Clinical trial NCT04544436: A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)
Official title: A Phase IIIb Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Relapsing Remitting Multiple Sclerosis; Higher Dose of CD20 Antibody Ocrelizumab; Efficacy, Safety and Pharmacokinetics
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-09-10
Enrollment: 864
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with RMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

Detailed description: Participants will be treated for a minimum of 120 weeks in the double-blind treatment (DBT) phase. Upon positive primary results after the DBT phase, an optional higher dose extension treatment, open-label extension (OLE) phase is planned for eligible participants. The OLE will be carried out for approximately 96 weeks. Participants will be followed for safety for 48 weeks thereafter. Participants whose B-cell levels still did not replete to their baseline level or the low level of normal (LLN), whichever is lower, will move into the B-cell monitoring (BCM) phase following the safety follow-up phase. The study will end when all participants who were not treated with an alternative B-cell depleting therapy have repleted their B-cells to the baseline value or the LLN.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of RMS
* At least two documented clinical relapses within the last 2 years prior to screening, or one clinical relapse in the year prior to screening. No relapse 30 days prior to screening and at baseline
* Participants must be neurologically stable for at least 30 days prior to randomization and baseline
* EDSS score, at screening and baseline, from 0 to 5.5 inclusive
* Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
* Average 9HPT score over four trials at screening and over four trials at baseline respectively, up to 250 (inclusive) seconds
* Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent with MS at screening
* Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
* Females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods
* Female participants without reproductive potential may be enrolled e.g. if post-menopausal or if surgically sterile

Exclusion Criteria:

* History of primary progressive MS at screening
* Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening
* History of confirmed or suspected progressive multifocal leukoencephalopathy
* History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
* Immunocompromised state
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
* Inability to complete an MRI or contraindication to gadolinium administration
* Contraindications to mandatory pre-medications for infusion-related reaction (IRRs)
* Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* Significant, uncontrolled disease that may preclude participant from participating in the study
* History of or currently active primary or secondary, non-drug-related, immunodeficiency
* Pregnant or breastfeeding or intending to become pregnant
* Lack of peripheral venous access
* History of alcohol or other drug abuse within 12 months prior to screening
* Treatment with any investigational agent within 24 weeks prior to screening or treatment with any experimental procedure for MS
* Previous use of anti- cluster of differentiation 20 (CD20s) (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy
* Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
* Previous treatment with natalizumab within 4.5 months of baseline
* Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
* Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab - Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication
* Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
* Any previous history of transplantation or anti-rejection therapy
* Treatment with IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization
* Systemic corticosteroid therapy within 4 weeks prior to screening
* Positive screening tests for active, latent, or inadequately treated hepatitis B
* Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
* Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above

Primary outcomes:
measure: Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12)
timeFrame: Baseline up to approximately 4.3 years
Secondary outcomes:
measure: Time to Onset of 24-week cCDP (cCDP24)
timeFrame: Baseline up to approximately 4.3 years
measure: Time to Onset of 48-week cCDP (cCDP48)
timeFrame: Baseline up to approximately 4.3 years
measure: Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR)
timeFrame: Baseline up to approximately 4.3 years
measure: Time to Onset of 12-week Confirmed Disability Progression (CDP12)
timeFrame: Baseline up to approximately 4.3 years
