Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis

Dr.Reddy's Laboratories

Status and phase: Completed; Phase 2; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Biological: Rituxan; Biological: DRL_RI; Biological: MabThera

Study type: Interventional

Funder types: Industry

Identifiers

NCT02296775

RI-01-003

Details and patient eligibility

About

This study will compare the plasma pharmacokinetic profile and the change in disease activity score in patients with active rheumatoid arthritis following treatment with two 1000 mg doses of DRL_RI or one of two sources of rituximab (Rituxan® or MabThera®). Patients will also be monitored for safety, B cell depletion and recovery, and for the development of immune responses to the administered study drugs

Enrollment: 276 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female patients, 18 to 65 years of age
2. Diagnosis of RA, according to ACR criteria (1987), of at least 6 months duration
3. At randomization, tender joint count ≥ 6 and swollen joint count ≥ 6
4. Evidence of at least moderate disease activity
5. Patients receiving oral or parenteral MTX with a dose of 15 to 25 mg per week when given alone or 10 to 25 mg per week in combination with additional non-biologic DMARD(s) for at least 6 months and on stable dose for at least 3 months
6. Patients must be on a stable dose of folic acid or equivalent (≥5 mg per week)
7. Chest X-ray not suggestive of any lung infections including pulmonary tuberculosis (TB)
8. Contraception required per protocol

Exclusion criteria

1. Prior therapy with

   • Rituximab, abatacept, tocilizumab, anakinra or an agent/antibody targeting CD20, CD19 or B cells
   • Tumor necrosis factor (TNF) alfa antagonists or other biologic DMARDs

   Other prior or concurrent therapies may also be excluded

2. Any clinically relevant abnormality detected on screening history, physical examination, clinical laboratory, chest X-ray, or electrocardiogram (ECG), other than values consistent with RA

3. Evidence of active, suspected or inadequately treated TB

4. Positive serological test for hepatitis C virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus

5. History of cardiovascular disease, history of stroke, or uncontrolled hypertension

6. History of lymphoproliferative disease or organ allograft

7. History of cancer (except for in situ cancer, excised, or limited stage, curatively treated cancer with no sign of disease for >5 years)

8. History of allergy (medication history) to any of the compounds used in the study

9. Pregnant or lactating women or women planning to become pregnant during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

276 participants in 3 patient groups

DRL_RI

Experimental group

Treatment:

Biological: DRL_RI

Rituxan

Active Comparator group

Treatment:

Biological: Rituxan

MabThera

Active Comparator group

Treatment:

Biological: MabThera