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

Phase 1

• Conditions: Relapsing Multiple Sclerosis (MS); MedDRA version: 20.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; 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; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-30
• Last Update Posted: 6 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 786

Inclusion Criteria

•Signed ICF
•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 (Thompson et al. 2018)
•EDSS score at screening and baseline, from 3 to 6.5 inclusive
•Score of >= 2.0 on the Functional Systems (FS) scale for the pyramidal system that was due to lower extremity findings
•Patients requiring symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy must be treated at a stable dose during the screening period prior to the initiation of study drug on Day 1 and must have a plan to remain at a stable dose for the duration of study treatment
•Patients must be neurologically stable for at least 30 days prior to randomization and baseline assessments
•Disease duration from the onset of MS symptoms:
Less than 15 years in patients with an EDSS score at screening >5.0
Less than 10 years in patients with an EDSS score at screening >5.0
•Documented evidence of the presence of cerebrospinal fluid-specific oligoclonal bands (established by a historical lumbar puncture or presence at screening in a newly obtained CSF specimen (source documentation of historical laboratory results and method must be verified)
•For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months (as applicable by the ocrelizumab [Ocrevus] local label) after the final dose of ocrelizumab.
•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 (i.e., hysterectomy, complete bilateral oophorectomy).

Are the trial subjects under 18? no
Number of subjects for this age range: 0
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 0

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, including, but not limited to, the following:
History of ischemic cerebrovascular disorders or ischemia of the spinal cord
History or known presence of CNS or spinal cord tumor
History or known presence of potential metabolic causes of myelopathy
History or known presence of infectious causes of myelopathy
History of genetically inherited progressive CNS degenerative disorder
Neuromyelitis optica spectrum disorders
History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease
History or known presence of sarcoidosis
History of severe, clinically significant brain or spinal cord trauma
•Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
•Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study
•History of or currently active primary or secondary immunodeficiency
•Pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of the study drug
Females of childbearing potential must have a negative serum and urine pregnancy test
• 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 (Visit 1) or five half lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
• Previous use of anti-CD20s is allowed if the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy.
• Previous use of mitoxantrone, cladribine, atacicept, and alemtuzumab
• 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 p

Study & Design

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