measure: Time to ≥ 20% Increase in 12-week Confirmed by T25FWT
timeFrame: Baseline up to approximately 4.3 years
measure: Annual Rate of Percent Change From Baseline in Total Brain Volume
timeFrame: Baseline up to approximately 4.3 years
measure: Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT)
timeFrame: Baseline up to approximately 4.3 years
measure: Time to 12-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS-12)
timeFrame: Baseline up to approximately 4.3 years
measure: Change in Neurofilament Light (NfL) at Week 48 for Participants Assigned to the Higher Dose Ocrelizumab Group
timeFrame: Baseline (Week 0), Week 48
measure: Change in NfL at Week 48 for Participants Assigned to the Approved Dose Ocrelizumab Group
timeFrame: Baseline (Week 0), Week 48
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to approximately 7.5 years
measure: Serum Concentration of Ocrelizumab at Specified Time Points
timeFrame: Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
measure: B-cell Levels in Blood
timeFrame: Baseline up to approximately 4.3 years
measure: Percentage of Participants Achieving 5 or Less B-cells per Microliter of Blood
timeFrame: Baseline up to approximately 4.3 years
measure: Change From Baseline in the Anti-drug Antibody (ADA) Levels
timeFrame: Week 0, 24, 48, 72, 96, 120
Other outcomes:
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates
state: Alabama
city: Homewood
country: United States
facility: Alabama Neurology Associates
state: Alabama
city: Phoenix
country: United States
facility: 21st Century Neurology
state: Arizona
city: Carlsbad
country: United States
facility: Profound Research, LLC
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Fort Collins
country: United States
facility: Advanced Neurology of Colorado, LLC
state: Colorado
city: Maitland
country: United States
facility: Neurology Associates, PA
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Avon
country: United States
facility: American Health Network Institute, LLC
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Alexandria
country: United States
facility: The NeuroMedical Clinic of Central Louisiana
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Center
state: Maine
city: Wellesley
country: United States
facility: Dragonfly Research, LLC
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo
state: Nevada
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Dayton
country: United States
facility: UC Health Neurology
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Johnson City
country: United States
facility: Tri-State Mountain Neurology
state: Tennessee
city: Knoxville
country: United States
facility: Hope Neurology
state: Tennessee
city: Lubbock
country: United States
facility: Bhupesh Dihenia M.D. P.A.
state: Texas
city: San Antonio
country: United States
facility: Lone Star Neurology of San Antonio
state: Texas
city: Kirkland
country: United States
facility: Evergreen MS Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Centro de Especialidades Neurológicas y Rehabilitación - CENyR
city: Buenos Aires
country: Argentina
facility: CEMIC
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Médicas Tucuman
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Bruxelles
country: Belgium
facility: Hospital Erasme
city: Overpelt
country: Belgium
facility: Revalidatie en MS Centrum
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba
state: Paraná
city: Porto Alegre
country: Brazil
facility: IMV Pesquisa Neurológica
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Clinica Neurologica
state: Santa Catarina
city: Sao Paulo
country: Brazil
facility: CPQuali Pesquisa Clinica Ltda
state: São Paulo
city: Greenfield Park
country: Canada
facility: Recherche Sepmus Inc.
state: Quebec
city: Levis
country: Canada
facility: Hotel-Dieu de Levis
state: Quebec
city: Glostrup
country: Denmark
facility: Rigshospitalet Glostrup
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin
city: Clermont Ferrand
country: France
facility: CHU Hopital Gabriel Montpied
city: Lille
country: France
facility: CH St Vincent de Paul
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: St. Josef-Hospital, Klinik für Neurologie
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Leipzig
country: Germany
facility: Universität Leipzig
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Zentrum für Neurologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wiesbaden
country: Germany
facility: Deutsche Klinik für Diagnostik
city: Athens
country: Greece
facility: 401 Military Hospital of Athens
city: Budapest
country: Hungary
facility: S-Medicon Egeszsegugyi Szolgaltato Kft.
city: Budapest
country: Hungary
facility: UNO Medical Trials Kft.
