Multiple Sclerosis Clinical Trial
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Summary
This study will evaluate the efficacy and safety of ocrelizumab ( Ocrevus®) compared with placebo in participants with primary progressive multiple sclerosis (PPMS), including participants later in their disease course. This study focuses on upper limit disability progression. This study will consist of the following phases: screening, double-blind treatment, follow-up 1 (FU1), an optional open-label extension (OLE), follow-up 2 (FU2), and B-cell monitoring (BCM).
Full Description
The screening phase will last up to 24 weeks. In the double-blind treatment phase, participants will undergo at least 120 weeks of study treatment. Study drug (ocrelizumab or placebo) will be administered every 24 weeks. In the FU1 phase, all participants who discontinue prematurely from the double-blind treatment phase will enter the FU1 phase, including participants who receive post-double progression ocrelizumab (PDP OCR) treatment, other immunomodulatory or immunosuppressive treatment(s) for MS, commercial ocrelizumab, or no treatment. The FU1 phase will run in parallel with the double-blind treatment phase until the primary analysis is performed. If the primary analysis is positive, an optional OLE phase is planned for eligible participants who either have remained in the double-blind treatment phase or are on PDP OCR treatment at the time of the primary analysis and, in the opinion of the investigator, could benefit from ocrelizumab treatment. The follow-up 2 (FU2) phase will begin after the primary analysis is performed. The following participants will move into the FU2 phase: participants who are ongoing in the FU1 and not on PDP OCR treatment at the time of primary analysis; participants who are ongoing in the double-blind treatment phase or receiving PDP OCR at the time of the primary analysis and do not enter the OLE phase; participants who complete or withdraw from the OLE phase. At the end of the FU2, all participants will move into B-cell monitoring (BCM) phase until the end of the study. This study will end when all participants who are not being treated with an alternative B-cell depleting therapy have repleted his or her B-cells.
Eligibility Criteria
Inclusion Criteria:
EDSS score at screening and baseline >= 3.0 to 8.0, inclusive
Disease duration from the onset of MS symptoms relative to randomization date:
Less than 20 years in patients with an EDSS score at screening 7.0 - 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
Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen: Elevated IgG index or one or more IgG oligoclonal bands detected by isoelectric focusing
Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands)
Neurological stability for ≥ 30 days prior to baseline
Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline
Neurological stability for >/= 30 days prior to baseline
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
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 after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
For female patients without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile
Exclusion Criteria:
History of relapsing-remitting or secondary progressive MS at screening
Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease
Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML)
Known active malignancy or are being actively monitored for recurrence of malignancy
Immunocompromised state
Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
Inability to complete an MRI or contraindication to Gd administration.
Patients requiring symptomatic treatment of MS 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.
Contraindications to mandatory premedications for infusion-related reactions, including:
uncontrolled psychosis for corticosteroids and closed-angle glaucoma for antihistamines
Known presence of other neurologic disorders
Pregnant or breastfeeding, or intending to become pregnant during the study and for 6 or 12 months after last infusion of the study drug
Lack of peripheral venous access
Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study
Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
History of alcohol or other drug abuse
History of primary or secondary immunodeficiency
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
Previous treatment with B-cell targeting therapies
Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
Any previous history of transplantation or anti-rejection therapy
Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
Systemic corticosteroid therapy within 4 weeks prior to screening
Positive serum hCG measured at screening or positive urine β-hCG at baseline
Positive screening tests for hepatitis B
Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above
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
Eligibility Criteria for Open-Label Extension Phase:
Completed the double-blind treatment phase of the trial or have received PDP OCR in the FU1 phase, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Patients who withdrew from study treatment and received another disease-modifying therapy (DMT) or commercial ocrelizumab will not be allowed to enter in the OLE phase.
