rheumatoid arthritis, lupus nephritis, and systemic lupus erythematosus (an autoimmune connective tissue disease) have been analyzed. Ocrelizumab was given at doses of up to 2000 mg; the maximum dose to be given in this study is 600 mg.
Biospecimen retention
Samples with DNA**
Biospecimen description
-At participating sites, blood samples will be collected for DNA extraction to enable whole genome sequencing (WGS) or other genotype analysis to assess the patient’s germline genotype for allelic variations or mutations that are predictive of response to study drug, are associated with progression to a more severe disease state, are associated with acquired resistance to study drug, are associated with susceptibility to developing adverse events, or can increase the knowledge and understanding of disease biology. -The blood samples may be sent to one or more laboratories for analysis. -Blood samples collected for WGS are to be stored until they are no longer needed or until they are exhausted. -Patient medical information associated with WGS specimens is confidential and may be disclosed to third parties only as permitted by the Informed Consent Form (or separate authorization for use and disclosure of personal health information) signed by the patient, unless permitted or required by law.
Target sample size
1000
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
01/02/2022
Date of study closure: Type
Anticipated
Date of study closure: Date
01/02/2028
Recruitment status
Pending
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
No IPD sharing statement plan
Additional data URL
https://clinicaltrials.gov/ct2/show/NCT04035005
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
nap
nap
Sources of Monetary or Material Support
Name
F. Hoffmann-La Roche Ltd
Secondary Sponsors
Name
NAP
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT-CRO, Berytech Technology and Health, 5th Floor Damascus Road, Beirut, Lebanon
Lebanon
00961 71008269
aziz.zoghbi@mct-cro.com
Director of Country Oversight and Manageme nt MENA, Gulf and Africa
Scientific
Halim
Abboud
Hotel Dieu de France
Lebanon
00961 03535711
halim.abboud@usj.edu.lb
PI
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu de France
Halim Abboud
Neurologist
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hotel Dieu de France
26/07/2021
Nancy Choucair Alam
nancy.alam@usj.edu.lb
961 1421000-2335
Countries of Recruitment
Name
Australia
Austria
Belgium
Bulgaria
Canada
Colombia
Croatia
France
Georgia
Hungary
Ireland
Italy
Mexico
New Zealand
Poland
Portugal
Romania
Russian Federation
Republic of Serbia
Spain
Ukraine
United Kingdom
United States of America
Health Conditions or Problems Studied
Condition
Code
Keyword
Primary progressive multiple sclerosis
Multiple sclerosis (G35)
Primary progressive multiple sclerosis
Interventions
Intervention
Description
Keyword
OCRELIZUMAB
Eligible patients will be randomized (1:1) in a blinded fashion to either placebo or ocrelizumab.
Treatment
Primary Outcomes
Name
Time points
Measure
The primary efficacy objective for this study is to evaluate the efficacy of ocrelizumab-treated patients compared with placebo-treated patients on upper extremity disability progression
12 weeks from baseline
upper limb disability progression defined as time to 20% worsening from baseline in 9-Hole Peg Test (9-HPT) confirmed for at least 12 weeks in all randomized patients and in patients with magnetic resonance imaging (MRI) activity (MRI activity is defined as presence of T1 gadolinium (Gd)+ lesion[s] and/or new and/or enlarging T2 lesion[s] as detected by MRI scans during the screening phase).
Key Secondary Outcomes
Name
Time points
Measure
The secondary efficacy objective for this study is to evaluate the efficacy of ocrelizumab compared with placebo for all randomized patients
1
Upper limb disability progression defined as time to 20% increase from baseline in 9-HPT confirmed for at least 24 weeks
The secondary efficacy objective for this study is to evaluate the efficacy of ocrelizumab compared with placebo for all randomized patients
2
Time to 12-week Confirmed Disability Progression (CDP) in EDSS, defined as an increase in EDSS score that is confirmed for at least 12 weeks (an increase of ≥1.0 point from baseline EDSS score in patients with a baseline EDSS score ≤ 5.5 or an increase of ≥ 0.5 point in patients with a baseline EDSS score of > 5.5)
The secondary efficacy objective for this study is to evaluate the efficacy of ocrelizumab compared with placebo for all randomized patients
3
Time to 24-week CDP in EDSS, defined as an increase in EDSS score that is confirmed for at least 24 weeks (an increase of ≥ 1.0 point from baseline EDSS in patients with a baseline EDSS score ≤ 5.5 or an increase of ≥0.5 point in patients with a baseline EDSS score of > 5.5)
The secondary efficacy objective for this study is to evaluate the efficacy of ocrelizumab compared with placebo for all randomized patients
4
Percent change in total volume of T2 lesions from baseline up to Week 120
The secondary efficacy objective for this study is to evaluate the efficacy of ocrelizumab compared with placebo for all randomized patients
5
Percent change in total brain volume from Week 24 to Week 120
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
Download as PDF
Save a PDF copy of the summary of the trial