A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)

Multiple Sclerosis Clinical Trial

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 Primary Progressive Multiple Sclerosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04548999
• Other study ID #: BN42083
• Secondary ID: 2020-000894-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 3, 2020
• Est. completion date: March 8, 2029

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and pharmacokinetics of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks in participants with PPMS, in comparison to the approved 600 mg dose of ocrelizumab.

Description:

Participants will be treated for a minimum of 120 weeks in the double-blind phase. Upon positive primary results after the double-blind phase, an optional higher dose extension treatment (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 lower limit 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 lower limit of normal.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 769
• Est. completion date: March 8, 2029
• Est. primary completion date: April 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Diagnosis of primary progressive multiple sclerosis (PPMS).

• Expanded disability status scale (EDSS) score at screening and baseline, from 3 to 6.5 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 (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds

• Score of >/= to 2.0 on the Functional Systems scale for the pyramidal system that was due to lower extremity findings at screening and baseline.

• Documented MRI of brain with abnormalities consistent with MS

• 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.

• Participants must be neurologically stable for at least 30 days prior to randomization and baseline.

• Disease duration from the onset of MS symptoms; if EDSS score at screening is less or equal to 5, disease duration must be less than 10 years; If EDSS score at screening is more than 5, disease duration must be less than 15 years

• Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands.

• 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 relapsing remitting or secondary 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 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 or treatment with any experimental procedure for MS.

• Previous use of anti-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.

• Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab

• 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

• 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 intravenous (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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Sclerosis

Intervention

Drug:
• Ocrelizumab
The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (participants's body weight <75 kg) or 1800 mg (participant's body weight >/=75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion every 24 weeks. During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total)
• Ocrelizumab
Ocrelizumab will be administered at a dose of 600 milligram (mg) every 24 weeks. The first dose of ocrelizumab will be administered as two 300 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion every 24 weeks.
• Antihistamine
Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.
• Methylprednisolone
Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Locations

