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

A Multiple-center, Non-randomized, Open-label, Adaptive, Single Ascending Dose, Phase I Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of RO7121932 Following Intravenous Administration in Patients With Multiple Sclerosis

The primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) doses of RO7121932 in participants with multiple sclerosis (MS)

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: RO7121932

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP42230 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Active, not recruiting
    • UZ Gent
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Recruiting
      • Montreal Neurological Institute and Hospital; Pharmacy Department
• Germany
  • Dresden, Germany, 01307
    • Active, not recruiting
    • Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden
  • Göttingen, Germany, 37075
    • Recruiting
    • Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Neurologie
  • München, Germany, 81675
    • Recruiting
    • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie
• Israel
  • Jerusalem, Israel, 9112001
    • Active, not recruiting
    • Hadassah University Hospital - Ein Kerem
  • Tel Aviv, Israel, 6423906
    • Withdrawn
    • Tel Aviv Sourasky Medical Center; Department of Neurology
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Recruiting
      • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Milano, Lombardia, Italy, 20133
      • Recruiting
      • Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Recruiting
    • ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical Hospital
• Poland
  • Gda?sk, Poland, 80-214
    • Active, not recruiting
    • Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
  • Grudzi?dz, Poland, 86-300
    • Completed
    • Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Neurologiczny
  • Poznan, Poland, 60-693
    • Recruiting
    • MedPolonia
  • Szczecin, Poland, 70-111
    • Recruiting
    • Osrodek Badan Klinicznych Euromedis
  • Warszawa, Poland, 02-957
    • Withdrawn
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
  • Zabrze, Poland, 41-800
    • Recruiting
    • SPSK nr 1; Klinika Neurologii
• Portugal
  • Braga, Portugal, 4710-243
    • Active, not recruiting
    • Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
• Romania
  • Cluj-Napoca, Romania, 400006
    • Active, not recruiting
    • ARENSIA Exploratory Medicine, County Emergency Hospital
• United States
  • California
    • Stanford, California, United States, 94305
      • Active, not recruiting
      • Stanford University Medical Center; Stanford Neuroscience Health Center
  • Connecticut
    • New Haven, Connecticut, United States, 06473
      • Recruiting
      • Yale University Multiple Sclerosis Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Withdrawn
      • University of South Florida
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts Medical School
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • UC Health, LLC.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening
• Participants with RMS or 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 recent clinical disease activity
• Evidence of recent MRI activity
• 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
• Cohorts 5 and 6 and later cohorts, as appropriate: 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 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-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 PD or 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 suicidal ideation 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7121932: Dose Escalation Cohorts 1 to 6; 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; Participants will receive a single dose of RO7121932 administered as IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 v 5)		Day 1 to Day 169
Percentage of Participants With Abnormal Laboratory Findings		Day 1 to Day 169
Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters		Day 1 to Day 169
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 and behavior. The assessment includes "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation 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 suicidal ideation or behavior, with 5 being the most severe.	Day 1 to Day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Maximum Observed Concentration (Tmax) of RO7121932	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Maximum Observed Serum Concentration (Cmax) of RO7121932	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Area Under the Serum Concentration-Time Curve up to the Last Measurable Concentration (AUClast)	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
AUC From Time 0 to Infinity (AUCinf)	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Total Body Clearance (CL) Of RO7121932	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Terminal Rate Constant of RO7121932	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Apparent Terminal Half-Life (T1/2) of RO7121932	Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Cerebrospinal Fluid (CSF) Concentration of RO7121932 (Cohorts 5 and 6, and later cohorts, as appropriate)	Day 1 to Day 169
Percentage of Participants With Anti-RO7121932 Antibodies	Predose on Day 1, and on Days 8, 22, 29, 57, 85, 169
Time Course of B cells in Blood and CSF	Day 1 to Day 169
Change From Baseline in B-cell count in Blood and CSF	Day 1 to Day 169

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: BP42230; 2020-004122-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No