Multiple sclerosis, brain shuttle Nervous System Diseases Multiple sclerosis
Conditions
Interventions
All participants in this study will receive a single dose of RO7121932 in the morning of day 1, which is given by an intravenous infusion (via a tube linked to a small needle into the vein).
Six dose
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 16/05/2022: 1. Ability to provide, informed consent, to be able to follow the SoA and to comply with the study protocol according to the International Council on Harmonisation and local regulations 2. 18 to 65 years, inclusive, at time of signing Informed Consent Form 3. Fluent in the language of the Investigator and study staff, and able to communicate with the study staff 4. Expanded Disability Status Scale (EDSS) score =7.0 at Screening 5. Non-active patients 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) 6. Patients not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up) 7. Female participants must practice abstinence or otherwise use contraception Previous inclusion criteria: 1. Ability to provide written, informed consent, to be able to follow the SoA and to comply with the study protocol according to the International Council on Harmonisation and local regulations 2. 18 to 55 years, inclusive, at time of signing Informed Consent Form 3. Fluent in the language of the Investigator and study staff, and able to communicate with the study staff 4. Expanded Disability Status Scale (EDSS) score =6.0 at Screening 5. Non-active patients with relapsing MS (RMS) or progressive MS (PMS) who fulfilled international panel criteria for diagnosis, as per the revised McDonald 2017 criteria (Thompson 2018) and the Lublin criteria (Lublin et al. 2014) (see also exclusion criteria 1 and 2) 6. Patients not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up) 7. Male and female participants must practice abstinence or otherwise use contraception
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 16/05/2022: 1. 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 2. Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML 3. 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 4. 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 Note: Participants who tested positive for SARS-CoV-2 in the past but are without any current symptoms related to coronavirus disease 2019 should be carefully and comprehensively evaluated as per usual medical practice and institutional guidance before enrollment. The Investigator should assess the benefit/risk ratio for each participant with a history of SARS-CoV2 infection; enrollment has to be discussed with both the participant and the Sponsor. For participants not yet fully immunized against SARS-CoV-2, COVID-19 testing should be performed up to 48 hours prior to study drug administration, per local institutional guidelines, if required per local regulations. 5. Participants with a current diagnosis of epilepsy 6. Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases that in the Investigator's judgment may affect the interpretation of study results or patient safety 7. 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. 8. Any concomitant disease that may require treatment with systemic corticosteroids or immunosuppressants during the course of the study 9. History of currently active primary or secondary (non-drug-related) immunodeficiency 10. History of hypersensitivity to biologic agents or any of the excipients in the formulation. 11. 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 (skin infection, develop abnormalities in lower spine, etc) which could prevent the lumbar puncture procedure Prior/Concomitant Therapy: 12. 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. Justification for withdrawal from medication must be documented. 13. Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicabl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 of abnormal vital signs and electrocardiogram (ECG) parameters: blood pressure and pulse rate measured by an automated device and ECG abnormalities measured by 12-lead ECG from baseline to day 169/early termination 4. Suicidal risk monitoring measured using the Columbia-Suicide Severity Rating Scale at baseline, day 3, day 8, day 29, day 85 and day 169/early termination | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Serum PK parameters of RO7121932 measured by specific and validated methods on serum samples taken at predose, 0.5, 1 (or end of infusion), 2, 3 (or end of infusion), 8 h on day 1, on day 2, day 3, day 5, day 8, day 15, day 22, day 29, day 57, day 85, day 113, and day 169/early termination 2. CSF concentration of RO7121932 (Cohort 5 and 6 only) measured by specific and validated methods on 1 CSF sample taken between day -7 and day -1, prior to dosing and a postdose CSF sample taken anytime from day 2 to day 169. A third optional CSF sample (if consented) is also taken from day 2 to day 169 3. Incidence of anti-RO7121932 antibodies measured using validated screening, confirmatory, and titer assays on serum samples taken at predose, day 8, day 22, day 29, day 57, day 85 and day 169/early termination 4. PD parameters: 4.1. B cells measured by flow cytometry from blood samples taken at screening, predose on day 1, day 2, day 8, day 22, day 57, day 85 and day 169/early termination 4.2. B cells (Cohort 5 and 6 only) measured by flow cytometry from 1 CSF sample taken between day -7 and day -1, prior to dosing and a postdose CSF sample taken anytime from day 2 to day 169. A third optional CSF sample (if consented) is also taken from day 2 to day 169 | — |
Countries
Belgium, Germany, Israel, Italy, Poland, Portugal, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed