Efficacy, Pharmacokinetics, and Safety of BI 695500 in Patients With Rheumatoid Arthritis

Phase 3

Terminated

• Conditions: Arthritis, Rheumatoid
• Interventions: Drug: BI 695500; Drug: Rituxan®; Drug: MabThera®

• Registration Number: NCT01682512
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The primary objectives of this trial are (1) To show PK (Pharmacokinetic) similarity of BI 695500 to rituximab. (2)To establish statistical equivalence of efficacy of BI 695500 and rituximab, in patients with moderately to severely active RA (Rheumatoid Arthritis), based on the change in Disease Activity Score 28 (DAS28) score measured at 24 weeks compared to Baseline and the American College of Rheumatology 20% (ACR20) response rate at Week 24.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-08-10
• Study Start: 2012-09-05
• Study First Submitted QC: 2012-09-10
• Study First Posted: 2012-09-11
• Primary Completion: 2015-11-17
• Study Completion: 2016-10-12
• Results First Submitted: 2017-10-24
• Status Verified: 2018-01
• Results First Submitted QC: 2018-01-04
• Last Update Submitted: 2018-01-04
• Results First Posted: 2018-01-30
• Last Update Posted: 2018-01-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 294

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part I BI 695500 group	BI 695500	BI 695500, Two infusions separated by 2 weeks, Intravenous infusion
Part I Rituxan®	Rituxan®	rituximab, Two infusions separated by 2 weeks, Intravenous infusion
Part I MabThera®	MabThera®	rituximab, Two infusions separated by 2 weeks, Intravenous infusion
Part II BI 695500 group	BI 695500	BI 695500, Two infusions separated by 2 weeks, Intravenous infusion
Part II rituximab group	Rituxan®	rituximab, Two infusions separated by 2 weeks, Intravenous infusion

Primary Outcome Measures

Name	Time	Method
PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)	Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.	PK (Part I only): AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.
PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)	Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.	PK (Part I only): observed Cmax (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.
Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I	Baseline and Week 24	The DAS28 score was derived using the formula: DAS28 (ESR) = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.70\*ln(ESR) + 0.014\*(GH), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the General Health component of the DAS \[score on a visual analogue scale (VAS) ranging from 0 (very well) to 100 (very poor)\].; DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Low disease activity is defined as a DAS28 score of ≤ 3.2 and DAS28 remission is defined as a DAS28 score of \< 2.6. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2.; The full analysis set (FAS) contained all randomized subjects who received at least one dose of trial medication, had at least one assessment of primary efficacy endpoint at Baseline and at post-baseline visit prior or at Week 24 visit.
PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)	Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.	Pharmacokinetic (PK) (Part I only): AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. As per protocol all the following criteria had to be fulfilled for a patient to be defined as PK evaluable for the Pharmacokinetic analysis set (PKS): Full first and second dose given. Pre-dose concentration available prior to the second dose. Ability to estimate AUC during the infusion phases. Ability to estimate the AUC for the distribution phase after the second dose. Ability to estimate the terminal half-life (t1/2) after the second dose.; gMean - Geometric Mean
PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)	Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.	PK (Part I only): AUC0-inf pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages, and extrapolated to infinity using predicted last observed quantifiable concentration). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.

Secondary Outcome Measures

Name	Time	Method
PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)	Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.	PK (Part I only): AUC0-inf, ppk. Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. A modeling approach was used to impute missing values as well as impute missing concentrations after the first dose with a sampling schedule identical to the first 2 weeks after the second dose. A unit dose of 1000 mg was used in calculating the imputed values. The resulting dataset thus consisted of PK evaluable and PK non-evaluable patients with both measured as well as imputed concentration values. The prediction of these concentrations was based on a mixed effect modeling approach and included significant covariates as identified during the PK model development (including age, body surface area \[BSA\], body mass index \[BMI\], weight, gender, race, and formulation).
Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II	Week 24	A subject has an ACR20 response if all of the following occur: * a \> 20% improvement in the swollen joint count (66 joints); * a \> 20% improvement in the tender joint count (68 joints); * a \> 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (C-reactive protein).; The percentage of subjects meeting the ACR20 response criteria at Week 24 (part-I and II) is presented for subjects randomised to receive BI 695500, Rituxan and MabThera.

Trial Locations

Locations (107)

Rheumatology Associates; 🇺🇸 Birmingham, Alabama, United States

Achieve Clinical Research, LLC; 🇺🇸 Birmingham, Alabama, United States

Arizona Arthritis & Rheumatology Associates, P.C.; 🇺🇸 Glendale, Arizona, United States

Arizona Arthritis and Rheumatology Research, PLLC; 🇺🇸 Phoenix, Arizona, United States

Little Rock Diagnostic Clinic; 🇺🇸 Little Rock, Arkansas, United States

Medvin Clinical Research; 🇺🇸 Covina, California, United States

TriWest Research Associates, LLC; 🇺🇸 El Cajon, California, United States

Advanced Medical Research, LLC; 🇺🇸 Lakewood, California, United States

Premiere Clinical Research, LLC; 🇺🇸 Lakewood, California, United States

ProHealth Partners; 🇺🇸 Long Beach, California, United States

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