Meet the re-treatment criteria for ocrelizumab
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 after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
For female patients without reproductive potential: Women may be enrolled if surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile
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There are 191 Locations for this study
Scottsdale Arizona, 85251, United States
Newport Beach California, 92663, United States
Pasadena California, 91105, United States
Washington District of Columbia, 20007, United States
Boca Raton Florida, 33487, United States
Clearwater Florida, 33761, United States
Orlando Florida, 32806, United States
Vero Beach Florida, 32960, United States
Kansas City Kansas, 66160, United States
Clinton Township Michigan, 48035, United States
Detroit Michigan, 48202, United States
Omaha Nebraska, 68198, United States
Amherst New York, 14226, United States
Columbus Ohio, 43235, United States
Columbus Ohio, 43801, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19141, United States
Greer South Carolina, 29650, United States
Houston Texas, 77030, United States
Norfolk Virginia, 23502, United States
Milwaukee Wisconsin, 53215, United States
Camperdown New South Wales, 2050, Australia
New Lambton New South Wales, 2305, Australia
Heidelberg Victoria, 3084, Australia
Parkville Victoria, 3050, Australia
Linz , 4021, Austria
Bruxelles , 1200, Belgium
Edegem , 2650, Belgium
La Louvière , 7100, Belgium
Overpelt , 3900, Belgium
Pleven , 5800, Bulgaria
Pleven , 5800, Bulgaria
Sofia , 1113, Bulgaria
Edmonton Alberta, T6G 2, Canada
Halifax Nova Scotia, B3H 4, Canada
London Ontario, N6A 4, Canada
Ottawa Ontario, K1H 8, Canada
Toronto Ontario, M5G 1, Canada
Gatineau Quebec, J8Y 1, Canada
Greenfield Park Quebec, J4V 2, Canada
Bogota , 11132, Colombia
Medellin , , Colombia
Osijek , 31000, Croatia
Varazdin , 42000, Croatia
Zagreb , 10000, Croatia
Zagreb , 10000, Croatia
Cairo , 11566, Egypt
Amiens Cedex1 , 80054, France
Bordeaux , 33076, France
Cedex , 69677, France
Clermont-ferrand , 63000, France
Colmar , 68024, France
Marseille , 13385, France
Montpellier , 34000, France
Nancy , 54035, France
Nantes , 44805, France
Nimes , 30900, France
Strasbourg , 67091, France
Tbilisi , 0114, Georgia
Tbilisi , 0141, Georgia
Tbilisi , 179, Georgia
Hannover , 30625, Germany
Kecskemet , 6000, Hungary
Tatabánya , 2800, Hungary
Dublin , Dubli, Ireland
Napoli Campania, 80131, Italy
Rome Lazio, 00133, Italy
Rome Lazio, 00189, Italy
Genova Liguria, 16132, Italy
Milano Lombardia, 20132, Italy
Pavia Lombardia, 27100, Italy
Orbassano Piemonte, 10043, Italy
Cefalù Sicilia, 90015, Italy
Achrafieh , , Lebanon
Beirut , 1107 , Lebanon
Beirut , , Lebanon
DF Mexico CITY (federal District), , Mexico
Mexico City Mexico CITY (federal District), 01600, Mexico
Mexico City Mexico CITY (federal District), 14390, Mexico
Tlalnepantla de Baz Mexico CITY (federal District), 54055, Mexico
Culiacán Sinaloa, 80020, Mexico
Chihuahua , 31203, Mexico
Chihuahua , 31238, Mexico
Durango , 34000, Mexico
Monterrey , 64050, Mexico
Marrakech , 40080, Morocco
Rabat , 10100, Morocco
Christchurch , 8011, New Zealand
Dunedin , , New Zealand
Hamilton , 3240, New Zealand
Wellington , 6021, New Zealand
Bia?ystok , 15-27, Poland
Bydgoszcz , 85-79, Poland
Gdansk , 80-80, Poland
Katowice , 40-57, Poland
Kielce , 25-72, Poland
Kraków , 31-50, Poland
Lodz , 90-32, Poland
Lublin , 20-60, Poland
Olsztyn , 10-56, Poland
Poznan , 61-73, Poland
Rybnik , 44-20, Poland
Rzeszow , 35-05, Poland
Szczecin , 70-11, Poland
