A Phase IIIB Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

Plain English Summary

A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS) is a Phase 3 clinical trial sponsored by Hoffmann-La Roche studying Multiple Sclerosis. Tests a higher dose of ocrelizumab to slow disability progression in adults with primary progressive multiple sclerosis (PPMS). For adults with PPMS who have had symptoms for less than 15 years and a specific EDSS score. Participation involves IV infusions every 24 weeks, with premedication to prevent reactions. No alternative treatments are currently available for PPMS. The trial aims to enroll 769 participants.

Official Summary

This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with PPMS, EDSS score 3-6.5, and specific T25FWT and 9HPT scores. Not eligible if history of relapsing remitting or secondary progressive MS, cancer, or immunocompromised state. Age range: 18-75 years. Health requirements: Stable disease, no active infections, and no other neurologic disorders. This trial is studying Multiple Sclerosis, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the time to onset of disability progression, which means it tracks how long it takes for participants' disability to worsen by at least 20%. The specific primary outcome measures are: Time to Onset of Composite Confirmed Disability Progression (cCDP) Sustained for at least 12 Weeks (Baseline up to approximately 4.3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a significant gap in treatment options for PPMS, offering a higher dose of ocrelizumab to potentially slow disability progression. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Multiple Sclerosis, where improved treatment options are needed.

Investor Insight

The large market size and lack of approved treatments for PPMS make this trial highly significant, with a high probability of approval if successful. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 769 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you meet the eligibility criteria for PPMS and have a specific EDSS score. Participation involves IV infusions every 24 weeks and premedication to prevent reactions. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 769 participants

Interventions

• DRUG: Ocrelizumab — The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight \<75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W. During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1
• DRUG: Ocrelizumab — Ocrelizumab will be administered at a dose of 600 mg Q24W. The first dose of ocrelizumab will be administered as two 300 mg, IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion Q24W.
• 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.

Primary Outcomes

• Time to Onset of Composite Confirmed Disability Progression (cCDP) Sustained for at least 12 Weeks (Baseline up to approximately 4.3 years)

Secondary Outcomes

• Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) Independent of Protocol-defined Relapses (PDR) (Baseline up to approximately 4.3 years)
• Time to Onset of 12-week Confirmed Disability Progression (CDP12) (Baseline up to approximately 4.3 years)
• Time to ≥ 20% Increase in 12-week Confirmed by T25FWT (Baseline up to approximately 4.3 years)
• Change in Neurofilament Light (NfL) at Week 96 (Baseline up to Week 96)
• Time to 12-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS12) (Baseline up to approximately 4.3 years)

Full Eligibility Criteria

Inclusion Criteria:

* Diagnosis of PPMS
* 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 (FS) scale for the pyramidal system that was due to lower extremity findings at screening and baseline
* Documented magnetic resonance imaging (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 ≤ 5, disease duration must be less than 10 years; If EDSS score at screening is \> 5, disease duration must be less than 15 years
* Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands
* Females of childbearing potential: agreement to remain abstinent or use adequate contraceptive methods
* Female participants, without reproductive potential may be enrolled e.g. if post-menopausal 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 infusion-related reaction (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-cluster of differentiation 20 (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 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 Locations

• Alabama Neurology Associates, Homewood, Alabama, United States
• 21st Century Neurology, Phoenix, Arizona, United States
• University of California Irvine, Irvine, California, United States
• Stanford University Medical Center, Stanford, California, United States
• University of Colorado Denver, Aurora, Colorado, United States
• Advanced Neurosciences Research LLC, Fort Collins, Colorado, United States
• MS and Neuromuscular Center of Excellence, Clearwater, Florida, United States
• University of South Florida, Tampa, Florida, United States
• Baptist Health Lexington, Nicholasville, Kentucky, United States
• International Neurorehabilitation Institute, Lutherville, Maryland, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Multiple Sclerosis
• Primary Progressive Multiple Sclerosis
• Secondary Progressive Multiple Sclerosis
• Relapsing-Remitting Multiple Sclerosis
• Neurology
• Immunology
• Pharmacology

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