Clinical trial NCT06175338: Study, Evaluating Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety Profiles of Rituximab Compared to MabThera® in Patients With Rheumatoid Arthritis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Mabscale, LLC
Sponsor class: INDUSTRY
First posted: 2023-12-18
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AUC(w2-24)
timeFrame: Day 1 to Week 24
measure: AUC0-inf
timeFrame: Day 1 to Week 24
measure: Cmax
timeFrame: Dose 2 to the end of the study or Week 24
Secondary outcomes:
measure: Ctrough
timeFrame: Day 1 to Day 15
measure: AUC0-d15
timeFrame: Day 1 - Day 15 (before infusion)
measure: AUC0-w12
timeFrame: Day 1 - Week 12 (before infusion)
measure: AUCd15-n24
timeFrame: Day 15 - Week 24
Other outcomes:
Locations:
city: Kaliningrad
country: Russian Federation
facility: Immanuel Kant Baltic Federal University
city: Kazan
country: Russian Federation
facility: Scientific-Research Medical Complex Your Health
city: Kemerovo
country: Russian Federation
facility: LLC "Medical Center Revma-Med"
city: Korolev
country: Russian Federation
facility: LLC "Korolev Family Clinic №4"
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital №1
city: Moscow
country: Russian Federation
facility: V.A. Nasonova Research Institute of Rheumatology
city: Orenburg
country: Russian Federation
facility: Orenburg State Medical University
city: Saint-Petersburg
country: Russian Federation
facility: JSC "Northwestern Center for Evidence-Based Medicine"
city: Saint-Petersburg
country: Russian Federation
facility: LLC "Interleukin"
city: Saint-Petersburg
country: Russian Federation
facility: Medical center "Capital-Polis"
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Vladimir
country: Russian Federation
facility: LLC "Biomed"
Study officials:
References: