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: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-29
• 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 at least one of cerebrospinal fluidspecific
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