city: Kaposvar
country: Hungary
facility: Somogy Vármegyei Kaposi Mór Oktató Kórház
city: Chieti
country: Italy
facility: Universita? G. D'Annunzio
state: Abruzzo
city: Napoli
country: Italy
facility: AOU Seconda Università degli Studi
state: Campania
city: Napoli
country: Italy
facility: AOU Seconda Università degli Studi
state: Campania
city: Roma
country: Italy
facility: Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
state: Lazio
city: Roma
country: Italy
facility: NCL Institute Neuroscience
state: Lazio
city: Roma
country: Italy
facility: Policlinico Umberto I
state: Lazio
city: Milano
country: Italy
facility: Fond. Istituto Neurologico C.Besta
state: Lombardia
city: Pozzilli
country: Italy
facility: IRCCS Istituto Neurologico Neuromed
state: Molise
city: Bellavista
country: Peru
facility: Hospital IV Alberto Sabogal Sologuren
city: Lima
country: Peru
facility: Clinica Internacional
city: Lima
country: Peru
facility: Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo
city: Lima
country: Peru
facility: Hospital Maria Auxiliadora
city: Lima
country: Peru
facility: Hospital Nacional Dos de Mayo
city: Trujillo
country: Peru
facility: Clinica Sanchez Ferrer
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz sp. z o.o
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika
city: Katowice
country: Poland
facility: MA-LEK Clinical Sp. Z o.o.
city: Lodz
country: Poland
facility: SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM
city: Lodz
country: Poland
facility: Centrum Neurologii Krzysztof Selmaj
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
city: Plewiska
country: Poland
facility: Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
city: Pozna?
country: Poland
facility: EMC Instytut Medyczny SA
city: Rzeszów
country: Poland
facility: Nmedis sp. z o.o.
city: Szczecin
country: Poland
facility: Osrodek Badan Klinicznych Euromedis
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Warszawa
country: Poland
facility: Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny - Pa?Stwowy Instytut Badawczy
city: Braga
country: Portugal
facility: Hospital de Braga
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Krasnoyarsk
country: Russian Federation
facility: FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
state: Krasnojarsk
city: Sankt-peterburg
country: Russian Federation
facility: National Center of Social Significant Disease
state: Leningrad
city: Moscow
country: Russian Federation
facility: Neiro Clinica LLC
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Research Center of Neurology of RAMS
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: Federal center of brain research and neurotechnologies
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: City Clinical Hospital #24
state: Moskovskaja Oblast
city: Sankt-petersburg
country: Russian Federation
facility: N.P. Bechtereva Institute of the Human Brain
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: City Hospital #40 of Kurortniy Administrative District
state: Sankt Petersburg
city: Yekaterinburg
country: Russian Federation
facility: SHI Sverdlovsk Regional Clinical Hospital #1
state: Sverdlovsk
city: Kazan
country: Russian Federation
facility: Vertebronevrologiya LLC
state: Tatarstan
city: Kazan
country: Russian Federation
facility: KSMU Interregional Clinical Diagnostic Centre
state: Tatarstan
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
state: Uljanovsk
city: Saratov
country: Russian Federation
facility: Saratov State Medical University of RosZdrav
city: Tomsk
country: Russian Federation
facility: Nebbiolo Center for Clinical Trials
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
state: LA Coruna
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron de Madrid
state: Madrid
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga ? Hospital General
city: Basel
country: Switzerland
facility: Universitätsspital Basel Medizin Neurologie
city: Bern
country: Switzerland
facility: Inselspital Bern Medizin Neurologie
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano - Civico
city: Kocaeli
country: Turkey
facility: Kocaeli University Hospital
city: Cherkasy
country: Ukraine
facility: 5th Cherkasy City Center of Primary Health Care
city: Chernihiv
country: Ukraine
facility: Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?
city: Chernivtsi
country: Ukraine
facility: Bukovinsky SMU RMI Chernivtsi RCH
city: Dnipro
country: Ukraine
facility: SI USSRI of Medical and Social Problems of Disabilities of MOHU
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital
city: Kharkov
country: Ukraine
facility: St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU
city: Kyiv
country: Ukraine
facility: Medical Center of Private Execution First Private Clinic
city: Kyiv
country: Ukraine
facility: Medical Center Dopomoga Plus
city: Lviv
country: Ukraine
facility: Lvivska oblasna tsentralna likarnia
city: Zaporizhzhia
country: Ukraine
facility: LCC "Medical center "Unimed"
city: Zaporizhzhia
country: Ukraine
facility: Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: