MabionCD20® Compared to MabThera® and Rituxan® in Patients With Rheumatoid Arthritis

NCT04680962 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: MabionCD20-003RA
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary objective of the study is to establish a 3-way PK similarity bridge between MabionCD20 (candidate biosimilar to rituximab), MabThera® (EU-sourced rituximab) and Rituxan® (US-sourced rituximab) following the administration of these drugs to patients with moderate-to-severe rheumatoid arthritis. Main secondary objective is to confirm therapeutic similarity between MabionCD20 and the reference rituximab.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Area Under the Serum Concentration-time Curve from Day 1 to Week 24, with extrapolation to infinity [AUC 0-inf (D1-W24)]

  Concentration of rituximab in serum over the entire PK study duration, with extrapolation to infinity. Outcome based on all PK samples collected in the study - from Day 1 (first infusion) to Week 24 (before administration of the 2nd treatment course).

  Day 1 to Week 24

• Area Under the Serum Concentration-time Curve from Day 1 to Day 15 [AUC 0-t (D1-D15)]

  Concentration of rituximab in serum measured from Day 1 (before the 1st drug infusion) to Day 15 (before the 2nd drug infusion).

  Day 1 to Day 15

Secondary Outcomes (20)

• Mean Change from Baseline in DAS28-ESR score

  Baseline to Week 48

• Mean Change from Baseline in DAS28-CRP score

  Baseline to Week 48

• Percentage of patients achieving an ACR20/50/70 response

  Baseline to Week 48

• Percentage of patients with low disease activity (DAS28-ESR <3.2)

  Baseline to Week 48

• Percentage of patients with disease remission (DAS28-ESR <2.6)

  Baseline to Week 48

Study Arms (3)

MabionCD20 / MabionCD20

EXPERIMENTAL

Patients receive one or two treatment courses of MabionCD20, each consisting of two 1000 mg i.v. infusions at an interval of 14 days. Investigational drug will be administered at Day 1 and Day 15, and, if patient is eligible for re-treatment, also at Week 24 and Week 26.

Biological: MabionCD20 (candidate biosimilar to rituximab)

EU-Rituximab / EU-Rituximab

ACTIVE COMPARATOR

Patients receive one or two treatment courses of MabThera®, each consisting of two 1000 mg i.v. infusions at an interval of 14 days. Investigational drug will be administered at Day 1 and Day 15, and, if patient is eligible for re-treatment, also at Week 24 and Week 26.

Biological: MabThera®

US-Rituximab / MabionCD20

ACTIVE COMPARATOR

Patients receive a single treatment course of Rituxan®, consisting of two 1000 mg i.v. infusions at Day 1 and Day 15. After 24 weeks of follow-up, all patients eligible for re-treatment, are switched to receive a single treatment course of MabionCD20, consisting of two 1000 mg i.v. infusions at Week 24 and Week 26.

Biological: MabionCD20 (candidate biosimilar to rituximab); Biological: Rituxan®

Interventions

MabionCD20 (candidate biosimilar to rituximab) BIOLOGICAL

Intravenous infusion, 10 mg/ml concentrate, 500 ml

Also known as: Rituximab Mabion

MabionCD20 / MabionCD20; US-Rituximab / MabionCD20

MabThera® BIOLOGICAL

Intravenous infusion, 10 mg/ml concentrate, 500 ml

Also known as: EU-Rituximab

EU-Rituximab / EU-Rituximab

Rituxan® BIOLOGICAL

Intravenous infusion, 10 mg/ml concentrate, 500 ml

Also known as: US-Rituximab

US-Rituximab / MabionCD20

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 - 80 years
• Body Surface Area (BSA) between 1.5 and 2.2 m2
• Confirmed diagnosis of RA diagnosed according to the revised (2010) ACR/EULAR classification criteria, with a disease duration minimum of 6 months prior to the Screening Visit
• Currently moderate to severe RA despite ongoing administration of an adequate MTX regimen. Moderate to severe disease is defined here as the presence of the following two criteria:
• Six or more swollen joints and ≥6 tender/painful joints, verified by a physician during the screening and re-confirmed at baseline visit (Day 1)
• DAS28 score ≥3.2 at screening
• No history of treatment with TNF-α inhibitor (innovative or biosimilar, authorized or investigational) at any time before the screening i.e. TNF-α inhibitor naive population.
• Receiving MTX treatment at a dosage of 7.5-25 mg/week for at least 12 weeks prior to screening, with the last 4 weeks at a stable dose, and willing to remain at this dose for the entire study duration
• Male or WOCBP must consent to use highly effective contraception, from the Screening Visit, during the intervention period, and for at least 12 months after the last dose of study intervention
• Female participants must not be pregnant or lactating (negative baseline serum test)

You may not qualify if:

• History of or current inflammatory joint disease other than RA
• History of or current systemic autoimmune disorder
• ACR functional class IV disease
• History of psychiatric disorder that would interfere with normal participation in the study
• Evidence of HBV, HCV, HIV infection
• Evidence of laboratory-confirmed or clinically suspected SARS-CoV-2 infection within 14 days before the study drug administration and a documented positive RT-PCR test within 72 hours before the first infusion or positive antigen test within 24 hours before the first infusion.
• Serious and/or uncontrolled coexisting diseases which are recognized as major contraindications to the administration of rituximab, methotrexate or any of the pre-medication components or as important risk factors for the development of severe or life-threatening SARS-CoV-2 infection or other factors, which in the Investigator's opinion, would preclude patients participation. This category includes severe pulmonary, cardiovascular, neurologic, renal and hepatic diseases, severe and inadequately controlled type 1 or 2 diabetes.
• Recent history or current evidence of bacterial, viral or fungal infection (excluding infections of nailbeds)
• History of or current active tuberculosis, with typical symptoms of M. tuberculosis infection confirmed by positive results of TB screening test or documented diagnosis prior to screening
• Latent tuberculosis, as documented in subject's medical records or shown by a positive or indeterminate QuantiFERON test performed at screening, in absence of typical symptoms of tuberculosis. However, a patient with latent tuberculosis may become eligible for the study if he/she meets the following criteria:
• Patient completed a standard TB prophylaxis prior to the screening and had no active TB or contact with active TB case after completion of the most recent prophylactic regimen OR received at least four weeks of standard TB prophylactic regimen prior to the screening visit and is capable and willing to continue on this regimen while participating in the study.
• Patient has no active TB at the time of screening, which must be confirmed through referral to a TB specialist if \> 1 year has passed since the completion of the last prophylaxis or if the prophylaxis is still being received by the time of screening
• Patient had no positive findings on chest X-ray examination at screening and within three months prior to screening
• History of cancer (solid tumors, hematologic malignancies and other) within 5 years of the screening
• History of significant cytopenia or other disorder of the hematopoietic system

Sponsors & Collaborators

• Mabion SA: lead
• Parexel: collaborator

Related Links

• Sponsor's website

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 23, 2020
• Study Start: August 3, 2023
• Primary Completion: August 3, 2023
• Study Completion: August 3, 2023
• Last Updated: August 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share