A Double-blind, Randomized, Active-controlled, Parallel-group, Phase 1/3 study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics and Safety of CT-P53 and Ocrevus in Patients with Relapsing-remitting Multiple Sclerosis.

The primary objective of this study is to evaluate the pharmacokinetic (PK) comparability of CT-P53, EU-approved Ocrevus, and US-licensed Ocrevus in patients with relapsing-remitting multiple sclerosis (RRMS). Additionally, the study aims to demonstrate the non-inferiority of CT-P53 compared to the reference drug, which includes both EU-approved and US-licensed Ocrevus, in the same patient population. This is clinically relevant as it seeks to establish CT-P53 as a viable alternative to existing treatments, potentially offering more options for managing RRMS. Secondary objectives include: - Assessing additional PK and pharmacodynamic (PD) parameters of CT-P53, EU-approved Ocrevus, and US-licensed Ocrevus. - Evaluating the additional efficacy, PK, PD, and safety, including immunogenicity, of CT-P53 and the reference drug (EU-approved Ocrevus and US-licensed Ocrevus). These objectives are crucial for understanding the broader therapeutic profile and safety of CT-P53 in comparison to established treatments.

The clinical trial involves a total of 80 participants diagnosed with Multiple Sclerosis (MS), specifically focusing on individuals with relapsing-remitting MS (RRMS). The study population comprises both male and female subjects, aged between 18 and 55 years, who meet the revised McDonald criteria (2017) for MS diagnosis. Participants were selected based on their recent MS activity and neurological stability for at least 30 days, with an Expanded Disability Status Scale (EDSS) score ranging from 0 to 6.0. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria. The primary objective is to assess the pharmacokinetic comparability and non-inferiority of the investigational drug CT-P53 to the reference drug Ocrevus, approved in both the EU and the US, in this patient population. The sponsor has not provided additional information regarding lifestyle factors or other demographic details.

The clinical trial is designed as a randomized, double-blind, active-controlled, parallel-group, Phase 1/3 study. It aims to compare the efficacy, pharmacokinetics, pharmacodynamics, and safety of CT-P53 and Ocrevus in patients with relapsing-remitting multiple sclerosis. The trial is expected to commence recruitment on December 1, 2023, and conclude by February 19, 2027. The study involves two main groups: a pharmacokinetics (PK) group and a main study group. The primary objective for the PK group is to demonstrate the comparability of CT-P53 with EU-approved and US-licensed Ocrevus, while the main study group aims to establish the non-inferiority of CT-P53 compared to the reference drug. Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis of multiple sclerosis according to the revised McDonald criteria (2017), recent MS activity, neurological stability, and an EDSS score between 0 and 6.0. Following successful screening, participants will be randomized into treatment groups. The trial includes regular follow-up visits to monitor safety, efficacy, and pharmacokinetic parameters, with key assessments at Week 2, Week 24, and Week 48. The end-of-study visit will occur at the conclusion of the treatment period, which spans up to 96 weeks. Participant involvement is expected to last for the entire duration of the trial, approximately 96 weeks, unless early termination is warranted. Conditions that may lead to early withdrawal include adverse events, non-compliance with the study protocol, or withdrawal of consent. The primary endpoints for the PK group include the area under the concentration-time curve from time zero to Week 2 and from Week 2 to Week 24. For the main study group, the primary endpoint is the total number of new GdE lesions on T1-weighted brain MRI up to Week 48. The trial is not classified as low-intervention and is conducted under rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves several treatments, including Solu-Medrone, which is a methylprednisolone formulation provided as a powder and solvent for solution for injection or concentrate for solution for infusion. It is administered intravenously. The dosage is 125 mg per vial, with a maximum daily dose of 100 mg and a total maximum dose of 500 mg over a treatment period of up to 96 hours. This product is manufactured by Pfizer Healthcare Ireland and is not a pediatric formulation. Ocrelizumab is used in two forms within the trial. The first is a solution for infusion, with a maximum daily dose of 600 mg and a total maximum dose of 2400 mg over 96 hours. It is administered via intravenous infusion. The second form, CT-P53, is an investigational product also containing ocrelizumab, provided as an injection. It shares the same dosing parameters as the Ocrevus solution for infusion. Both forms are used to compare efficacy and safety in patients with relapsing-remitting multiple sclerosis. CT-P53 is produced by Celltrion, while Ocrevus is manufactured by Roche Registration GmbH. Zirtek, containing cetirizine dihydrochloride, is an oral solution used as an auxiliary treatment. It is administered orally with a maximum daily dose of 10 mg and a total maximum dose of 50 mg over the treatment period. This antihistamine is produced by UCB Pharma Ireland Ltd. Paracetamol is provided in tablet form, with each tablet containing 500 mg. It is used as an antipyretic and administered orally. The maximum daily dose is 60 mg/kg, with a total maximum dose of 300 mg/kg over 96 hours. This product is manufactured by HEXAL AG. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to demonstrate the pharmacokinetic comparability and non-inferiority of CT-P53 to the reference drug, Ocrevus, in patients with relapsing-remitting multiple sclerosis.

Efficacy in this clinical trial will be assessed through specific primary endpoints tailored to the study groups. For the Pharmacokinetics (PK) Group, efficacy will be evaluated by measuring the Area under the concentration-time curve from time zero to Week 2 (AUC0-wk2) and from Week 2 to Week 24 (AUCwk2-wk24). These parameters will provide insights into the pharmacokinetic comparability of CT-P53, EU-approved Ocrevus, and US-licensed Ocrevus in patients with Relapsing-remitting Multiple Sclerosis (RRMS). For the Main Study Group, the primary endpoint will be the total number of new Gadolinium-enhancing (GdE) lesions on T1-weighted brain MRI up to Week 48. This endpoint is crucial for demonstrating the non-inferiority of CT-P53 compared to the reference drug, Ocrevus. The schedule for measuring these endpoints includes specific timepoints, such as Week 2, Week 24, and Week 48, to ensure comprehensive data collection and analysis. The use of validated imaging techniques and pharmacokinetic assessments will be integral to the efficacy evaluation process.