Warsaw , 01-68, Poland
Warszawa , 02-95, Poland
Wroc?aw , 50-22, Poland
Almada , 2801-, Portugal
Braga , 4710-, Portugal
Loures , 2674-, Portugal
Porto , 4099-, Portugal
Torres Vedras , 2560-, Portugal
Bucharest , 02012, Romania
Bucharest , 05009, Romania
Campulung , 11510, Romania
Caracal , 23520, Romania
Constan?a , 90012, Romania
Hunedoara , 33105, Romania
Targu Mures , 54010, Romania
Barnaul Altaj, 65602, Russian Federation
UFA Baskortostan, 45000, Russian Federation
Krasnoyarsk Krasnojarsk, 66004, Russian Federation
Moscow Moskovskaja Oblast, 12536, Russian Federation
Moscow Moskovskaja Oblast, 12701, Russian Federation
Moscow Moskovskaja Oblast, 12911, Russian Federation
Moskva Moskovskaja Oblast, 10500, Russian Federation
Moskva Moskovskaja Oblast, 11153, Russian Federation
Tumen Moskovskaja Oblast, 62500, Russian Federation
Nizhny Novgorod Niznij Novgorod, 60300, Russian Federation
Nizhny Novgorod Niznij Novgorod, 60312, Russian Federation
Nizhny Novgorod Niznij Novgorod, 60313, Russian Federation
Sankt-peterburg Sankt Petersburg, 19711, Russian Federation
St. Petersburg Sankt Petersburg, 19770, Russian Federation
Yaroslavl Sankt Petersburg, 15003, Russian Federation
Saransk Saratov, 43003, Russian Federation
Yekaterinburg Sverdlovsk, 62010, Russian Federation
Kazan Tatarstan, 42004, Russian Federation
Ulyanovsk Uljanovsk, 43206, Russian Federation
Belgorod , 30800, Russian Federation
Kemerovo , 65006, Russian Federation
Kirov , 61002, Russian Federation
Nizniy Novgorod , 60315, Russian Federation
Novosibirsk , 63000, Russian Federation
Perm , 61499, Russian Federation
Tomsk , 63405, Russian Federation
Tver , , Russian Federation
Belgrade , 11000, Serbia
Belgrade , 11040, Serbia
Kragujevac , 34000, Serbia
NIS , 18000, Serbia
Nova Sad , 21000, Serbia
Uzice , 31000, Serbia
Zemun , 11080, Serbia
Majadahonda Madrid, 28220, Spain
Pozuelo de Alarcón Madrid, 28223, Spain
Vigo Pontevedra, 36204, Spain
Seville Sevilla, 41071, Spain
Barakaldo Vizcaya, 48903, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Castellon , 12004, Spain
Madrid , 28034, Spain
Madrid , 28050, Spain
Malaga , 29010, Spain
Murcia , 30120, Spain
Salamanca , 37007, Spain
Valencia , 46026, Spain
Mannouba , 2010, Tunisia
Monastir , 5000, Tunisia
Sfax , 3029, Tunisia
Tunis , 1008, Tunisia
Kyiv Chernihiv Governorate, 02123, Ukraine
Zhytomir Crimean Regional Governmenta, 10008, Ukraine
Zaporizhzhia Katerynoslav Governorate, 69035, Ukraine
Zaporizhzhia Katerynoslav Governorate, 69600, Ukraine
Zaporizhzhye Katerynoslav Governorate, 69063, Ukraine
Kharkiv Kharkiv Governorate, 61058, Ukraine
Lviv Kharkiv Governorate, 79010, Ukraine
Dnipro Kherson Governorate, 49600, Ukraine
Kherson Kherson Governorate, 73000, Ukraine
Dnipro KIEV Governorate, 49005, Ukraine
Kropyvnytskyi KIEV Governorate, 25005, Ukraine
Kyiv KIEV Governorate, 01001, Ukraine
Kyiv KIEV Governorate, 04080, Ukraine
Kyiv KIEV Governorate, 04212, Ukraine
Uzhhorod KIEV Governorate, 88018, Ukraine
Vinnytsia Podolia Governorate, 21009, Ukraine
Vinnytsia Podolia Governorate, 21050, Ukraine
Krykhivtsi Polissya Okruha, 76493, Ukraine
Kyiv , 03110, Ukraine
Kyiv , 04107, Ukraine
Lutsk , 43024, Ukraine
Cardiff , CF14 , United Kingdom
Glasgow , G51 4, United Kingdom
Inverness , IV2 3, United Kingdom
Liverpool , L9 7L, United Kingdom
London , E1 1F, United Kingdom
London , WC1N , United Kingdom
Nottingham , NG7 2, United Kingdom
Plymouth , PL6 8, United Kingdom
Salford , M6 8H, United Kingdom
Sheffield , S10 2, United Kingdom
Swansea , SA6 6, United Kingdom
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