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Number of Visits: 9

769 Participants Needed

High-Dose Ocrelizumab for Multiple Sclerosis
(GAVOTTE Trial)

Recruiting at 246 trial locations

Overseen ByReference 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 GroupAll 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 DataThis treatment has passed at least one previous human trial

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

Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial is testing if a higher dose of ocrelizumab given through an IV drip is more effective and safe for patients with Primary Progressive Multiple Sclerosis (PPMS). The drug works by reducing harmful immune cells to potentially slow down the disease. Ocrelizumab is the first drug approved for treating both relapsing and primary progressive forms of multiple sclerosis.

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.

What data supports the effectiveness of the drug Ocrelizumab for multiple sclerosis?

Ocrelizumab has been shown to reduce relapse rates and disease activity in patients with relapsing multiple sclerosis and to delay disease progression in primary progressive multiple sclerosis. Clinical trials demonstrated its effectiveness compared to other treatments, and it is generally well tolerated with manageable side effects.¹ ² ³ ⁴ ⁵

Is high-dose ocrelizumab safe for humans?

Ocrelizumab, also known as Ocrevus, has been studied for multiple sclerosis and is generally considered safe, but it can cause side effects like delayed-onset neutropenia (a drop in white blood cells that fight infection). Safety data is still being collected through ongoing studies and reports.² ³ ⁴ ⁶ ⁷

How is the drug Ocrelizumab unique for treating multiple sclerosis?

Ocrelizumab is unique because it is the first drug approved for early primary progressive multiple sclerosis, a form of the disease with no other approved treatments. It works by targeting and depleting B cells, which are involved in the disease process, and is administered as an intravenous infusion every six months, offering convenience compared to more frequent dosing schedules of other treatments.² ³ ⁴ ⁵ ⁸

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

See 14 more

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.

See 26 more

Timeline

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

Treatment Details

Interventions

Ocrelizumab

Trial OverviewThe 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.

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: Ocrelizumab Higher DoseExperimental Treatment3 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 DoseActive Control3 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

Find a Clinic Near You

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

Findings from Research

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 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, 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]