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NCT01682512

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

Terminated Phase 3 Results posted Last updated 30 January 2018
What this trial tests

Phase 3 trial testing BI 695500 in Arthritis, Rheumatoid in 294 participants. Terminated before completion.

Timeline
5 September 2012
Primary endpoint
17 November 2015
12 October 2016

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment294
Start date5 September 2012
Primary completion17 November 2015
Estimated completion12 October 2016
Sites110 locations across Netherlands, Greece, Ukraine, Belgium, Chile, Ireland, United Kingdom, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 18 to 80, any sex, with Arthritis, Rheumatoid. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I Primary · 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 imp

GroupValue95% CI
BI 695500-1.8-2.08 – -1.50
Rituxan®-1.4-1.64 – -1.09
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) Primary · 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

GroupValue95% CI
BI 695500171000± 41.1
Rituxan®167000± 40.5
MabThera®193000± 37.9
PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages) Primary · 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.

GroupValue95% CI
BI 695500174000± 42.2
Rituxan®169000± 42.0
MabThera®202000± 35.3
PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours) Primary · 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.

GroupValue95% CI
BI 69550049800± 40.1
Rituxan®51900± 28.9
MabThera®55600± 30.7
PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose) Primary · 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.

GroupValue95% CI
BI 695500434± 31.1
Rituxan®462± 32.0
MabThera®486± 28.1
Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II Secondary · 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 c

GroupValue95% CI
BI 69550026.6
Rituxan®23.3
MabThera®56.3
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) Secondary · 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

GroupValue95% CI
BI 695500165000± 42.9
Rituxan®158000± 50.0
MabThera®180000± 40.6

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study medication and prior to the last date of study medication plus 6 months (180 days); up to 48 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BI 695500
Serious: 9/116 (8%)
Deaths:
Rituxan®
Serious: 9/110 (8%)
Deaths:
MabThera®
Serious: 5/65 (8%)
Deaths:

Serious adverse events (31 terms)

ReactionSystemBI 695500Rituxan®MabThera®
Anaphylactic reactionImmune system disorders
Hypertensive crisisVascular disorders
LeukopeniaBlood and lymphatic system disorders
Ischaemic cardiomyopathyCardiac disorders
Pericardial effusionCardiac disorders
CholelithiasisHepatobiliary disorders
Anaphylactoid reactionImmune system disorders
Abscess neckInfections and infestations
DiverticulitisInfections and infestations
Gastroenteritis viralInfections and infestations
PneumoniaInfections and infestations
Pseudomonal sepsisInfections and infestations
Pyelonephritis acuteInfections and infestations
SepsisInfections and infestations
Septic shockInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
FallInjury, poisoning and procedural complications
Femoral neck fractureInjury, poisoning and procedural complications
Fibula fractureInjury, poisoning and procedural complications
Hip fractureInjury, poisoning and procedural complications
Joint injuryInjury, poisoning and procedural complications
Multiple fracturesInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
Tibia fractureInjury, poisoning and procedural complications
Intervertebral disc degenerationMusculoskeletal and connective tissue disorders
Other adverse events (6 terms — click to expand)

ReactionSystemBI 695500Rituxan®MabThera®
Viral upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
DiarrhoeaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Anaphylactic reaction, Hypertensive crisis, Leukopenia, Ischaemic cardiomyopathy, Pericardial effusion, Cholelithiasis, Anaphylactoid reaction, Abscess neck.

Data from ClinicalTrials.gov NCT01682512 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis.
    Singh JA, Hossain A, Mudano AS, Tanjong Ghogomu E, et al · · 2017 · cited 44× · PMID 28481462 · DOI 10.1002/14651858.cd012657
  2. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.
    Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, et al · · 2017 · cited 38× · PMID 28282491 · DOI 10.1002/14651858.cd012591

Verify or expand the search:

Other trials of BI 695500

Trials testing the same drug.

Other recruiting trials for Arthritis, Rheumatoid

Currently open trials in the same condition.

Other Boehringer Ingelheim trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing