A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing Orelabrutinib to Placebo in Patients With Non-active Secondary Progressive Multiple Sclerosis

Plain English Summary

A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis is a Phase 3 clinical trial sponsored by Zenas BioPharma (USA), LLC studying Secondary Progressive Multiple Sclerosis. This trial tests if Orelabrutinib can slow disability progression in adults with a specific type of Multiple Sclerosis (MS). It is for patients diagnosed with non-active Secondary Progressive Multiple Sclerosis (SPMS). Participants will take either Orelabrutinib or a placebo (inactive pill) for up to 5 years, with regular check-ups. Standard MS treatments and therapies may be available as alternatives depending on individual circumstances. The trial aims to enroll 990 participants.

Official Summary

Orelabrutinib is a CNS-penetrable BTK inhibitor. This is a phase 3, randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of orelabrutinib compared with placebo in patients with non-active Secondary Progress MS. Patients will be treated for approximately 24 to 60 months, with a minimum treatment duration of 12 months. The study will enroll approximately 990 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18-60 with a confirmed diagnosis of SPMS. Must have shown signs of disability worsening over the last 2 years, but no relapses in the last 24 months. Cannot have primary progressive MS, certain other neurological conditions, or active infections. Individuals on specific medications (like blood thinners or certain immune suppressors) or with a history of cancer may not be eligible. This trial is studying Secondary Progressive Multiple Sclerosis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if Orelabrutinib can delay the time it takes for confirmed disability to worsen, meaning it could help patients maintain their physical abilities for longer. The specific primary outcome measures are: Time to onset of confirmed disability progression (CDP) events, confirmed over at least 24 weeks (Up to approximately 120 weeks). 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 critical need for new treatments to slow the irreversible disability progression in Secondary Progressive Multiple Sclerosis, a condition with limited effective options. 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 Secondary Progressive Multiple Sclerosis, where improved treatment options are needed.

Investor Insight

Orelabrutinib targets a key pathway in MS, and a successful Phase 3 trial could position it as a significant new therapy in the large and growing MS market, potentially offering a competitive advantag Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 990 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if your specific type of MS and progression history make you a candidate for this trial. Participation involves regular clinic visits, MRI scans, and taking study medication daily for up to 5 years. Be prepared for potential monitoring of blood work and neurological assessments throughout the study. This trial is currently recruiting participants. The trial is being conducted at 1 site. 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: QUADRUPLE
• Enrollment: 990 participants

Interventions

• DRUG: Orelabrutinib — Orelabrutinib orally
• DRUG: Placebo — Placebo orally

Primary Outcomes

• Time to onset of confirmed disability progression (CDP) events, confirmed over at least 24 weeks (Up to approximately 120 weeks)

Secondary Outcomes

• 12 Week CDP (Up to approximately 120 weeks)
• T2 lesions on MRI (Up to approximately 120 weeks)
• 24-week CDP-9-hole Peg Test (Up to approximately 120 weeks)
• 24-week CDP-T25FWT (Up to approximately 120 weeks)
• 24-week CDI (Up to approximately 120 weeks)

Full Eligibility Criteria

Inclusion Criteria:

1. 18 to 60 years of age, inclusive, at the time of signing the informed consent.
2. Participant must have a previous diagnosis of RRMS in accordance with 2024 McDonald criteria
3. Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013
4. Participant must have documented evidence of disability progression independent of clinical relapse observed during the 24 months before screening. A written summary of the clinical evidence of disability progression must be discussed and aligned between the Investigator and the Sponsor's dedicated qualified person(s).
5. Absence of clinical relapses for at least 24 months.

Exclusion Criteria:

1. The patient has been diagnosed with primary progressive MS (PPMS) according to 2024 McDonald diagnostic criteria
2. Immunologic disorder other than MS or any other conditions requiring corticosteroid therapy.
3. History or current diagnosis of other neurological disorders that may mimic MS
4. History or current diagnosis of progressive multifocal leukoencephalopathy
5. Active, clinically significant viral, bacterial, or fungal infection
6. History of any other significant active medical condition
7. History of suicidal behavior within 6 months prior to Screening
8. Any prior history of malignancy
9. Patients on anticoagulation, or antiplatelet therapy
10. Patients took strong/moderate CYP3A inhibitors or strong/moderate CYP3A inducers within 14 days
11. Clinically significant laboratory abnormalities at Screening.
12. Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
13. History of alcohol abuse or alcohol use disorder or other drug abuse within 12 months prior to screening.

Trial Locations

• Neurology Associates, Maitland, Florida, United States

Frequently Asked Questions

Related Conditions

• Multiple Sclerosis
• Secondary Progressive Multiple Sclerosis
• Relapsing-Remitting Multiple Sclerosis
• Neurological Disorders
• Autoimmune Diseases
• Inflammatory Diseases
• Central Nervous System Diseases
• Neurodegenerative Diseases
• Immunology
• Oncology (due to exclusion criteria related to malignancy)

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