Country	Name	City	State
Argentina	CEMIC Saavedra	Buenos Aires
Argentina	Centro de Especialidades Neurológicas y Rehabilitación - CENyR	Buenos Aires
Argentina	INECO; Neurociencias	Rosario
Belgium	Revalidatie en MS Centrum	Overpelt
Brazil	L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar	Brasilia	DF
Brazil	Hospital das Clinicas - UNICAMP	Campinas	SP
Brazil	Instituto de Neurologia de Curitiba	Curitiba	PR
Brazil	Hospital das Clinicas - UFG	Goiania	GO
Brazil	Clinica Neurologica; Neurocirurgica de Joinville	Joinville	SC
Brazil	Instituto Méderi de Pesquisa e Saúde	Passo Fundo	RS
Brazil	Hospital Moinhos de Vento	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	IMV Pesquisa Neurológica	Porto Alegre	RS
Brazil	Praxis Pesquisa Médica	Santo Andre	SP
Brazil	CPQuali Pesquisa Clinica Ltda	Sao Paulo	SP
Bulgaria	UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases	Pleven
Bulgaria	MHATNP Sveti Naum EAD	Sofia
Canada	Chum Campus Notre Dame	Montreal	Quebec
Canada	MUCH - Montreal Neurological Institute & Hospital	Montreal	Quebec
Canada	Hotel-Dieu de Levis	Quebec
Denmark	Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.	Aalborg
Denmark	Rigshospitalet Glostrup; Neurologisk Klinik	Glostrup
France	CHU de Besancon Hopital Jean Minjoz; Service de Neurologie	Besançon
France	CHU Brest Hopital La Cavale Blanche; Neurologie	Brest
France	Hopital Cote De Nacre; Unite Neurologie Generale	Caen
France	CHU Hopital Gabriel Montpied; Service de Neurologie	Clermont Ferrand
France	CH St Vincent de Paul	Lille
France	Hopital Central - CHU de Nancy; Service de Neurologie	Nancy
France	Hopital Hautepierre - CHU Strasbourg; Service de Neurologie	Strasbourg
Germany	Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften	Dresden
Germany	Universitätsmedizin Greifswald; Klinik und Poliklinik für Neurologie	Greifswald
Germany	Medizinische Hochschule Hannover, Klinik für Neurologie	Hannover
Germany	Universität Leipzig; Innere Medizin, Neurologie, Dermatologie	Leipzig
Germany	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster
Germany	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
Germany	Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie	Wiesbaden
Greece	401 Military Hospital of Athens; Neurology Department	Athens
Greece	Hospital Eginition; First Department of Neurology	Athens
Greece	University General Hospital of Larisa; Neurology Clinic	Larisa
Greece	AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.	Thessaloniki
Hungary	Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet; Neurology	Budapest
Hungary	UNO Medical Trials Kft.	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz; Neurologiai Osztaly	Gyor
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz; Department of Neurology	Kaposvár
Hungary	Kistarcsai Flor Ferenc Korhaz; Neurology and Stroke Ambulance	Kistarcsa
Italy	Ospedale S.Antonio Abate; Neurologia 2 ? Sclerosi Multipla e Recupero Neurologico	Gallarate	Lombardia
Italy	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia
Italy	A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche	Napoli	Campania
Italy	AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica	Napoli	Campania
Italy	IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla	Pavia	Lombardia
Italy	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio
Italy	AOU Città della Salute e della Scienza; Neurologia 1	Torino	Piemonte
Mexico	Grupo Médico Camino S.C.	Ciudad de México	Mexico CITY (federal District)
Mexico	Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.	Guadalajara	Jalisco
Mexico	Clinstile S.A de C.V.	Mexico City	Mexico CITY (federal District)
Mexico	Neurociencias Prisma, A.C	San Luis Potosí	SAN LUIS Potosi
Peru	Hospital Nacional Guillermo Almenara Irigoyen	La Victoria, Lima
Peru	Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia	Lima
Peru	Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru	Lima
Poland	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz
Poland	COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny	Gdansk
Poland	MA-LEK Clinical Sp. Z o.o.	Katowice
Poland	Szpital Specjalistyczny im. Rydygiera w Krakowie; Oddzial Neurologii i Udarow Mozgu	Krakow
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.	Lublin
Poland	Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.	Oswiecim
Poland	Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych	Plewiska
Poland	EMC Instytut Medyczny SA	Pozna?
Poland	Wojewódzki Szpital Specjalistyczny Nr 3	Rybnik
Poland	Nmedis sp. z o.o.	Rzeszów
Poland	Osrodek Badan Klinicznych Euromedis	Szczecin
Poland	Centrum Medyczne NeuroProtect	Warszawa
Poland	Instytut Psychiatrii i Neurologii II Klinika Neurologiczna	Warszawa
Portugal	Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)	Braga
Portugal	Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz; Neurologia	Lisboa
Portugal	Hospital Santo Antonio dos Capuchos; Servico de Neurologia	Lisboa
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Russian Federation	Vertebronevrologiya LLC	Kazan	Tatarstan
Russian Federation	Center of Cardiology and Neurology	Kirov
Russian Federation	Regional clinical hospital named after prof. S.V. Ochapovsky	Krasnodar
Russian Federation	FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency	Krasnoyarsk	Krasnojarsk
Russian Federation	Krasnoyarsk State Medical Academy	Krasnoyarsk	Krasnojarsk
Russian Federation	Research Center of Neurology of RAMS	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Hospital #24; Multipal Sclerosis department	Moskva	Moskovskaja Oblast
Russian Federation	Federal center of brain research and neurotechnologies	Moskva	Moskovskaja Oblast
Russian Federation	FSBIH Siberian Regional Medical Centre of FMBA of Russia	Novosibirsk
Russian Federation	Perm SMA n.a. academ. E.A. Vagner	Perm
Russian Federation	National Center of Social Significant Disease	Sankt-peterburg	Leningrad
Russian Federation	N.P. Bechtereva Institute of the Human Brain	Sankt-petersburg	Sankt Petersburg
Russian Federation	Leningrad Regional Clinical Hospital	St Petersburg	Sankt Petersburg
Russian Federation	City Hospital #40 of Kurortniy Administrative District	St. Petersburg	Sankt Petersburg
Russian Federation	Ulyanovsk Regional Clinical Hospital	Ulyanovsk	Uljanovsk
Russian Federation	SHI Sverdlovsk Regional Clinical Hospital #1;Neurology	Yekaterinburg	Sverdlovsk
Spain	Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia	Barcelona
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Neurología	EL Palmar (EL Palmar)	Murcia
Spain	Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología	Madrid
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Switzerland	Inselspital Bern Medizin Neurologie; Neurologische Poliklinik	Bern
