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History of Changes for Study: NCT05704361
A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous RO7121932 in Participants With Multiple Sclerosis
Latest version (submitted April 26, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 19, 2023 None (earliest Version on record)
2 February 3, 2023 Contacts/Locations, Study Status and Outcome Measures
3 March 3, 2023 Study Status and Contacts/Locations
4 April 27, 2023 Study Status and Contacts/Locations
5 May 9, 2023 Study Status and Contacts/Locations
6 May 13, 2023 Eligibility and Study Status
7 May 18, 2023 Study Status and Study Identification
8 June 16, 2023 Contacts/Locations and Study Status
9 July 14, 2023 Study Status and Contacts/Locations
10 August 11, 2023 Study Status and Contacts/Locations
11 September 11, 2023 Study Status and Contacts/Locations
12 October 11, 2023 Study Status and Contacts/Locations
13 November 10, 2023 Study Status and Contacts/Locations
14 December 8, 2023 Study Status and Contacts/Locations
15 January 4, 2024 Study Status and Contacts/Locations
16 February 2, 2024 Study Status and Contacts/Locations
17 February 6, 2024 Contacts/Locations and Study Status
18 March 1, 2024 Study Status and Contacts/Locations
19 March 28, 2024 Contacts/Locations and Study Status
20 April 26, 2024 Study Status and Contacts/Locations
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Study NCT05704361
Submitted Date:  January 19, 2023 (v1)

Open or close this module Study Identification
Unique Protocol ID: BP42230
Brief Title: A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous RO7121932 in Participants With Multiple Sclerosis
Official Title: 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
Secondary IDs: 2020-004122-33 [EudraCT Number]
Open or close this module Study Status
Record Verification: January 2023
Overall Status: Recruiting
Study Start: August 11, 2021
Primary Completion: January 31, 2025 [Anticipated]
Study Completion: January 31, 2025 [Anticipated]
First Submitted: January 4, 2023
First Submitted that
Met QC Criteria:
January 19, 2023
First Posted: January 30, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:
January 19, 2023
Last Update Posted: January 30, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: 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)
Detailed Description:
Open or close this module Conditions
Conditions: Multiple Sclerosis
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 63 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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)
[ Time Frame: Day 1 to Day 169 ]

2. Percentage of Participants With Abnormal Laboratory Findings
[ Time Frame: Day 1 to Day 169 ]

3. Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters
[ Time Frame: Day 1 to Day 169 ]

4. Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
[ Time Frame: Day 1 to Day 169 ]

Secondary Outcome Measures:
1. Time to Maximum Observed Concentration (Tmax) of RO7121932
[ Time Frame: 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 ]

2. Maximum Observed Serum Concentration (Cmax) of RO7121932
[ Time Frame: 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 ]

3. Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose
[ Time Frame: 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 ]

4. Area Under the Serum Concentration-Time Curve up to the Last Measurable Concentration (AUClast)
[ Time Frame: 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 ]

5. AUC From Time 0 to Infinity (AUCinf)
[ Time Frame: 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 ]

6. Total Body Clearance (CL) Of RO7121932
[ Time Frame: 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 ]

7. Terminal Rate Constant of RO7121932
[ Time Frame: 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 ]

8. Apparent Terminal Half-Life (T1/2) of RO7121932
[ Time Frame: 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 ]

9. Cerebrospinal Fluid (CSF) Concentration of RO7121932 (Cohorts 5 and 6, and later cohorts, as appropriate)
[ Time Frame: Day 1 to Day 169 ]

10. Percentage of Participants With Anti-RO7121932 Antibodies
[ Time Frame: Predose on Day 1, and on Days 8, 22, 29, 57, 85, 169 ]

11. Time Course of B cells in Blood and CSF
[ Time Frame: Day 1 to Day 169 ]

12. Change From Baseline in B-cell count in Blood and CSF
[ Time Frame: Day 1 to Day 169 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening
  • Non-active participants with relapsing MS or progressive MS who fulfilled international panel criteria for diagnosis, as per the revised McDonald 2017 criteria (Thompson 2018) and the Lublin criteria (Lublin et al. 2014; Lublin et al 2020) (see also exclusion criterion 1)
  • 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:

  • Any signs of disease activity suggested clinically (relapse) or by magnetic resonance imaging (MRI) (gadolinium [Gd]-enhancing T1 lesions or new or enlarging T2 lesions) within 12 months prior to Screening
  • 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 the 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 Screening but should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial
  • Previous treatment with alemtuzumab, daclizumab, cladribine, mitoxantrone, cyclophosphamide, total body irradiation, bone marrow transplantation, and hematopoietic stem cell transplantation.
  • Previous treatment with anti-CD20 B-cell-depleting therapies (e.g., rituximab, ocrelizumab, or ofatumumab)
    1. <12 months prior to Screening,
    2. ≥12 months prior to Screening, if B-cells are outside the normal range, or not back to individual baseline ± 20% (if data are available),
    3. 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 Screening).

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
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: BP42230 https://forpatients.roche.com/
Telephone: 888-662-6728 (U.S. Only)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, California
Stanford University Medical Center; Stanford Neuroscience Health Center
[Recruiting]
Stanford, California, United States, 94305
United States, Connecticut
Yale University Multiple Sclerosis Center
[Recruiting]
New Haven, Connecticut, United States, 06473
United States, Florida
University of South Florida
[Recruiting]
Tampa, Florida, United States, 33612
United States, Massachusetts
University of Massachusetts Medical School
[Recruiting]
Worcester, Massachusetts, United States, 01655
United States, Ohio
UC Health, LLC.
[Recruiting]
Cincinnati, Ohio, United States, 45219
Belgium
UZ Gent
[Recruiting]
Gent, Belgium, 9000
Germany
Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden
[Recruiting]
Dresden, Germany, 01307
Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Neurologie
[Recruiting]
Göttingen, Germany, 37075
Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
[Recruiting]
München, Germany, 81675
Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie
[Recruiting]
Münster, Germany, 48149
Israel
Hadassah University Hospital - Ein Kerem
[Recruiting]
Jerusalem, Israel, 9112001
Tel Aviv Sourasky Medical Center; Department of Neurology
[Withdrawn]
Tel Aviv, Israel, 6423906
Italy, Lombardia
IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
[Recruiting]
Milano, Lombardia, Italy, 20132
Poland
Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
[Recruiting]
Gdańsk, Poland, 80-214
Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Neurologiczny
[Recruiting]
Grudziądz, Poland, 86-300
Osrodek Badan Klinicznych Euromedis
[Recruiting]
Szczecin, Poland, 70-111
Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
[Recruiting]
Warszawa, Poland, 02-957
Portugal
Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
[Recruiting]
Braga, Portugal, 4710-243
Open or close this module IPDSharing
Plan to Share IPD: Yes
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).
Supporting Information:
Time Frame:
Access Criteria:
URL:
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Citations:
Links:
Available IPD/Information:

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