Ocrelizumab for Progressive Multiple Sclerosis

(CONSONANCE Trial)

Recruiting at 214 trial locations

Overseen By Reference Study ID Number: MN39159 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: B-cell therapies, Alemtuzumab, Corticosteroids, others

Disqualifiers: RRMS, Pregnancy, Immunodeficiency, 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: Unknown

Duration: 192 weeks

927 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a prospective, multicenter, open-label, single-arm effectiveness and safety study in participants with progressive multiple sclerosis (PMS).

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. For example, if you've taken teriflunomide, you need a washout period (time without the medication) or an accelerated elimination procedure. Other medications like siponimod, natalizumab, and systemic corticosteroids also have specific timeframes for discontinuation before the trial.

What data supports the effectiveness of the drug Ocrelizumab for Progressive Multiple Sclerosis?

Ocrelizumab has been shown to reduce the risk of disability progression in patients with primary progressive multiple sclerosis (PPMS) in the ORATORIO trial, and it is more effective than interferon in reducing relapse rates in relapsing multiple sclerosis (RMS). It is generally well tolerated and offers a convenient treatment schedule with infusions every six months. ^{1 2 3 4 5}

Is ocrelizumab safe for humans?

Ocrelizumab, also known as Ocrevus, has been studied for its safety in treating multiple sclerosis, including both relapsing and primary progressive forms. Clinical trials and real-world studies have monitored its safety for up to 7 years, providing a comprehensive safety profile for its use in humans. ^{6 7 8 9 10}

What makes the drug Ocrelizumab unique for treating progressive multiple sclerosis?

Ocrelizumab is unique because it is the first drug approved for early primary progressive multiple sclerosis (PPMS), offering a convenient treatment with infusions only twice a year. It works by targeting and depleting B cells, which are involved in the disease process, and has shown effectiveness in reducing disease progression compared to placebo. ^{1 2 3 10 11}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with Progressive Multiple Sclerosis (PMS) who've had disability progression in the last 2 years, can use a smartphone with Wi-Fi, and have an EDSS score of 6.5 or less. Women must agree to contraception during treatment and afterward. Exclusions include recent other MS treatments, severe immune conditions, certain drug intolerances, active infections, pregnancy, or previous ocrelizumab use.

Inclusion Criteria

Have a documented evidence of disability progression independent of relapse at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician's judgment

Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers

Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist

Exclusion Criteria

I haven't taken any corticosteroids in the last 4 weeks.

History or currently active primary or secondary immunodeficiency

I've had treatments targeting B-cells, but not rituximab in the last 6 months, and my B-cell levels are normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Ocrelizumab is administered via intravenous infusion to participants with progressive multiple sclerosis

192 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• Ocrelizumab

Trial Overview The study tests Ocrelizumab's effectiveness and safety in treating PMS. It's an open-label trial where all participants receive the drug; there are no comparison groups. The focus is on how well it works over time and what side effects occur.

Participant Groups

Group I: Ocrelizumab Experimental Treatment 1 Intervention

Ocrelizumab will be administered via intravenous (IV) 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

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 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]

In a post hoc analysis of pivotal trials, ocrelizumab significantly reduced the risk of confirmed disability progression in multiple sclerosis patients with higher baseline disability (Expanded Disability Status Scale scores ≥4.0).

The analysis included patients from the OPERA trials (relapsing MS) and ORATORIO trial (primary progressive MS), showing that ocrelizumab was more effective than interferon β-1a and placebo in slowing disability progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. Wolinsky, JS., Engmann, NJ., Pei, J., et al.[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]

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]

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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. [2023]

3. Egypt pubmed.ncbi.nlm.nih.gov

Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Severe Delayed-Onset Neutropenia Induced by Ocrelizumab. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

Ocrelizumab: its efficacy and safety in multiple sclerosis. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomised, placebo-controlled, phase 3 trial. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. [2018]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: First Global Approval. [2022]