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu	Çankaya
Turkey	Haseki Training and Research Hospital; Department of Neurology	Istanbul
Turkey	Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali	Istanbul
Turkey	Sancaktepe Training and Research Hospital; Neurology	Istanbul
Turkey	Selcuk University Medical Faculty; Norology department	Istanbul
Turkey	Erciyes Universitesi; Pediatric Neurology	Kayseri
Turkey	Kocaeli University Hospital; Department of Neurology	Kocaeli
Turkey	Ege Üniversitesi Tip Fakültesi	Lzmir
Turkey	Cumhuriyet Universitesi Tip Fakultesi; Noroloji Bolumu	Merkez
Turkey	Mersin University Medical Faculty; Neurology	Mersin
Turkey	Ondokuz Mayis University School of Medicine; Neurology	Samsun
Ukraine	5th Cherkasy City Center of Primary Health Care	Cherkasy	KIEV Governorate
Ukraine	SI USSRI of Medical and Social Problems of Disabilities of MOHU	Dnipro	KIEV Governorate
Ukraine	Regional Clinical Hospital; Neurology Department	Ivano-Frankivsk
Ukraine	State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine	Kharkiv	Kharkiv Governorate
Ukraine	St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis	Kharkov
Ukraine	Medical Center Dopomoga Plus	Kyiv	Chernihiv Governorate
Ukraine	Medical Center of Private Execution First Private Clinic	Kyiv	KIEV Governorate
Ukraine	Volyn Regional Clinical Hospital	Lutsk
Ukraine	Lvivska oblasna tsentralna likarnia	Lviv	KIEV Governorate
Ukraine	Sumy Regional Clinical Hospital	Sumy	Polissya Okruha
Ukraine	Medical Clinical Research Center of Medical Center LLC Health Clinic	Vinnytsia	Podolia Governorate
Ukraine	Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council	Zaporizhzhia	Katerynoslav Governorate
United Kingdom	Charing Cross Hospital	London
United Kingdom	National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Derriford Hospital	Plymouth
United States	University of Colorado Denver	Aurora	Colorado
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	MS and Neuromuscular Center of Excellence	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Michigan Institute for Neurological Disorders	Farmington Hills	Michigan
United States	Advanced Neurosciences Research LLC	Fort Collins	Colorado
United States	Northwell Health	Great Neck	New York
United States	Alabama Neurology Associates	Homewood	Alabama
United States	University of California Irvine	Irvine	California
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	International Neurorehabilitation Institute	Lutherville	Maryland
United States	Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Advanced Neurosciences Institute	Nashville	Tennessee
United States	Jersey Shore University Medical Centre	Neptune	New Jersey
United States	Lenox Hill Hospital	New York	New York
United States	Baptist Health Lexington	Nicholasville	Kentucky
United States	21st Century Neurology	Phoenix	Arizona
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Neurology Center of San Antonio	San Antonio	Texas
United States	Texas Institute for Neurological Disorders	Sherman	Texas
United States	Stanford University Medical Center; Stanford Neuroscience Health Center	Stanford	California
United States	University of South Florida	Tampa	Florida
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Mexico,  Peru,  Poland,  Portugal,  Russian Federation,  Spain,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to onset of cCDP sustained for at least 12 weeks.	Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT.	Baseline up to approximately 4.3 years
Secondary	Time to onset of cCDP12 independent of protocol-defined relapses (PDR)	Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of protocol defined relapses.	Baseline up to approximately 4.3 years
Secondary	Time to Onset of 12-week CDP (CDP12)	CDP, defined as a sustained increase from baseline in EDSS score of >/=1.0 point in participants with a baseline EDSS score of	Baseline up to approximately 4.3 years
Secondary	Time to >/= 20% Increase in 12-week Confirmed by Timed 25-Foot Walk Test (T25FWT)	The T25FWT is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant is directed to start at one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly and safely as possible.	Baseline up to approximately 4.3 years
Secondary	Change in NfL at Week 96	Biomarker for neurodegeneration NfL	Baseline up Week 96
Secondary	Time to 12-week confirmed 8-point increase in 12-Item Multiple Sclerosis Walking Scale	Self-reported measure of the impact of MS on the individual's ability to walk	Baseline up Week 12
Secondary	Annual Rate of Percent Change from Baseline in Total Brain Volume		Baseline up to approximately 4.3 years
Secondary	Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT)	The SDMT is a performance measure that has demonstrated sensitivity in detecting not only the presence of cognitive impairment but also changes in cognitive functioning over time and in response to treatment. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected orally. A four-point change from baseline is typically considered clinically meaningful.	Baseline up to approximately 4.3 years
Secondary	Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the approved dose ocrelizumab group	Biomarker for neurodegeneration NfL	Baseline up Week 96
Secondary	Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the higher dose ocrelizumab group	Biomarker for neurodegeneration NfL	Baseline up Week 96
Secondary	Time to onset of cCDP24 independent of protocol-defined relapses (PDR)	Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of protocol defined relapses.	Baseline up Week 24
Secondary	Serum Concentration of Ocrelizumab at Specified Timepoints		Weeks 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Secondary	Change in B-cell Levels in Blood		Baseline up to approximately 4.3 years
Secondary	Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood		Baseline up to approximately 4.3 years
Secondary	Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood in Participants with the High versus Low Affinity Fcgamma Receptor 3A (FcgR3A) Genotype per Arm		Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Secondary	Change from Baseline in the Anti-Drug Antibody (ADA) Levels		Week 0, 24, 48, 72, 96, 120
Secondary	Levels of Neurofilament Light Chain (NfL) in Blood		Baseline up to approximately 4.3 years
Secondary	Levels of Interleukin-6 (IL-6) in Blood		Baseline up to approximately 4.3 years
Secondary	Levels of Blood B-cells	Levels of blood B-cells is based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood	Baseline up to approximately 4.3 years
Secondary	Levels of Lymphocytes in Blood		Baseline up to approximately 4.3 years
Secondary	Proportion of Participants with Different DNA Genotypes		Week 0