Comparative Study of Pharmacokinetics, Pharmacodynamics, and Safety of ABP 692 and Ocrelizumab in Relapsing-Remitting Multiple Sclerosis

The primary objective of this study is to demonstrate the **pharmacokinetic (PK)** similarity between ABP 692 and ocrelizumab (US), as well as between ABP 692 and ocrelizumab (EU). Additionally, the study aims to demonstrate the **pharmacodynamic (PD)** similarity between ABP 692 and ocrelizumab reference product (RP) based on the assessment of the suppression of new active brain lesions over 24 weeks. Establishing PK and PD similarity is clinically relevant as it ensures that ABP 692 can be considered a viable alternative to ocrelizumab, potentially offering similar therapeutic benefits in the management of **relapsing-remitting multiple sclerosis**.

The secondary objectives include:

• Comparing PK between ocrelizumab (US) and ocrelizumab (EU), ABP 692 and ocrelizumab (US), and ABP 692 and ocrelizumab (EU) following the initial dose.
• Descriptively comparing PK between the aforementioned groups.
• Descriptively comparing the total number of new or enlarging T2 hyperintense lesions and GdE T1-weighted lesions between ABP 692 and ocrelizumab RP over 24 weeks, and between different treatment sequences over 48 weeks.
• Descriptively comparing the total number of combined unique active (CUA) brain MRI lesions between ABP 692 and ocrelizumab RP treatment groups over 24 weeks, and between different treatment sequences over 48 weeks.
• Descriptively comparing the proportion of subjects achieving specific CD19+ B-cell levels between ABP 692 and ocrelizumab RP treatment groups at week 24, and between different treatment sequences at week 48.
• Descriptively comparing the proportion of subjects with relapse-free status at week 24 and week 48 between ABP 692 and ocrelizumab (US) and (EU), and between different treatment sequences.
• Assessing the safety and immunogenicity of ABP 692 compared with ocrelizumab (US) and ocrelizumab (EU).

The clinical trial involves a total of **142 participants** diagnosed with **Relapsing-remitting Multiple Sclerosis** (RRMS). The study population includes both male and female subjects, with an age range corresponding to adults. Participants were selected based on specific criteria, including a diagnosis of RRMS in accordance with the revised McDonald Criteria 2017, an Expanded Disability Status Scale score between 0 and 5.5, evidence of recent MS activity, and neurological stability with no relapse within 28 days prior to randomization. The trial does not include a vulnerable population. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The selection process ensures a representative sample of individuals with RRMS, focusing on those who meet the outlined clinical criteria.

The clinical trial is designed as a **randomized**, **double-blind**, parallel-group study aimed at comparing the pharmacokinetics, pharmacodynamics, clinical effects, and safety between ABP 692 and **Ocrevus** (ocrelizumab) in subjects with **relapsing-remitting multiple sclerosis**. The trial will involve intravenous infusion of the investigational products, with a maximum treatment period of 48 weeks. The primary objective is to demonstrate pharmacokinetic and pharmacodynamic similarity between ABP 692 and ocrelizumab, focusing on the suppression of new active brain lesions over a 24-week period. The trial is expected to commence recruitment on March 15, 2025, and conclude by July 2, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of relapsing-remitting multiple sclerosis according to the revised McDonald Criteria 2017, and an Expanded Disability Status Scale score between 0 and 5.5. Following randomization, participants will receive the initial dose, with pharmacokinetic assessments conducted up to day 15. Subsequent follow-up visits will occur at weeks 4, 8, 12, 16, 20, and 24 to monitor the total number of new GdE T1-weighted lesions via brain MRI. The end-of-study visit will mark the completion of the trial for each participant.

The expected length of participant involvement is approximately 48 weeks, contingent upon adherence to the study protocol. Conditions that may lead to early termination from the study include significant protocol deviations, adverse events, or withdrawal of consent by the participant. The trial is not categorized as low intervention and is part of a global clinical development program for ABP 692, a biosimilar investigational medicinal product. The study is crucial for establishing biosimilarity and supporting the path to commercialization of ABP 692.

The clinical trial involves the administration of **Ocrevus**, a **solution for infusion** containing the active substance **ocrelizumab**. Ocrevus is provided by AMGEN INC and is administered via **intravenous infusion**. The pharmaceutical form is a solution specifically designed for infusion, ensuring the precise delivery of the active substance. The treatment period for Ocrevus is set at a maximum of 48 weeks. The dosage is measured in milligrams per milliliter (mg/ml), although specific daily and total dose amounts are not detailed in the trial data. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

Another treatment used in the trial is **ABP 692**, also provided by AMGEN INC. This is a **concentrate for solution for infusion**, containing the same active substance, **ocrelizumab**. Like Ocrevus, ABP 692 is administered through **intravenous infusion**. The trial aims to compare the pharmacokinetics and pharmacodynamics of ABP 692 with Ocrevus, focusing on the suppression of new active brain lesions over a 24-week period. The maximum treatment period for ABP 692 is also 48 weeks, with dosing measured in mg/ml. Compliance monitoring is implemented to ensure participants adhere to the treatment regimen.

The trial also includes a comparator treatment, **Ocrevus 300 mg concentrate for solution for infusion**, provided by ROCHE REGISTRATION GMBH. This product is similarly administered via **intravenous infusion** and contains **ocrelizumab** as the active substance. The pharmaceutical form is a concentrate for solution for infusion, and the treatment period is capped at 48 weeks. The trial seeks to demonstrate pharmacokinetic and pharmacodynamic similarity between ABP 692 and this version of Ocrevus. As with the other treatments, dosing is measured in mg/ml, and participant compliance is closely monitored to maintain the integrity of the study results.

Efficacy in this clinical trial will be assessed through several primary endpoints, focusing on pharmacokinetic (PK) and pharmacodynamic (PD) parameters, as well as clinical effects in subjects with **relapsing-remitting multiple sclerosis**. The primary endpoints include the area under the serum concentration-time curve (AUC) from time 0 to day 15 (AUC0-d15) following infusion 1 of the initial dose, and the AUC from time 0 extrapolated to infinity (AUC0-inf) of the entire initial dose. Additionally, the total number of new gadolinium-enhancing (GdE) T1-weighted lesions will be assessed by brain MRI over weeks 4, 8, 12, 16, 20, and 24.

The trial is designed to demonstrate PK and PD similarity between ABP 692 and ocrelizumab, with a focus on the suppression of new active brain lesions over a 24-week period. Efficacy assessments will be conducted at specified timepoints, including weeks 4, 8, 12, 16, 20, and 24, using validated imaging techniques to quantify new GdE T1-weighted lesions. These assessments will provide critical data on the clinical effects and safety of ABP 692 compared to Ocrevus® (ocrelizumab), contributing to the overall evaluation of biosimilarity in this study.