Study, Evaluating Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety Profiles of Rituximab Compared to MabThera® in Patients With Rheumatoid Arthritis

June 5, 2024 updated by: Mabscale, LLC

Randomized Double Blind Phase I Trial Comparing Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety of Rituximab (Mabscale LLC, Russia)+ Methotrexate+ Folic Acid and MabThera® Methotrexate+ Folic Acid in Adult Patients With Moderate or Severe Rheumatoid Arthritis With Insufficient Response to Treatment Tumor Necrosis Factor (TNF-α)

A randomised, double blind, parallel group, multicentre study to compare the pharmacokinetics, pharmacodynamics, immunogenicity and safety of Rituximab (Mabscale LLC, Russia) versus MabThera® in patients with rheumatoid arthritis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

RIT-1/01092021 is a double-blind randomized, parallel group, multicenter clinical trial comparing pharmacokinetics, pharmacodynamics, immunogenicity and safety of Rituximab (Mabscale LLC, Russia) and MabThera® in adult patients with moderate or severe rheumatoid arthritis with insufficient response to treatment tumor necrosis factor (TNF-α) inhibitors receiving background treatment with methotrexate. The purpose of the study is to demonstrate equivalence of pharmacokinetics, pharmacodynamics, immunogenicity and safety of Rituximab (Mabscale LLC, Russia) and MabThera®. The study will take place across approximately 30 study sites in Russia in order to randomize 208 patients. Rituximab is a monoclonal antibody currently being developed by Mabscale LLC, as a proposed biosimilar to MabThera®, which is approved as treatment in case of insufficient response or toxicity to treatment tumor necrosis factor (TNF-α) inhibitors receiving background treatment with methotrexate. This randomized equivalence study is designed to meet the regulatory requirement for approval of a biosimilar product.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
208

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Russian Federation
      • Kaliningrad, Russian Federation
        • Immanuel Kant Baltic Federal University
      • Kazan, Russian Federation
        • Scientific-Research Medical Complex Your Health
      • Kemerovo, Russian Federation
        • LLC "Medical Center Revma-Med"
      • Korolev, Russian Federation
        • LLC "Korolev Family Clinic №4"
      • Moscow, Russian Federation
        • Moscow City Clinical Hospital №1
      • Moscow, Russian Federation
        • V.A. Nasonova Research Institute of Rheumatology
      • Orenburg, Russian Federation
        • Orenburg State Medical University
      • Saint-Petersburg, Russian Federation
        • JSC "Northwestern Center for Evidence-Based Medicine"
      • Saint-Petersburg, Russian Federation
        • LLC "Interleukin"
      • Saint-Petersburg, Russian Federation
        • Medical center "Capital-Polis"
      • Saratov, Russian Federation
        • Saratov State Medical University
      • Vladimir, Russian Federation
        • LLC "Biomed"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male and Female 18-65 y.o. with body weight 50-120 kg
  • Patients with active rheumatoid arthritis with disease duration minimum 6 months prior to screening visit per ACR/EULAR 2019 criteria classification.

  • Moderate or severe active course of rheumatoid arthritis, which is defined as the fulfillment of all of the following conditions:

    • ≥6 tender joints (based on a score of 68 joints) at screening and baseline; And
    • ≥6 swollen joints (based on a score of 66 joints) at screening and at baseline; And
    • level of C-reactive protein is not less than 10 mg/l or ESR is not less than 28 mm/hour at screening.
  • Positive result of the analysis for antibodies to cyclic citrullinated peptide (≥10 units/ml) and / or the presence of rheumatoid factor (≥ 20 units/ml) at screening (see section).
  • Received treatment for RA and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy;
  • Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose 10-25 mg/week;

Exclusion Criteria:

  • Contraindications according to the MabThera SmPC and every serious coexisting diseases which, in the Investigator's opinion, would preclude subject participation
  • History of current rheumatic autoimmune disease other than RA and current inflammatory joint disease other than RA
  • Positive tests for HIV, hepatitis B surface antigen (HBsAg) Anti-HBc antibody, hepatitis C antibody
  • Prior treatment with rituximab, other anti-CD20 mAb
  • Pregnancy or lactation or women planning to get pregnant during the course of the study and/or within 12 months post last study drug infusion
  • COVID prior 8 weeks prior to Screening visit or other acute systemic infection within 4 weeks prior to Day 1
  • Allergic reaction or intolerance to rituximab, MabionCD20 or any of their components
  • Severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or previous treatment of any lymphocyte-depleting therapies
  • Confirmed current active tuberculosis (TB).
  • Any significant cardiac disease
  • History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a murine product.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rituximab (manufactured by Mabscale, LLC)
Eligible subjects (104 patients) will receive Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml) twice: on Visit 1 and 5. The following visits are the visits of safety and PK, PD and immunogenicity and also preliminary effectiveness). Patients will also receive background treatment Methotrexate+ Folic acid.
Drug: Rituximab
Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)
Active Comparator: MabThera®
Eligible subjects (104 patients) will receive MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml) twice: on Visit 1 and 5. The following visits are the visits of safety and PK, PD and immunogenicity and also preliminary effectiveness). Patients will also receive background treatment Methotrexate+ Folic acid.
Drug: MabThera®
MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
AUC(w2-24)
Time Frame: Day 1 to Week 24
Area Under the Concentration Time Curve predose Day 1 to Week 24 (AUC(w2-24).
Day 1 to Week 24
AUC0-inf
Time Frame: Day 1 to Week 24
Area Under the Concentration Time Curve extrapolated from 0 to infinity (AUC0-inf)
Day 1 to Week 24
Cmax
Time Frame: Dose 2 to the end of the study or Week 24
Maximum Plasma Concentration (Cmax) after Dose 2
Dose 2 to the end of the study or Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ctrough
Time Frame: Day 1 to Day 15
Residual concentration (Ctrough) before the second infusion on Day 15
Day 1 to Day 15
AUC0-d15
Time Frame: Day 1 - Day 15 (before infusion)
Area under the concentration-time curve from 0 (directly pre-infusion on Day 1) before pre-infusion measurement on Day 15 (AUC0-d15)
Day 1 - Day 15 (before infusion)
AUC0-w12
Time Frame: Day 1 - Week 12 (before infusion)
Area under the concentration-time curve from 0 and before measurement at Week 12 (AUC0-w12)
Day 1 - Week 12 (before infusion)
AUCd15-n24
Time Frame: Day 15 - Week 24
Area under the concentration-time curve from measurement immediately before the second infusion (Day 15) before measuring in point Week 24 (AUCd15-n24)
Day 15 - Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mabscale, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 14, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 7, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RIT-1/01092021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings