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

NCT05704361 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: BP422302020-004122-332023-509357-31-00
• Study Type: interventional
• Target: 129
• Locations: 12 countries
• Sites: 32

Brief 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).

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (4)

• Parts 1, 2, and 3: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) With Severity of AEs Measured According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE V5)

  Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3

• Parts 1, 2, and 3: Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)

  The C-SSRS is an interview-based instrument used to assess baseline incidence of suicidal ideation (SI) and behavior. The assessment includes "yes" or "no" responses for 5 questions, each related to SI (wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent, active SI with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation (if present), from 0 to 5. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates SI or behavior, with 5 being the most severe.

  Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3

• Parts 2 and 3: Percentage of Participants With Local Pain at the Site of Injection Assessed Using the Visual Analog Scale (VAS)

  VAS is a 100 millimetre (mm) horizontal visual analog scale with values 0 to 100 mm to indicate pain. The following cutpoints on the VAS will be considered in the interpretation of the pain data: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). A higher score indicates greater pain intensity.

  Day 1, 2, 5, 8 for Part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for Part 3

• Parts 2 and 3: Percentage of Participants With Local Injection-site Reaction Using Local Injection-site Symptom Assessment (LISSA)

  LISSA form will be used to assess the participant's injection site for the following categories of reactions: Burning, Itching, Bruising, Erythema (redness), Hive formation, Induration, Swelling, Ecchymosis, Sensitivity, Papules, Stinging, Blister, Cold sensation, and Other. These reactions will be described using the following scale: Unable to assess, less than a dime (\<18 mm/\<0.7 inches), a dime (18 mm/0.7 inches), a nickel (21 mm/0.8 inches), a quarter (24 mm/1 inch), a half dollar (31 mm/1.2 inches), larger than a half dollar (\>31 mm/\>1.2 inches). A higher score indicates high injection site reactions.

  Day 1,2, 5, 8 for Part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for Part 3

Secondary Outcomes (17)

• Parts 1, 2 and 3 (Week 1 and Week 4): Time to Maximum Observed Concentration (Tmax) of RO7121932

  Day 1 to Day 169 for Part 1 and Part 2; Days 1, 2, 5 and, 22 for Part 3

• Parts 1, 2 and 3 (Week 1 and Week 4): Maximum Observed Serum Concentration (Cmax) of RO7121932

  Day 1 to Day 169 for Part 1 and Part 2; Days 1, 2, 5 and, 22 for Part 3

• Parts 1, 2 and 3 (Week 1 and Week 4): Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose

  Day 1 (predose) to Day 8 (168 hours post-dose) for Parts 1, 2, and 3 (Week 1) and Day 22 (predose) to Day 29 (168 hours post-dose) for Part 3 (Week 4)

• Parts 1 and 2: Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast)

  Day 1 to Day 169 for Part 1 and Part 2

• Parts 1 and 2: AUC From Time 0 to Infinity (AUCinf)

  Day 1 to Day 169 for Part 1 and Part 2

Study Arms (3)

Part 1: Single Ascending Dose (SAD) IV: RO7121932- Dose Escalation Cohorts 1 to 6 and Later Cohorts

EXPERIMENTAL

Participants will receive a single IV dose of RO7121932 on treatment Day 1. The planned starting dose of RO7121932 is 7 milligrams (mg) and will be escalated up to 2000 mg. The maximum dose will not exceed 4000 mg . Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Drug: RO7121932 IV

Part 2: SAD SC: RO7121932- Dose Escalation Cohorts 1 to 2

EXPERIMENTAL

Participants will receive a single SC dose of RO7121932 on treatment Day 1. The planned starting dose of RO7121932 is 70 mg and will be escalated up to 200 mg. Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Drug: RO7121932 SC

Part 3: Multiple Ascending Dose (MAD) SC: RO7121932- Dose Escalation Cohorts 1 to 3

EXPERIMENTAL

Participants will receive multiple SC doses of RO7121932, once weekly on treatment Day 1 through Day 22. The planned starting dose of RO7121932 is 70 mg and will be escalated up to 700 mg. Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Drug: RO7121932 SC

Interventions

RO7121932 IV DRUG

Participants will receive RO7121932, as an IV infusion, per the schedule specified in the treatment arms.

Part 1: Single Ascending Dose (SAD) IV: RO7121932- Dose Escalation Cohorts 1 to 6 and Later Cohorts

RO7121932 SC DRUG

Participants will receive RO7121932, as SC injection, per the schedule specified in the treatment arms.

Part 2: SAD SC: RO7121932- Dose Escalation Cohorts 1 to 2; Part 3: Multiple Ascending Dose (MAD) SC: RO7121932- Dose Escalation Cohorts 1 to 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (32)

Stanford University Medical Center

Stanford, California, 94305, United States

COMPLETED

Yale University Multiple Sclerosis Center

New Haven, Connecticut, 06473, United States

COMPLETED

University of South Florida

Tampa, Florida, 33612, United States

WITHDRAWN

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

WITHDRAWN

UC Health, LLC.

Cincinnati, Ohio, 45267, United States

WITHDRAWN

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

RECRUITING

Universitätsklinikum "Carl Gustav Carus"

Dresden, 01307, Germany

ACTIVE NOT RECRUITING

Universitätsmedizin Göttingen Georg-August-Universität

Göttingen, 37075, Germany

COMPLETED

Klinikum rechts der Isar der TU Muenchen

München, 81675, Germany

COMPLETED

Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie

Münster, 48149, Germany

RECRUITING

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, 72076, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

WITHDRAWN

IRCCS Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

RECRUITING

Fond. Istituto Neurologico C.Besta

Milan, Lombardy, 20133, Italy

RECRUITING

ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical Hospital

Chisinau, MD-2025, Moldova

COMPLETED

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

WITHDRAWN

Regionalny Szpital Specjalistyczny im. W. Bieganskiego

Grudzi?dz, 86-300, Poland

COMPLETED

MedPolonia

Poznan, 60-693, Poland

RECRUITING

Osrodek Badan Klinicznych Euromedis

Szczecin, 70-111, Poland

RECRUITING

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, 02-957, Poland

WITHDRAWN

SPSK nr 1

Zabrze, 41-800, Poland

COMPLETED

Hospital de Braga

Braga, 4710-243, Portugal

RECRUITING

Hospital Santo Antonio dos Capuchos

Lisbon, 1169-050, Portugal

RECRUITING

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

Santa Maria da Feira, 4520-211, Portugal

RECRUITING

ARENSIA Exploratory Medicine SRL - Bucharest (Monza Medical Center)

Bucharest, 011658, Romania

RECRUITING

ARENSIA Exploratory Medicine, County Emergency Hospital

Cluj-Napoca, 40006, Romania

RECRUITING

University Clinical Center of Serbia

Belgrade, 11000, Serbia

RECRUITING

Hospital Universitari Vall dHebron (CEMCAT)

Barcelona, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: BP42230 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 30, 2023
• Study Start: August 11, 2021
• Primary Completion (Estimated): July 8, 2027
• Study Completion (Estimated): July 8, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (6); SE (1); MO (1); PL (6); BE (2); ES (1); IT (2); PT (3); US (5); CA (1); RO (2); IL (2)