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NCT01950273

Pharmacokinetics and Pharmacodynamics of BI 695500 vs. Rituximab as First Line-treatment in Patients With Low Tumor Burden Follicular Lymphoma

Completed Phase 1 Results posted Last updated 5 September 2018
What this trial tests

Phase 1 trial testing BI 695500 in Lymphoma, Follicular in 95 participants. Completed in 22 December 2015.

Timeline
27 September 2013
Primary endpoint
22 December 2015
22 December 2015

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment95
Start date27 September 2013
Primary completion22 December 2015
Estimated completion22 December 2015
Sites29 locations across France, New Zealand, Russia, Greece, Belgium, Austria, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Lymphoma, Follicular. 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.

Area Under the Concentration (AUC) Time Curve of BI 695500 and Rituximab (MabThera®) Over the First Dosing Interval (Pre-infusion on Day 1 to Pre-infusion on Day 8) Primary · Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 1, and at 24, 48, 72, 96 and 168 hours from start of infusion 1.

This outcome measure presents area under the concentration time curve of BI 695500 and Rituximab (MabThera®) over the first dosing interval (pre-infusion on Day 1 to pre-infusion on Day 8) (AUCDay 1-Day 8) for assessment of PK (Pharmacokinetics) similarity.

GroupValue95% CI
BI 69550015700± 69.8
Rituximab (MabThera®)17600± 27.9
AUC of BI 695500 and Rituximab (MabThera®) Over the Fourth Dosing Interval (Pre-infusion on Day 22 to Day 29) (AUC Day 22-Day 29) Secondary · Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 4, and at 24, 48, 72, 96 and 168 hours from start of infusion 4.

This outcome measure presents area under the concentration of BI 695500 and Rituximab (MabThera®) over the fourth dosing interval (pre-infusion on Day 22 to Day 29).

GroupValue95% CI
BI 69550041700± 32.3
Rituximab (MabThera®)44300± 24.8
Maximum Measured Concentration of BI 695500 and Rituximab (MabThera®) in Plasma (Cmax) Following Dose 1 Secondary · Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 1, and at 24, 48, 72, 96 and 168 hours from start of infusion 1.

This outcome measure presents maximum measured concentration of BI 695500 and Rituximab (MabThera®) in plasma (Cmax) following Dose 1

GroupValue95% CI
BI 695500207.882± 58.5
Rituximab (MabThera®)228.802± 25.0
Maximum Measured Concentration of Rituximab (MabThera®) and BI 695500 in Plasma (Cmax) Following Dose 4 Secondary · Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 4, and at 24, 48, 72, 96, 168, 336, 672, 1344, 2016 and 2880 hours from start of infusion 4.

This outcome measure presents maximum measured concentration of Rituximab (MabThera®) and BI 695500 in plasma (Cmax) following Dose 4.

GroupValue95% CI
BI 695500397.080± 23.1
Rituximab (MabThera®)412.190± 18.1
Area Under the Depletion-time Curve of the Cluster of Differentiation (CD)19+ B-cell Count (% Change From Baseline (CFB)) in Peripheral Blood From Pre-infusion on Day 1 Until Last Measurement on Day 8 (Pre-infusion) Secondary · Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion, and at 24, 48, 72, 96 and 168 hours from start of infusion.

This outcome measure presents area under the depletion-time curve of the CD19+ B-cell count (% change from baseline) in peripheral blood from pre-infusion on Day 1 until last measurement on Day 8 (pre-infusion) (AUC Day 1-Day 8, CD19+).

GroupValue95% CI
BI 695500-16895.2± 1016.9
Rituximab (MabThera®)-17064.4± 1403.2
Change From Baseline (%) of CD19+ B-cells in Peripheral Blood Measured After Seven Days on Day 8 (Day 8 Pre-infusion Time Point) Secondary · Blood sampling was done at 168 hours from start of infusion.

This outcome measure presents percent change from baseline of CD19+ B-cells in peripheral blood, measured after 7 days (i.e., Day 8 pre-infusion time point) (PCFBpre,2 CD19+).

