Phase 2
Completed N=220
A Pharmacokinetic/Pharmacodynamic Study Comparing PF-05280586 To Rituximab In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To TNF Inhibitors (REFLECTIONS B328-01)
Source: ClinicalTrials.gov NCT01526057 ↗Enrolled (actual)
220
Serious AEs
4.6%
Results posted
Nov 2019
Primary outcomePrimary: Maximum Serum Concentration (Cmax) of Rituximab — 453; 422; 430 micrograms per milliliter
Summary
In this study, patients with moderate to severe rheumatoid arthritis who are being treated with methotrexate will receive 2 intravenous treatments with either PF-05280586 or Rituxan (Rituximab) or MabThera (Rituximab). During the course of the study, the effects of the drugs will be assessed by sampling the levels of drug in the blood, blood cell counts, and by comparing these levels among the different treatments. Safety, tolerability and immunologic response also will be evaluated throughout.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Serum Concentration (Cmax) of Rituximab |
453; 422; 430 | — |
| PRIMARY AUC 0-inf of Rituximab |
213000; 200000; 214000 | — |
| SECONDARY Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) |
52100; 49600; 49200 | — |
| SECONDARY Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) |
198000; 188000; 196000 | — |
| SECONDARY CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) |
13312; 14304; 12496 | — |
| SECONDARY Minimum Post-Baseline CD19+ B-cell Count (/uL) |
0.0; 0.0; 0.0 | — |
| SECONDARY Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) |
1.4; 1.6; 1.5 | — |
| SECONDARY Duration of B-cell Depletion (τB-cell) (Days) |
126; 123; 120 | — |
| SECONDARY Percentage of Participants With CD19+ B-cell Count Recovery |
4.4; 8.7; 9.0 | — |
| SECONDARY Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell) |
13312.1; 14304.2; 12495.9 | — |
| SECONDARY Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) |
1.381; 1.460; 1.394; 0.0; 0.0; -0.0 | — |
| SECONDARY Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) |
3.3; 1.4; -0.5; 0.1; -0.3; 0.7 | — |
| SECONDARY Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit |
34.2; 33.8; 32.9; 54.8; 56.8; 42.5 | — |
| SECONDARY Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit |
2.7; 2.7; 2.7; 6.8; 6.8; 8.2 | — |
| SECONDARY Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit |
8.2; 5.4; 9.6; 19.2; 16.2; 20.5 | — |
| SECONDARY Percentage of Participants by Anti-drug Antibody (ADA) Status |
9.6; 13.5; 12.3 | — |
| SECONDARY Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit |
0.0; 0.0; 0.0 | — |
| SECONDARY Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) |
5.6862; 5.7928; 6.2221; -0.9; -0.8; -1.1 | — |
| SECONDARY Percent Change From Baseline in DAS28-CRP by Visit |
-16.1; -13.6; -18.6; -25.4; -24.0; -26.0 | — |
| SECONDARY Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit |
14.5; 10.8; 8.7; 22.5; 22.5; 19.4 | — |
| SECONDARY Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit |
33.3; 35.1; 42.0; 47.9; 39.4; 43.3 | — |
| SECONDARY Percentage of Participants With No EULAR Response Based on DAS28 by Visit |
52.2; 54.1; 49.3; 29.6; 38.0; 37.3 | — |
| SECONDARY Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit |
14.5; 10.8; 10.1; 23.9; 25.4; 19.4 | — |
| SECONDARY Percentage of Participants With DAS Remission (DAS <2.6) by Visit |
8.7; 4.1; 7.2; 16.9; 8.5; 11.9 | — |
| SECONDARY Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit |
1.6541; 1.5929; 1.7466; -0.2; -0.2; -0.2 | — |
| SECONDARY Percent Change From Baseline in HAQ-DI Score by Visit |
-10.4; -13.2; -9.0; -15.1; -23.5; -14.8 | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed diagnosis of rheumatoid arthritis
- Meets Class I, II or III of the ACR 1991 Revised Criteria
- RA seropositivity
- Stable dose of methotrexate
- Inadequate response to TNF inhibitors
Exclusion Criteria
- Any prior treatment with lymphocyte depleting therapies
- History of active TB infection
- Known or screen test positive for specific viruses or indicators of viral infection
Data sourced from ClinicalTrials.gov (NCT01526057). 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.