A Phase II, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Bioequivalence of Two Subcutaneous Formulations of Ocrelizumab in Patients with Multiple Sclerosis

The primary objective of this study is to assess the bioequivalence of the ocrelizumab subcutaneous test formulation to the ocrelizumab subcutaneous reference formulation. This comparison is clinically relevant to establish that the test formulation delivers equivalent systemic exposure to the reference formulation in patients with multiple sclerosis, thereby supporting potential alternative subcutaneous administration options for this therapeutic agent.

The secondary objective is to evaluate the safety and tolerability of the ocrelizumab subcutaneous test formulation compared to the ocrelizumab subcutaneous reference formulation.

This clinical trial enrolled a total of **96 participants** diagnosed with **multiple sclerosis**, specifically either **relapsing multiple sclerosis** or **primary progressive multiple sclerosis**, as defined by the revised McDonald 2017 criteria or the most current McDonald criteria at the time of study initiation. The study population consisted of both **male and female participants** aged **18 to 65 years** at the time of informed consent. Participants were required to have an **Expanded Disability Status Scale** score ranging from **0 to 6.5** at screening. Female participants of **childbearing potential** were included with the requirement to remain abstinent or use adequate contraception during the treatment period and for 6 months following the final dose of ocrelizumab, while postmenopausal female participants without childbearing potential were also eligible for enrollment. The trial included a vulnerable population as part of its design. The sponsor did not provide detailed information regarding specific lifestyle considerations such as diet, physical activity, or habits for this participant cohort.

This is a Phase II, randomized, open-label, parallel group, multicenter study designed to assess the **bioequivalence** of two **subcutaneous formulations** of **ocrelizumab** in patients with **multiple sclerosis**. The trial employs a randomized design with parallel treatment groups to compare a test formulation against a reference formulation of ocrelizumab administered via subcutaneous injection. The study is open-label, meaning that both participants and investigators are aware of the treatment assignment. The trial is planned to commence recruitment in January 2026 with an estimated completion date in December 2029, providing an overall trial duration of approximately four years.

The primary objective of the study is to establish bioequivalence between the ocrelizumab subcutaneous test formulation and the ocrelizumab subcutaneous reference formulation. The primary pharmacokinetic parameters assessed include the **area under the serum concentration-time curve** (AUC) and the **maximum serum concentration observed** (Cmax) of ocrelizumab. Secondary endpoints focus on safety assessments, including the incidence and severity of **adverse events** as determined by the **National Cancer Institute Common Terminology Criteria for Adverse Events** (NCI CTCAE) version 5 grading scale, changes from baseline in selected vital signs, and changes from baseline in selected clinical laboratory test results.

Eligible participants include individuals aged 18 to 65 years with a diagnosis of **relapsing multiple sclerosis** (RMS) or **primary progressive multiple sclerosis** (PPMS) according to the revised McDonald 2017 criteria or the most current McDonald criteria at the time of study initiation. Participants must have an **Expanded Disability Status Scale** (EDSS) score between 0 and 6.5, inclusive, at screening. Female participants of childbearing potential must agree to remain abstinent or use adequate contraception during the treatment period and for six months following the final dose of ocrelizumab. Postmenopausal female participants without childbearing potential may be enrolled.

The investigational medicinal product consists of ocrelizumab solution for injection administered via the subcutaneous route. The test formulation is Ocrevus 920 mg solution for injection, with a maximum daily dose of 920 mg and a maximum total dose of 3680 mg over a treatment period of 144 weeks. The comparator is the reference formulation of ocrelizumab subcutaneous solution for injection. Both formulations contain ocrelizumab as the active substance, which is classified as a protein of other origin.

Participant involvement in the study extends over the duration of the treatment period, which is up to 144 weeks for the test formulation. The study includes a screening visit to assess eligibility criteria, followed by scheduled study visits for treatment administration, pharmacokinetic sampling, and safety assessments. Follow-up visits are conducted to monitor adverse events, vital signs, and laboratory parameters throughout the study period. An end-of-study visit is performed to complete final safety evaluations and assessments. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol violations, adverse events requiring discontinuation, or investigator decision based on safety concerns.

This clinical trial evaluates two subcutaneous formulations of ocrelizumab in patients with multiple sclerosis. The study is designed as a randomized, open-label, parallel group, multicenter trial to assess bioequivalence between a test formulation and a reference formulation of the investigational medicinal product.

The test formulation consists of Ocrevus 920 mg solution for injection containing ocrelizumab as the active substance. This medicinal product is administered via the subcutaneous route. The maximum daily dose is 920 mg, with a maximum total dose of 3680 mg over the treatment period. The maximum treatment duration is 144 weeks. The active substance, ocrelizumab, is a protein-based therapeutic agent classified under ATC code L04AG08. The sponsor product code for this formulation is Ro 4964913.

The comparator formulation is Ocrevus containing ocrelizumab as the active substance, also presented as a solution for injection. This reference formulation is administered via the subcutaneous route. The sponsor product code for this formulation is RO 496-4913/F12-01. Both formulations contain the same active substance, ocrelizumab, which is of protein origin, and are manufactured by companies within the Roche group.

The primary objective of the trial is to assess bioequivalence of the ocrelizumab subcutaneous test formulation to the ocrelizumab subcutaneous reference formulation. Both products are administered subcutaneously and are formulated as solutions for injection, allowing for comparison of their pharmacokinetic profiles and therapeutic equivalence in the target patient population.

The primary efficacy parameters for this clinical trial are the pharmacokinetic parameters of ocrelizumab, specifically the area under the serum concentration-time curve (AUC) and the maximum serum concentration observed (Cmax). These parameters will be used to assess bioequivalence between the ocrelizumab subcutaneous test formulation and the ocrelizumab subcutaneous reference formulation in patients with multiple sclerosis.

Secondary endpoints include the incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 grading scale. Additional secondary assessments comprise change from baseline in selected vital signs and change from baseline in selected clinical laboratory test results.