A Study to Investigate the Safety, Tolerability, and Processing by the

A Multiple-center, Non-randomized, Open-label, Adaptive, Single-ascending Dose (Part 1 and Part 2) and Multiple-ascending Dose (Part 3), and Long-term Safety (Part 4), Parallel, Phase IB Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of RO7121932 Following Intravenous (Parts 1 and 4) and Subcutaneous (Parts 2, 3 and 4) Administration in Participants With Multiple Sclerosis

Running, not recruitingPhase 1Relapsing and progressiveNCT057043612023-509357-31-00ISRCTN16295177

What it found

Still running

No result yet.

What was tested

Treatment tested

  • RO7121932 IV
  • RO7121932 SC
  • RO7121932

What it measured

Main measures

  • Parts 1, 2, 3, and 4: 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; Day 1 to Day 253 for Part 4

    Safety

  • Parts 1, 2, 3, and 4: Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)

    Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3; Day 1 to Day 253 for Part 4

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

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

    Pain

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

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

    Safety

  • Part 4: Percentage of Participants With Local Injection-site Reactions

    Day 1 to Day 253

    Safety

  • 1. Incidence, severity, seriousness, and causal relationship of adverse events (AEs): AEs taken from participant's medical records throughout the course of the study (baseline to day 169/early termination) 2. Incidence of abnormal laboratory findings: clinical laboratory safety assessments measured by the evaluation of blood and urine tests from baseline to day 169/early termination 3. Incidence o

    Safety

Other measures (19)

  • 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

    How the body handles the medicine

  • 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)

    How the body handles the medicine

  • 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

    How the body handles the medicine

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

    Day 1 to Day 169 for Part 1 and Part 2

    How the body handles the medicine

  • Part 1: Total Body Clearance (CL) Of RO7121932

    Day 1 to Day 169

    How the body handles the medicine

  • Parts 2 and 3 (Week 4): Apparent Clearance (CL/F) of RO7121932

    Day 1 to Day 169 for Part 2; Day 22 to Day 29 for Part 3

    How the body handles the medicine

  • Parts 1, 2 and 3: Terminal Rate Constant of RO7121932

    Day 1 to Day 169 for Part 1 and Part 2; Day 22 to Day 197 for Part 3

  • Parts 1, 2 and 3: Apparent Terminal Half-Life (T1/2) of RO7121932

    Day 1 to Day 169 for Part 1 and Part 2; Day 22 to Day 197 for Part 3

    MRI lesionsHow the body handles the medicine

  • Part 3: Trough Concentrations (Ctrough) of RO7121932

    Day 1 to Day 197

    How the body handles the medicine

Who could take part

Relapsing and progressive · 18 to 65

Show the full criteria

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) * Biological male and female participants * 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 brain 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, gastrointestinal 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 * History of inflammatory bowel disease or other clinically significant gastrointestinal disorders * 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-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

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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), and multiple-ascending SC doses following a single IV dose (Part 4) of RO7121932 in participants with multiple sclerosis (MS). Only Parts 1 and 2 of the study will be conducted in the United States, whereas Parts 1, 2, 3, and 4 will be conducted in all other participating countries outside the United States.

Papers

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    History

      1. Started

        Aug 2021

      2. Main results due

        Jul 2027

      3. Finished

        Jul 2027

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