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

• ClinicalTrials.gov Identifier: NCT05704361
• Recruitment Status: Recruiting
• First Posted: January 30, 2023
• Last Update Posted: April 29, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 4, 2023
• First Posted Date: January 30, 2023
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: August 11, 2021
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2023)

• 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 ]
• Percentage of Participants With Abnormal Laboratory Findings [ Time Frame: Day 1 to Day 169 ]
• Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters [ Time Frame: Day 1 to Day 169 ]
• Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Day 1 to Day 169 ]
  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.

Original Primary Outcome Measures (submitted: January 19, 2023)

• 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 ]
• Percentage of Participants With Abnormal Laboratory Findings [ Time Frame: Day 1 to Day 169 ]
• Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters [ Time Frame: Day 1 to Day 169 ]
• Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Day 1 to Day 169 ]

Current Secondary Outcome Measures (submitted: January 19, 2023)

• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• Cerebrospinal Fluid (CSF) Concentration of RO7121932 (Cohorts 5 and 6, and later cohorts, as appropriate) [ Time Frame: Day 1 to Day 169 ]
• Percentage of Participants With Anti-RO7121932 Antibodies [ Time Frame: Predose on Day 1, and on Days 8, 22, 29, 57, 85, 169 ]
• Time Course of B cells in Blood and CSF [ Time Frame: Day 1 to Day 169 ]
• Change From Baseline in B-cell count in Blood and CSF [ Time Frame: Day 1 to Day 169 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

Drug: RO7121932

Participants will receive a single dose of RO7121932 administered as IV infusion.

Study Arms

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.

Intervention: Drug: RO7121932

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 19, 2023): 63
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2025
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Belgium, Canada, Germany, Israel, Italy, Moldova, Republic of, Poland, Portugal, Romania, United States

Administrative Information

• NCT Number: NCT05704361
• Other Study ID Numbers: BP42230; 2020-004122-33 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2024