GroupValue95% CI
BI 695500-99.2± 1.7
Rituximab (MabThera®)-98.8± 4.2
Overall Response Rate (ORR) (Complete Response (CR) Plus Partial Response (PR)) Evaluated Approximately One Month After Last Dose of BI 695500 or Rituximab (MabThera®) Secondary · at Day 50.

Overall Response Rate (ORR) comprised Complete Response (CR) plus Partial Response (PR) evaluated approximately one month after last dose of BI 695500 or Rituximab \[MabThera®\]. Overall Response as defined by the revised International Working Group (IWG) Criteria 2007, using the Investigator's assessment.

GroupValue95% CI
BI 69550044.9
Rituximab (MabThera®)54.3
Percentage of Patients With Treatment Emergent Adverse Events (TEAEs) Selected for Comparability Assessment of BI 695500 and Rituximab (MabThera®) Secondary · Adverse Events (AEs) that started or worsened on or after the first dose of study medication and prior to the last date of study medication + 4 months (120 days) inclusive.

This outcome measure presents percentage of patients with Treatment Emergent Adverse Events (TEAEs) selected for comparability assessment of BI 695500 and Rituximab (MabThera®).

GroupValue95% CI
BI 69550036.7
Rituximab (MabThera®)34.8

Adverse events — posted to ClinicalTrials.gov

Time frame: From first drug administration until 142 days after last drug administration, up to 156 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BI 695500
Serious: 4/49 (8%)
Deaths:
Rituximab (MabThera®)
Serious: 3/46 (7%)
Deaths:

Serious adverse events (8 terms)

ReactionSystemBI 695500Rituximab (MabThera®)
VertigoEar and labyrinth disorders
GoitreEndocrine disorders
Anaphylactoid reactionImmune system disorders
Back painMusculoskeletal and connective tissue disorders
Confusional statePsychiatric disorders
Acute kidney injuryRenal and urinary disorders
HaemothoraxRespiratory, thoracic and mediastinal disorders
Abortion inducedSurgical and medical procedures
Other adverse events (21 terms — click to expand)

ReactionSystemBI 695500Rituximab (MabThera®)
NauseaGastrointestinal disorders
HeadacheNervous system disorders
PruritusSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
Alanine aminotransferase increasedInvestigations
FatigueGeneral disorders
Gamma-glutamyltransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
ThrombocytopeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Blood cholesterol increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
ErythemaSkin and subcutaneous tissue disorders

Most-reported serious reactions: Vertigo, Goitre, Anaphylactoid reaction, Back pain, Confusional state, Acute kidney injury, Haemothorax, Abortion induced.

Data from ClinicalTrials.gov NCT01950273 adverse events section.

Sponsor's own description

The primary objective of the study is to assess the pharmacokinetic (PK) similarity of Boehringer Ingelheim (BI) 695500 vs. rituximab (MabThera®) in previously untreated patients with low tumor burden follicular lymphoma (LTBFL). The secondary objective of the study is to evaluate the pharmacodynamics (PD), safety, and anti-tumor activity of BI 695500 vs. rituximab (MabThera®), as well as the presence of anti-drug antibodies (ADAs).

Publications & conference data

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

  1. Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma.
    Coleman M, Lammers PE, Ciceri F, Jacobs IA. · · 2016 · cited 22× · PMID 26906106 · DOI 10.1016/j.clml.2016.01.004
  2. Rituximab in the treatment of follicular lymphoma: the future of biosimilars in the evolving therapeutic landscape.
    Subramanian J, Cavenagh J, Desai B, Jacobs I. · · 2017 · cited 16× · PMID 28479860 · DOI 10.2147/cmar.s120589
  3. The Role of Rituximab in Chronic Lymphocytic Leukemia Treatment and the Potential Utility of Biosimilars.
    Brown JR, Cymbalista F, Sharman J, Jacobs I, et al · · 2018 · cited 10× · PMID 29212732 · DOI 10.1634/theoncologist.2017-0150

Verify or expand the search:

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Trials by the same sponsor.

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