High-Dose Ocrelizumab for Multiple Sclerosis

(GAVOTTE Trial)

Not currently recruiting at 299 trial locations

Overseen By Reference Study ID Number: BN42083 https://forpatients.roche.com/

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Corticosteroids, CD20s, others

Disqualifiers: Cancer, Immunocompromised, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a higher dose of ocrelizumab (marketed as Ocrevus), administered through an IV every 24 weeks, is more effective and safe for individuals with primary progressive multiple sclerosis (PPMS) compared to the standard dose. Ocrelizumab aims to slow the progression of MS, a condition where the immune system attacks the protective covering of nerves. Participants will receive either the higher dose or the standard dose, and the trial will compare the outcomes. This trial may suit individuals diagnosed with PPMS who have had the condition for up to 10-15 years, depending on certain criteria affecting mobility. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants stop certain medications before joining. For example, previous treatments with specific MS drugs like fingolimod, siponimod, or ozanimod must be stopped 6 weeks before starting the trial. Other medications may also require a 'washout period' (time without taking certain medications) as specified in the trial details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the higher dose of ocrelizumab is generally well-tolerated, with safety results similar to the usual 600 mg dose. Earlier studies demonstrated that both doses slowed disability progression in patients. However, individuals taking ocrelizumab experienced more infections compared to those on other treatments or a placebo. This indicates that while the treatment is effective, monitoring for infections is crucial. Overall, the safety profile of ocrelizumab aligns with past studies, making it a relatively safe option for treating multiple sclerosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Researchers are excited about high-dose ocrelizumab for multiple sclerosis because it offers a potentially more effective treatment by increasing the dosage based on body weight. Unlike the standard approved dose of 600 mg, this approach uses doses of 1200 mg or 1800 mg, which may enhance its ability to reduce disease activity and progression. This tailored dosing strategy could lead to better outcomes for patients with more aggressive forms of multiple sclerosis, offering new hope for improved management of the condition.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that ocrelizumab, at the standard 600 mg dose, effectively treats multiple sclerosis by slowing disability progression by about 30%. This treatment also reduces the number of relapses, demonstrating its effectiveness.

In this trial, participants will receive either the approved 600 mg dose or a higher dose of ocrelizumab. Studies indicate that the higher dose maintains similar low rates of disability worsening. However, clear evidence does not support additional benefits from the higher dose compared to the standard dose. Overall, ocrelizumab effectively manages multiple sclerosis symptoms. ^{1 2 3 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with Primary Progressive Multiple Sclerosis (PPMS) who have specific MRI brain abnormalities, a stable neurological condition for at least 30 days before the trial, and an EDSS score between 3 to 6.5. Disease duration must be under 10 years for lower EDSS scores or under 15 years for higher scores. Women of childbearing potential must use contraception; those without reproductive potential can also join.

Inclusion Criteria

My disability score is between 3 and 6.5.

My MS symptoms started less than 10 years ago if my disability score is 5 or less, or less than 15 years ago if my score is over 5.

My walking test score is 150 seconds or less.

Exclusion Criteria

I have had a bone marrow or stem cell transplant.

I meet all specific requirements for ocrelizumab treatment as per my local guidelines.

My immune system is weakened.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive ocrelizumab every 24 weeks for a minimum of 120 weeks

120 weeks

5 visits (in-person)

Open-label Extension

Eligible participants continue with a higher dose of ocrelizumab for approximately 96 weeks

96 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety for 48 weeks after treatment

48 weeks

B-cell Monitoring

Participants whose B-cell levels have not repleted to baseline or LLN are monitored until repletion

What Are the Treatments Tested in This Trial?

Interventions

• Ocrelizumab

Trial Overview The study is testing whether a higher dose of Ocrelizumab given every six months is more effective than the approved standard dose in treating PPMS. It's randomized and double-blind, meaning participants are put into groups by chance and neither they nor the researchers know who gets which dose.

How Is the Trial Designed?

Group I: Ocrelizumab Higher Dose Experimental Treatment 3 Interventions

Participants will be randomized to receive a minimum of 5 higher treatment doses based on their body weight at baseline: 1200 mg (participant's body weight \<75 kilograms \[kg\]) or 1800 mg (participant's body weight ≥ 75 kg) of ocrelizumab administered by IV infusion Q24W in the DBT phase. During the optional 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.

Group II: Ocrelizumab Approved Dose Active Control 3 Interventions

Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by IV infusion Q24W 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.

Ocrelizumab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Approved in European Union as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Approved in Canada as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Ocrelizumab is a humanized anti-CD20 monoclonal antibody specifically designed to deplete B cells, which are implicated in the development of multiple sclerosis (MS).

