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

Study Purpose

This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and pharmacokinetics of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks in participants with PPMS, in comparison to the approved 600 mg dose of ocrelizumab.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 55 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Diagnosis of primary progressive multiple sclerosis (PPMS).

- Expanded disability status scale (EDSS) score at screening and baseline, from 3 to 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 (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds.

- Score of >/= to 2.0 on the Functional Systems 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.

- Participants must be neurologically stable for at least 30 days prior to randomization and baseline.

- Disease duration from the onset of MS symptoms; if EDSS score at screening is less or equal to 5, disease duration must be less than 10 years; If EDSS score at screening is more than 5, disease duration 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 methods.

- For female participants without reproductive potential, may be enrolled if post-menopausal unless receiving a hormonal therapy for her menopause or if surgically sterile.

Exclusion Criteria:

- History of relapsing remitting or secondary progressive MS at screening.

- Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening.

- History of confirmed or suspected progressive multifocal leukoencephalopathy.

- 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 participant 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.

- Lack of peripheral venous access.

- History of alcohol or other drug abuse within 12 months prior to screening.

- Treatment with any investigational agent 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, B-cell count is normal, and 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.

- Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation.

- Any previous history of transplantation or anti-rejection therapy.

- Treatment with intravenous (IV) immunoglobulin (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 local label, if more stringent than the above.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04548999
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hoffmann-La Roche
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Clinical Trials
Principal Investigator Affiliation	Hoffmann-La Roche
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Mexico, Peru, Poland, Portugal, Puerto Rico, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Multiple Sclerosis

Additional Details

Participants will be treated for a minimum of 120 weeks in the double-blind phase. Upon positive primary results after the double-blind phase, an optional higher dose extension treatment (OLE phase) is planned for eligible participants. The OLE will be carried out for approximately 96 weeks. Participants will be followed for safety for 48 weeks thereafter. Participants whose B-cell levels still did not replete to their baseline level or the lower limit of normal (LLN), whichever is lower, will move into the B-cell monitoring (BCM) phase following the safety follow-up phase. The study will end when all participants who were not treated with an alternative B-cell depleting therapy have repleted their B-cells to the baseline value or the lower limit of normal.

Arms & Interventions

Arms

Experimental: Ocrelizumab Higher Dose

Participants will be randomized to receive a minimum of 5 higher treatment doses (1200 mg or 1800 mg) of ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the double blind treatment (DBT) phase. During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Active Comparator: Ocrelizumab Approved Dose

Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Interventions

Drug: - Ocrelizumab

The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (participants's body weight <75 kg) or 1800 mg (participant's body weight >/=75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion every 24 weeks.

Drug: - Ocrelizumab

Ocrelizumab will be administered at a dose of 600 milligram (mg) every 24 weeks. The first dose of ocrelizumab will be administered as two 300 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion every 24 weeks.

Drug: - Antihistamine

Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

Drug: - Methylprednisolone

Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Worcester, Massachusetts

Status

Active, not recruiting

Address

University of Massachusetts Medical School

Worcester, Massachusetts, 01655

Site Contact

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