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

Roche

Status and phase: Enrolling; Phase 1

Conditions: Multiple Sclerosis

Treatments: Drug: RO7121932 - MAD; Drug: RO7121932 SC - SAD; Drug: RO7121932 IV - SAD

Study type: Interventional

Funder types: Industry

Identifiers

NCT05704361

BP42230

2020-004122-33 (EudraCT Number)

Details and patient eligibility

About

The primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) (Part 1) and subcutaneous (SC) (Part 2) doses of RO7121932 and multiple ascending SC (Part 3) doses of RO7121932 in participants with multiple sclerosis (MS).

Enrollment: 129 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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)
• 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 magnetic resonance imaging (MRI) activity as defined by the presence of ≥ 1 Gadolinium-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
• 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
• 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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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129 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: RO7121932 IV - SAD

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

Experimental group

Description:

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.

Treatment:

Drug: RO7121932 SC - SAD

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

Experimental group

Description:

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.

Treatment:

Drug: RO7121932 - MAD