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NCT05704361PHASE1Recruiting

A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous and Subcutaneous RO7121932 Administration in Participants With Multiple Sclerosis

Hoffmann-La Roche

Start Date

8/11/2021

Completion Date

7/8/2027

Summary

The primary purpose of the study is to evaluate the safety and tolerability of a single-ascending intravenous (IV) dose (Part 1), a single-ascending subcutaneous (SC) dose (Part 2), and multiple ascending SC doses (Part 3) of RO7121932 in participants with multiple sclerosis (MS).

Eligibility Criteria

Age Range: 18 years to 65 years

Inclusion Criteria: * Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening * Participants with relapsing multiple sclerosis (RMS) or progressive multiple sclerosis (PMS) who fulfil international panel criteria for diagnosis (McDonald 2017 criteria) * Participants not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up) * Female participants must practice abstinence or otherwise use contraception Exclusion Criteria: * Evidence of clinical disease activity as defined by any clinical relapse within 3 months prior to screening, or by \>1 clinical relapse within 12 months prior to screening * Evidence of magnetic resonance imaging (MRI) activity as defined by the presence of ≥ 1 Gadolinium (Gd)-enhancing T1 lesion in the screening MRI scan or by ≥ 4 new or enlarging T2 lesions in the screening scan as compared to a reference scan * Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML * Known presence of other neurological disorders that may mimic MS including but not limited to: neuromyelitis optica spectrum disease, Lyme disease, untreated Vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, and untreated hypothyroidism * Known active or uncontrolled bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds, including participants exhibiting symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6 weeks prior to Day 1 * Participants with a current diagnosis of epilepsy * Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases * History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening. Basal or squamous cell carcinoma of the skin that has been excised and is considered cured and in situ carcinoma of the cervix treated with apparent success by curative therapy \>1 year prior to screening is not exclusionary * Any concomitant disease that may require treatment with systemic corticosteroids or immunosuppressants during course of the study * History of currently active primary or secondary (non-drug-related) immunodeficiency * History of hypersensitivity to biologic agents or any of the excipients in the formulation * Only for cohorts where CSF samples are planned to be collected: Participants with a history of spinal cord compression, raised intra-cerebral pressure, clinically significant vertebral joint pathology or any other current abnormalities in the lumbar region which could prevent the lumbar puncture procedure. Prior/Concomitant Therapy: * Treatment with any approved MS treatment at Screening. Participants may become eligible after completion of a washout period prior to acquiring any screening laboratory tests but should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial * Previous treatment with RO7121932, alemtuzumab, cladribine, mitoxantrone, cyclophosphamide, total body irradiation, bone marrow transplantation, and hematopoietic stem cell transplantation. For the USA only, previous treatment with daclizumab * Previous treatment with anti-cluster of differentiation 20 (CD20) B-cell-depleting therapies (e.g., rituximab, ocrelizumab, or ofatumumab) * \<12 months prior to acquiring any screening laboratory tests, * ≥12 months prior to acquiring any screening laboratory tests, if B-cells are outside the normal range, or not back to individual baseline ± 20% (if data are available), * If discontinuation of a prior B-cell depletion therapy was motivated by safety reasons * Current or prior treatment with natalizumab (if \<24 months prior to acquiring any screening laboratory tests) Prior/Concurrent Clinical Study Experience: \- Participation in an investigational drug medicinal product or medical device study within 30 days before Screening or within five times the pharmacodynamic (PD) or pharmacokinetic (PK) half-life (if known), whichever is longer Diagnostic Assessments: * Positive result on human immunodeficiency virus (HIV1) and HIV2, hepatitis C, or hepatitis B * Participants with SI or behavior within 6 months prior to Screening or participants who, in the Investigator's judgment, pose a suicidal or homicidal risk * Vaccination with a live or live-attenuated vaccine within 6 weeks prior to Day 1

Interventions

DRUG

RO7121932 IV

DRUG

RO7121932 SC

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Conditions

Multiple Sclerosis

Locations

Stanford University Medical Center

Stanford, California 94305

United States

Yale University Multiple Sclerosis Center

New Haven, Connecticut 06473

United States

University of South Florida

Tampa, Florida 33612

United States

University of Massachusetts Medical School

Worcester, Massachusetts 01655

United States

UC Health, LLC.

Cincinnati, Ohio 45267

United States

Cliniques Universitaires St-Luc

Brussels, 1200

Belgium

UZ Gent

Ghent, 9000

Belgium

Montreal Neurological Institute and Hospital

Montreal, Quebec H3A 2B4

Canada

Universitätsklinikum "Carl Gustav Carus"

Dresden, 01307

Germany

Universitätsmedizin Göttingen Georg-August-Universität

Göttingen, 37075

Germany

Klinikum rechts der Isar der TU Muenchen

München, 81675

Germany

Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie

Münster, 48149

Germany

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, 72076

Germany

Universitätsklinikum Ulm

Ulm, 89081

Germany

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

IRCCS Ospedale San Raffaele

Milan, Lombardy 20132

Italy

Fond. Istituto Neurologico C.Besta

Milan, Lombardy 20133

Italy

ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical Hospital

Chisinau, MD-2025

Moldova

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214

Poland

Regionalny Szpital Specjalistyczny im. W. Bieganskiego

Grudzi?dz, 86-300

Poland

MedPolonia

Poznan, 60-693

Poland

Osrodek Badan Klinicznych Euromedis

Szczecin, 70-111

Poland

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, 02-957

Poland

SPSK nr 1

Zabrze, 41-800

Poland

Hospital de Braga

Braga, 4710-243

Portugal

Hospital Santo Antonio dos Capuchos

Lisbon, 1169-050

Portugal

Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião

Santa Maria da Feira, 4520-211

Portugal

ARENSIA Exploratory Medicine SRL - Bucharest (Monza Medical Center)

Bucharest, 011658

Romania

ARENSIA Exploratory Medicine, County Emergency Hospital

Cluj-Napoca, 40006

Romania

University Clinical Center of Serbia

Belgrade, 11000

Serbia

Hospital Universitari Vall dHebron (CEMCAT)

Barcelona, 08035

Spain