Phase 2
Completed N=276
Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT02296775 ↗
Enrolled (actual)
276
Serious AEs
6.5%
Results posted
Jan 2020
Primary outcomePrimary: Area Under the Concentration-Time Curve From Time 0 to 336 Hours (AUC0-336) Post First Dose — 49000; 49000; 51400 ug*h/ml
Summary
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-Time Curve From Time 0 to 336 Hours (AUC0-336) Post First Dose |
49000; 49000; 51400 | — |
| PRIMARY AUC0-∞ Over the Entire Course of Therapy (2 Doses) From Day 1 Through Week 16. |
189000; 189000; 201000 | — |
| PRIMARY Area Under Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) (Second Dose). |
139000; 137000; 146000 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) After First Dose |
405.452; 388.017; 405.200 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) After Second Dose |
490.182; 470.237; 478.149 | — |
| SECONDARY Time to Cmax (Tmax) After First Dose. |
5.25; 5.25; 5.25 | — |
| SECONDARY Time to Cmax (Tmax) After Second Dose |
5.25; 5.25; 5.25 | — |
| SECONDARY Volume of Distribution (Vz) |
5.69; 5.76; 5.55 | — |
| SECONDARY Systemic Clearance (CL) |
0.254; 0.254; 0.238 | — |
| SECONDARY Terminal Half-life (t1/2) |
374; 378; 391 | — |
| SECONDARY Mean Change in Disease Activity Score-C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Weeks 4 |
-1.004; -0.871; -0.96 | — |
| SECONDARY Mean Change in DAS28-CRP From Baseline Per Unit Time at 8 Weeks. |
-1.379; -1.192; -1.424 | — |
| SECONDARY Mean Change in DAS28-CRP From Baseline Per Unit Time at Week 12. |
-1.652; 1.443; -1.718 | — |
| SECONDARY Mean Change in Disease Activity Score- C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Week 16. |
-1.892; -1.49; -1.814 | — |
| SECONDARY Percentage of Patients With B-cell Counts 20% Below the Lower Limit of Normal |
98.8; 100; 100 | — |
| SECONDARY Percentage of Patients With Peripheral B-cell Counts Depletion at Week 16. |
10.0; 4.9; 10.1 | — |
| SECONDARY Percentage of Patients With Peripheral B-cell Counts Depletion at Week 24. |
0.0; 3.7; 1.3 | — |
| SECONDARY Percentage of Patients With ACR20 at Week 24 |
72; 69.1; 68.4 | — |
| SECONDARY Percentage of Patients With ACR50 at Week 24 |
43.9; 39.5; 43.0 | — |
| SECONDARY Percentage of Patients With ACR70 Response at Week 24 |
17.1; 14.8; 15.2 | — |
| SECONDARY Change From Baseline in HAQ-DI at Week 24. |
0.742; 0.691; 0.726 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female patients, 18 to 65 years of age
- Diagnosis of RA, according to ACR criteria (1987), of at least 6 months duration
- At randomization, tender joint count ≥ 6 and swollen joint count ≥ 6
- Evidence of at least moderate disease activity
- 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
- Patients must be on a stable dose of folic acid or equivalent (≥5 mg per week)
- Chest X-ray not suggestive of any lung infections including pulmonary tuberculosis (TB)
- Contraception required per protocol
Exclusion Criteria
- 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
- Any clinically relevant abnormality detected on screening history, physical examination, clinical laboratory, chest X-ray, or electrocardiogram (ECG), other than values consistent with RA
- Evidence of active, suspected or inadequately treated TB
- Positive serological test for hepatitis C virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
- History of cardiovascular disease, history of stroke, or uncontrolled hypertension
- History of lymphoproliferative disease or organ allograft
- History of cancer (except for in situ cancer, excised, or limited stage, curatively treated cancer with no sign of disease for >5 years)
- History of allergy (medication history) to any of the compounds used in the study
- Pregnant or lactating women or women planning to become pregnant during the study
Data sourced from ClinicalTrials.gov (NCT02296775). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.