An Efficacy and Safety Study With Integrated Pharmacokinetics (PK) and Pharmacodynamic (PD) Assessment to Compare the Proposed Ocrelizumab Biosimilar CYB704 and Ocrevus in Participants With Relapsing Multiple Sclerosis (RMS)

Phase 3

Not yet recruiting

• Conditions: Relapsing Multiple Sclerosis
• Interventions: Biological: CYB704; Biological: Ocrevus-EU; Biological: Ocrevus-US

• Registration Number: NCT06847724
• Lead Sponsor: Sandoz

Brief Summary

The goal of this clinical trial is to learn if drug CYB704, a proposed biosimilar to Ocrevus, works to treat multiple sclerosis in the same way as the reference product Ocrevus(R).

The main questions it aims to answer are:

* Is CYB704 distributed in the body in the same way as the reference product (demonstration of pharmacokinetic (PK) similarity)?

* Does have CYB704 the same treatment effect and side effects as the reference product?

Researchers will compare CYB704 to a Ocrevus (Ocrevus-US and Ocrevus-EU) (Participants will:

* Take drug CYB704 or Ocrevus (Ocrevus-US and Ocrevus-EU)

* Visit the clinic for a t least 15 treatment visits, checkups and tests

* Will undergo regular magnetic resonance imaging (MRI) examinations

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-02-25
• Last Update Submitted: 2025-02-25
• Study First Posted: 2025-02-26
• Last Update Posted: 2025-02-26
• Study Start: 2025-04-14
• Primary Completion: 2027-05-14
• Study Completion: 2029-10-14

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 518

Inclusion Criteria

• Diagnosis of RMS (relapsing remitting multiple sclerosis (MS) and active secondary progressive MS)
• Evidence of recent disease activity as defined in study protocol
• Expanded Disability Status scale score of 0 to 5.5 (inclusive) at screening
• Neurological stability (no new signs or symptoms referable to Central Nervous System (CNS) within 30 days before both screening and first study treatment

Exclusion Criteria

• Diagnosis of primary progressive MS
• Disease duration of more than 10 years in participants with an Expanded Disability Status Scale (EDSS) ≤2.0 at screening
• Inability to complete an MRI or contraindication to gadolinium administration
• History of allergic or anaphylactic reactions to ocrelizumab or one of the premedications (methylprednisolone or equivalent corticosteroid, antihistamine, antipyretic)
• Pregnant participants
• Current or history of medical conditions as outlined in the study protocol
• Prohibited medications (current and history) as outlined in the study protocol
• Abnormal laboratory blood values as outlined in the study protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CYB704	CYB704	Drug: CYB704 (Ocrelizumab) Patients will be dosed 300 mg on day 1 and day 15. Subsequent dose of 600 mg will be administered 24 weeks after the initial dose.
Ocrevus-EU	Ocrevus-EU	Drug: Ocrevus-EU Patients will be dosed 300 mg on day 1 and day 15. Subsequent dose of 600 mg will be administered 24 weeks after the initial dose.
Ocrevus-US	Ocrevus-US	Drug: Ocrevus-US Patients will be dosed 300 mg on day 1 and day 15. Subsequent dose of 600 mg will be administered 24 weeks after the initial dose.

Primary Outcome Measures

Name	Time	Method
Area under the concentration time curve in cohort 1	Week 1 - 3, week 3 - 25	Demonstrate similar PK between Ocrevus-US, Ocrevus-EU, and CYB704
Total number of T1-weighted Gadolinium enhancing (GdE) lesions on brain MRI scans	Up to 24 weeks	Demonstrate similar efficacy between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve (AUC) in cohort 1	Week 1 - 25	Compare PK between Ocrevus-US, Ocrevus-EU, and CYB704
Peak Plasma Concentration (Cmax) in cohort 1	Day 1 and Day 15	Demonstrate similar PK between Ocrevus-US, Ocrevus-EU, and CYB704
CD19+ B-cell count	Up to 48 weeks	Compare PD between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704
Total number of new/enlarging T2 lesions	Up to 48 weeks	Compare efficacy between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704
Total number of new T1 GdE lesions	Up to 48 weeks	Compare efficacy between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704
Annualized Relapse Rate	Up to 48 weeks	Compare efficacy between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704
Treatment emergent Adverse Events and Serious Adverse Events	Up to 48 weeks	Compare safety between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704
Rate of patients with anti-drug antibodies	Up to 48 weeks	Compare immunogenicity between Ocrevus (Ocrevus-US and Ocrevus-EU) and CYB704