Efficacy, pharmacokinetics, and safety of BI 695500 versus rituximab in patients with moderately to severely active rheumatoid arthritis: a randomized, double-blind, parallel arm, multiple dose, active comparator trial.

Efficacy, pharmacokinetics, and safety of BI 695500 versus rituximab in patients with moderately to severely active rheumatoid arthritis: a randomized, double-blind, parallel arm, multiple dose, active comparator trial. - Bio-sequetia RA study

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON41649

Enrollment

Registered

2011-12-13

Start date

2013-08-27

Completion date

Unknown

Last updated

2024-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

rheuma rheumatoid arthritis

Interventions

Part I (Phase 1 study) contains three groups: 1) 50 patients receiving BI 695500. each patient will receive two 1000 mg intravenous (IV) drug infusions: the first on day 1 and the second on Day 15.

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Adult patients, between 18 and 80 years of age, with moderately to severely active RA for at least 6 months as defined by at least six swollen joints (66 joint count) and at least eight tender joints (68 joint count) at Screening and Baseline (Day 1), and either an erythrocyte sedimentation rate (ESR) of > 28 mm/hour OR a C-reactive protein (CRP) level > 1.0 mg/dL (normal:

Exclusion criteria

Exclusion criteria: Patients with active infection, severe immunosuppression or severe heart failure will be excluded (for all exclusion criteria see page 36-38 of the protocol).

Design outcomes

Primary

Measure	Time frame
PK (Part I only): AUC0-tz, AUC0-*. pred (determined after the second drug infusion) Efficacy co-primary endpoints: Change in DAS28 (ESR) from Baseline to Week 24.	—

Secondary

Measure	Time frame
• PK (part I only): AUC 0-336 (dertermined after the first drug infusion) and observed Cmax (determined after the second drug infusion). • The proportion of patients meeting American College of Rheumatology 20 response criteria at Week 48; • American College of Rheumatology 50% and American College of Rheumatology 70% responders at Weeks 24 and 48; • The proportion of patients who meet the ACR/EULAR definition of remission at Weeks 24 and 48. • The change from Baseline in DAS28 (CRP) at Week 24 and Week 48; • The change from Baseline in DAS28 (ESR) at Week 48 • European League Against Rheumatism response at Weeks 24 and 48; • Individual parameters of the ACR improvement criteria: swollen joint count, tender joint count, patients and physicians global assessments of disease activity, patients assessment of pain, HAQ-DI and acute phase reactant (CRP) at Weeks 24 and 48; • The change from Baseline in 36-item Short Form Health Survey at Weeks 24 and 48; • Immunogenicity (proportion of patients with ADAs) at Weeks 24 and 48; ACR20 responsor rate at Week 24. Other PK endpoints: • Part I only: time from dosing to maximum measured concentration (tmax), area under the plasma concentration versus time curve from time zero to infinity extrapolated from observed Clast (AUC0-_obs), the percentage of the AUC0- that is obtained by extrapolation (%AUCtz-_pred and obs), terminal rate constant in plasma (z), terminal elimination half-life of the analyte in plasma (t1/2), all determined after the second drug infusion, as well as total clearance of the analyte in plasma following intravascular administration (CL) and apparent volume of distribution (Vz) during the terminal phase *z following an intravascular dose, all determined after the second drug infusion determined based on the complete exposure. If feasible, further PK endpoints will be derived, such as AUC0-t. Timepoints at which ADA development has a clear impact on PK will be excluded.	—

Measure

Time frame

• PK (part I only): AUC 0-336 (dertermined after the first drug infusion) and observed Cmax (determined after the second drug infusion). • The proportion of patients meeting American College of Rheumatology 20 response criteria at Week 48; • American College of Rheumatology 50% and American College of Rheumatology 70% responders at Weeks 24 and 48; • The proportion of patients who meet the ACR/EULAR definition of remission at Weeks 24 and 48. • The change from Baseline in DAS28 (CRP) at Week 24 and Week 48; • The change from Baseline in DAS28 (ESR) at Week 48 • European League Against Rheumatism response at Weeks 24 and 48; • Individual parameters of the ACR improvement criteria: swollen joint count, tender joint count, patient*s and physician*s global assessments of disease activity, patient*s assessment of pain, HAQ-DI and acute phase reactant (CRP) at Weeks 24 and 48; • The change from Baseline in 36-item Short Form Health Survey at Weeks 24 and 48; • Immunogenicity (proportion of patients with ADAs) at Weeks 24 and 48; * ACR20 responsor rate at Week 24. Other PK endpoints: • Part I only: time from dosing to maximum measured concentration (tmax), area under the plasma concentration versus time curve from time zero to infinity extrapolated from observed Clast (AUC0-*_obs), the percentage of the AUC0-* that is obtained by extrapolation (%AUCtz-*_pred and obs), terminal rate constant in plasma (*z), terminal elimination half-life of the analyte in plasma (t1/2), all determined after the second drug infusion, as well as total clearance of the analyte in plasma following intravascular administration (CL) and apparent volume of distribution (Vz) during the terminal phase *z following an intravascular dose, all determined after the second drug infusion determined based on the complete exposure. If feasible, further PK endpoints will be derived, such as AUC0-t. Timepoints at which ADA development has a clear impact on PK will be excluded.

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)