GP2013 Treatment in Patients With Active Rheumatoid Arthritis, Previously Treated With Rituxan® or MabThera®

Study Overview
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Brief Summary
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The study objective is to identify potential safety risks of the transition from US-licensed Rituxan® or EU-approved MabThera® to GP2013 (proposed biosimilar product) as compared to continuous treatment with the originator product in terms of general safety and immunogenicity.

Official Title
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A Randomized, Double- Blind, Controlled, Parallel-group, Multicenter Study to Assess the Safety and Immunogenicity of Transitioning to GP2013 or Re-treatment With Rituxan® or MabThera® in Patients With Active Rheumatoid Arthritis, Previously Treated With Rituxan® or MabThera®

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: GP2013 - A Proposed biosimilar rituximab
* Biological: Originator rituximab - Rituxan ® or MabThera ®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of rheumatoid arthritis (RA) according to ACR 2010 criteria Completed one full treatment course with either Rituxan® or MabThera® Eligible for a further treatment course with Rituxan® or MabThera®- Currently treated with methotrexate Exclusion Criteria: RA functional status class IV (ACR 1991 revised criteria) Systemic manifestation of RA Positive serology for hepatitis B or hepatitis C infection Active systemic infection History of cancer Known severely immunocompromised state Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP2013 - proposed biosimilar rituximab<br>10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration, two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. The treatment course consists of 2 i.v. infusions 2 weeks apart (at Day 1 and Day 14). | Biological: GP2013 - A Proposed biosimilar rituximab<br> <br> |
| Active Comparator: Originator rituximab - Rituxan ® or MabThera ®<br>10 mg/mL in 500 mg (50 mL) single-use vials. For i.v. administration two 500 mg vials (1000 mg of active molecule) of concentrate are diluted in 0.9% NaCl solution and infused i.v. The treatment course consists of 2 i.v. infusions 2 weeks apart (at Day 1 and Day 14). | Biological: Originator rituximab - Rituxan ® or MabThera ®<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Experiencing Anaphylactic Reactions | 2006 NIAID/FAAN* criteria were used for identification of anaphylactic reactions within 24h of each study drug infusion. For patients with no history of infusion-related reactions during their previous treatments with rituximab, symptoms/signs in at least 2 out of 4 organ systems: Skin/mucosal tissue Respiratory organs Drop of systolic blood pressure (<90 mmHg or variance from baseline >30%) or associated symptoms Gastrointestinal organs were defined as an anaphylactic reaction. The same criteria were also applied to patients with history of infusion-related reactions during their previous treatments with rituximab. In addition, if these patients experienced only a rapid drop in systolic blood pressure (<90 mmHg or variance from baseline >30%), this was defined as an anaphylactic reaction disregarding involvement of other organ systems. * NIAID - National Institute of Allergy and Infectious Diseases FAAN - Food Allergy and Anaphylaxis Network | Within 24 hours of each study drug infusion: on Day 1 and Day 14 | 
| Number of Patients Experiencing Hypersensitivity Reactions | The standardized MedDRA query (SMQ) - Hypersensitivity reactions (SMQ 20000214) was used for the identification of hypersensitivity reactions overall from first infusion in the adverse event database. | 24 weeks study duration | 
| Immunogenicity | Number of patients tested positive for anti-drug-antibodies (ADA) post-randomization. Patients with negative ADA results at screening and at least one evaluable post-randomization ADA assessment are included in the analysis | 24 weeks study duration | 
| Number of Patients Experiencing Potential Infusion-Related Reactions | Patients, experienced infusion related reactions repeatedly (i.e. during the first and second infusion) are counted only once in the overall line. | On the day of and on the day after each study drug infusion (e.g. on study day 1 and 2 for the 1st study drug infusion and on study day 14 and 15 for the 2nd study drug infusion, if the second drug infusion was given on study day 14) |