A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults with Primary Progressive Multiple Sclerosis

Phase 1

• Conditions: Primary Progressive Multiple Sclerosis (MS); MedDRA version: 20.1Level: LLTClassification code 10039720Term: Sclerosis multipleSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-000894-26-HU
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-06
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 699

Inclusion Criteria

? Ages 18-55 years at time of screening
? Ability to comply with the study protocol
? Diagnosis of PPMS in accordance with the revised McDonald Criteria 2017
? Expanded disability status scale (EDSS) score at screening and baseline >=3- 6.5, inclusive
? Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
? Average 9HPT score over four trials (two trials with each hand) at screening and over four trials at baseline (two trials with each hand) respectively, up to 250 (inclusive) seconds
? Score of >=2.0 on the Functional Systems (FS) scale for the pyramidal system that was due to lower extremity findings at screening and baseline
? Documented MRI of brain with abnormalities consistent with MS
? Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
? Patients must be neurologically stable for at least 30 days prior to randomization and baseline assessments
? Disease duration from the onset of MS symptoms: 1] If EDSS score at screening is <=5.0, disease duration from the onset of MS symptoms must be less than 10 years , 2] If EDSS score at screening is >5.0, disease duration from the onset of MS symptoms must be less than 15 years Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands
? For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive method
? For female patients without reproductive potential: Females may be enrolled if post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 699
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

? History of relapsing remitting or secondary progressive MS at screening
? Any known or suspected active infection at screening or baseline, or any major episode of infection requiring hospitalization or treatment with IV anti microbials within 8 weeks prior to and during screening or treatment with oral anti microbials within 2 weeks prior to and during screening
? History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
? History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
? Immunocompromised state
? Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
? Inability to complete an MRI or contraindication to gadolinium administration
? Contraindications to mandatory pre medications for IRRs
? Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
? Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
? Significant, uncontrolled disease, that may preclude patient from participating in the study
? History of or currently active primary or secondary (non-drug related) immunodeficiency
? Pregnant or breastfeeding or intending to become pregnant during the study
? Lack of peripheral venous access
? History of alcohol or other drug abuse within 12 months prior to screening
? Treatment with any investigational agent within 24 weeks prior to screening or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedure for MS Previous use of anti-CD20s (including ocrelizumab), unless the last infusion was more than 2 years before screening, or if B-cell count is normal, and if the stop of the treatment was not motivated by safety reasons or lack of efficacy
? Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab and daclizumab
? Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
? Previous treatment with natalizumab within 4.5 months of baseline
? Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
? Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication. The PD effects of the previous medication must also be considered when determining the required time for washout.
? Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
? Any previous history of transplantation or anti-rejection therapy
? Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
? Systemic corticosteroid therapy within 4 weeks prior to screening
? Positive screening tests for active, latent, or inadequately treated hepatitis B
? Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
? Any additional exclusionary criterion as per ocrelizumab (Ocrevus) local label, if more stringent than the above

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified