Orelabrutinib for Multiple Sclerosis

Recruiting at 41 trial locations

Overseen By Olivia Yang

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Disqualifiers: Progressive MS, Immunologic disorder, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Orelabrutinib, a medication for people with Relapsing-Remitting Multiple Sclerosis. It aims to reduce immune cell activity that causes attacks on the nervous system, potentially lowering the frequency and severity of relapses.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes participants who have taken prohibited medications or treatments. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug Orelabrutinib for treating multiple sclerosis?

Orelabrutinib is similar to other drugs like evobrutinib and tolebrutinib, which are also Bruton's tyrosine kinase inhibitors. These drugs have shown promise in reducing inflammation and new brain lesions in multiple sclerosis, suggesting that Orelabrutinib might work similarly. ^{1 2 3 4 5}

Is Orelabrutinib safe for humans?

Research on Orelabrutinib combined with high-dose methotrexate for treating a type of lymphoma in elderly patients looked at short-term safety and found some adverse reactions (side effects), but specific details on these reactions are not provided in the summary. ^{1 6 7 8 9}

How is the drug Orelabrutinib unique for treating multiple sclerosis?

Orelabrutinib is a novel, small molecule drug that selectively inhibits Bruton's tyrosine kinase, an enzyme involved in immune cell signaling, which may help reduce inflammation in multiple sclerosis. This mechanism is similar to other drugs like evobrutinib and tolebrutinib, but Orelabrutinib's unique selectivity and irreversible binding make it a distinct option. ^{1 3 9 10 11}

Eligibility Criteria

This trial is for adults aged 18-55 with Relapsing Remitting Multiple Sclerosis (RRMS) who've had at least one relapse in the past two years and have an EDSS score of 0 to 5.5. Women must use contraception, and participants should be neurologically stable for over a month before starting.

Inclusion Criteria

I am between 18 and 55 years old.

I have been diagnosed with Relapsing Remitting Multiple Sclerosis.

My neurological condition has been stable for over a month.

Exclusion Criteria

I have an immune system disorder that is not multiple sclerosis.

You have a new health problem that showed up during the main part of the study.

I have had cancer before, but it was only skin cancer that was treated successfully.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Core Part Treatment

Participants receive either placebo or varying doses of orelabrutinib for 24 weeks

24 weeks

Open-label Extension

Participants who completed the Core Part continue treatment with orelabrutinib to collect long-term safety and efficacy data

up to 96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Orelabrutinib
• Placebo

Trial Overview The study tests Orelabrutinib against a placebo in a double-blind setup, meaning neither the patients nor the researchers know who's receiving the actual drug or placebo during the trial phase.

Participant Groups

Group I: orelabrutinib(medium dose) Experimental Treatment 1 Intervention

The Core Part ：Participants receive medium dose orelabrutinib The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.

Group II: orelabrutinib(low dose) Experimental Treatment 1 Intervention

The Core Part：Participants receive low dose orelabrutinib The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.

Group III: orelabrutinib (high dose) Experimental Treatment 1 Intervention

The Core Part：Participants receive high dose orelabrutinib The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.

Group IV: placebo Placebo Group 2 Interventions

The Core Part：Participants receive placebo The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.

Who Is Running the Clinical Trial?

Beijing InnoCare Pharma Tech Co., Ltd.

Lead Sponsor

Trials

48

Recruited

6,000+

Findings from Research

In a 16-week study involving 130 participants with relapsing multiple sclerosis, tolebrutinib demonstrated a dose-dependent reduction in new active brain lesions, with the highest efficacy observed at the 60 mg dose.

Tolebrutinib was well tolerated, with only one serious adverse event reported and no treatment-related deaths, suggesting it is a safe option for reducing inflammation in multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. Reich, DS., Arnold, DL., Vermersch, P., et al.[2023]

Evobrutinib, a Bruton's tyrosine kinase inhibitor, was generally well tolerated across multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus trials, with similar rates of treatment-emergent adverse events (TEAEs) compared to placebo (66.2% vs 62.4%).

The analysis included data from 1083 patients across various trials, revealing that serious infections and liver enzyme elevations were comparable between evobrutinib and placebo, indicating a favorable safety profile for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis. Montalban, X., Wallace, D., Genovese, MC., et al.[2023]

In a study of 128 multiple sclerosis patients, ocrelizumab was found to be well tolerated, with most side effects being mild and decreasing over time, indicating good short-term safety in a real-world setting.

The treatment also showed efficiency in stabilizing the disease, with no severe side effects reported, suggesting that ocrelizumab is a viable option for managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients. Prockl, V., Nickel, FT., Utz, KS., et al.[2021]

In a study of 228 multiple sclerosis patients treated with ocrelizumab, 91.2% of those with relapsing forms of MS achieved no evidence of disease activity (NEDA) after one year, indicating strong effectiveness in managing the disease.

The treatment was generally well-tolerated, with the most common side effects being infusion-related reactions and infections, particularly urinary tract infections, suggesting a favorable safety profile in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. Fernandez-Diaz, E., Perez-Vicente, JA., Villaverde-Gonzalez, R., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton's tyrosine kinase inhibitor. [2023]

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

Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Disability progression markers over 6-12 years in interferon-β-treated multiple sclerosis patients. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of multiple sclerosis with rituximab: A multicentric Italian-Swiss experience. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients. [2021]

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

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. [2021]

9. China pubmed.ncbi.nlm.nih.gov

[Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma]. [2023]

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

Evaluation of orelabrutinib monotherapy in patients with relapsed or refractory Waldenström's macroglobulinemia in a single-arm, multicenter, open-label, phase 2 study. [2022]

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

CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS. [2021]