Approved in March 2017 in the USA for treating both relapsing and primary progressive forms of MS, ocrelizumab represents a significant advancement in MS therapy, with its approval in the EU currently pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: First Global Approval. Frampton, JE.[2022]

Ocrelizumab is the first approved treatment for both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS), demonstrating significant efficacy in slowing disability progression in PPMS patients at 12 and 24 weeks.

The safety profile of ocrelizumab aligns with findings from clinical trials, showing no unexpected safety concerns, which supports its use in managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: its efficacy and safety in multiple sclerosis. Juanatey, A., Blanco-Garcia, L., Tellez, N.[2019]

Ocrelizumab is an effective treatment for both relapsing forms of multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), showing significant reductions in relapse rates and disease progression over at least 7.5 years of treatment.

The drug is generally well tolerated, with no new safety concerns identified during long-term use, and offers the convenience of infusions every six months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. Lamb, YN.[2023]

Ocrelizumab significantly reduces annualized relapse rates in adults with relapsing multiple sclerosis (RMS) compared to interferon β-1a, based on results from two 96-week trials.

In patients with primary progressive multiple sclerosis (PPMS), ocrelizumab significantly lowers the risk of confirmed disability progression over 120 weeks compared to placebo, and it is generally well tolerated with mostly mild to moderate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. Syed, YY.[2022]

Ocrelizumab is the first drug approved by the European Medicines Agency for treating both early primary progressive multiple sclerosis and relapsing forms of multiple sclerosis, highlighting its significance in MS treatment.

The review discusses the safety and effectiveness of ocrelizumab, indicating it has undergone rigorous evaluation to support its use in adults with multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. [2018]

Ocrelizumab, an anti-CD20 monoclonal antibody, is effective in reducing disability progression in primary progressive multiple sclerosis, but it can lead to severe late-onset neutropenia as a rare side effect.

In a reported case, a 34-year-old male developed severe neutropenia 42 days after receiving ocrelizumab, requiring hospitalization and treatment, highlighting the need for patient awareness and monitoring for symptoms like fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Delayed-Onset Neutropenia Induced by Ocrelizumab. Baird-Gunning, J., Yun, J., Stevenson, W., et al.[2022]

In a review of 78 studies involving 4498 patients, 61.3% of those treated with ocrelizumab experienced adverse events, with the most common being infections (39.2%) and infusion-related reactions (26.2%).

Ocrelizumab was associated with a higher risk of infections compared to beta-interferon, particularly herpes-related and respiratory infections, while the risk of serious adverse events was similar between ocrelizumab and comparator groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. Ng, HS., Rosenbult, CL., Tremlett, H.[2022]

Citations

1. ocrevus-hcp.com ocrevus-hcp.com/ocrevus/efficacy.html

Efficacy | OCREVUS® (ocrelizumab) In male patients, the proportion of patients with disability progression confirmed at 12 weeks after onset was approximately 30% in OCREVUS-treated patients and ...

2. gene.com gene.com/media/press-releases/15078/2025-09-23/genentech-presents-new-data-for-ocrevus-

Genentech: Press Releases | Tuesday, Sep 23, 2025 Ocrevus shows 30% reduction in the risk of time to onset of 12-week composite confirmed disability progression (cCDP) in adults with advanced ...

3. roche.com roche.com/investors/updates/inv-update-2025-04-02b

Roche provides update on Phase III OCREVUS high dose ... The rates of disability progression were low and consistent with rates observed in the previous pivotal studies of OCREVUS IV 600 mg. In ...

4. ocrevus.com ocrevus.com/patient/ocrevus-101/relapsing-multiple-sclerosis.html

OCREVUS® (ocrelizumab) Results for RMS (Relapsing MS) OCREVUS was proven effective at slowing disability progression compared with Rebif across 2 years. Disability progression was confirmed 3 months after the ...

5. neurologylive.com neurologylive.com/view/genentech-reports-high-dose-ocrelizumab-failed-show-additional-benefit-relapsing-ms

Genentech Reports High-Dose Ocrelizumab Fails to Show ... Ocrelizumab's 600 mg dose maintains low relapse rates, confirming its effectiveness as a treatment for multiple sclerosis.

6. gene.com gene.com/media/press-releases/15056/2025-04-02/genentech-provides-update-on-phase-iii-o

Genentech: Press Releases | Wednesday, Apr 2, 2025 The trial did not meet its primary endpoint; results support Ocrevus IV 600 mg as the optimal dose to slow disability progression.