BI 695501 Versus Humira in Patients With Active Crohn's Disease: a Trial Comparing Efficacy, Endoscopic Improvement, Safety, and Immunogenicity

BI 695501 Versus Humira® in Patients With Active Crohn's Disease: a Randomized, Double-blind, Multicenter, Parallel Group, Exploratory Trial Comparing Efficacy, Endoscopic Improvement, Safety, and Immunogenicity

Primary Objective:

The primary objective of this trial is to compare the clinical efficacy of BI 695501 with EU-approved Humira® in patients with active Crohn's disease (CD).

Secondary Objectives:

The secondary objectives of this trial are to compare the efficacy and safety of BI 695501 with EU-approved Humira® across the induction and maintenance phases.

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: BI 695501; Drug: HUMIRA

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Gomel, Belarus, 246012
    • Gomel Regional Clinical
  • Minsk, Belarus, 220096
    • City Clinical Hospital # 10
  • Vitebsk, Belarus, 210603
    • Vitebsk Regional Clinical Oncology Dispensary
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinical Centre Sarajevo
• Croatia
  • Osijek, Croatia, 31000
    • Clinical Hospital Osijek
  • Zagreb, Croatia, 10000
    • Polyclinic Bonifarm
• Czechia
  • Brno, Czechia, 63600
    • Vojenska nemocnice Brno
  • Hradec Kralove, Czechia, 50012
    • Hepato-gastroenterologie HK, s.r.o.
  • Olomouc, Czechia, 779 00
    • Gregar s.r.o.
  • Olomouc, Czechia, 77900
    • PreventaMed, s.r.o.
  • Olomouc, Czechia, 779 00
    • CTCenter Mave, s.r.o., Cllinical Trials Center, Olomouc
  • Ostrava-Poruba, Czechia, 708 52
    • University Hospital Ostrava
  • Ostrava-Vitkovice, Czechia, 703 84
    • Vitkovice Hospital
  • Prague, Czechia, 140 00
    • Medicon, a.s.
  • Praha, Czechia, 15000
    • Axon Clinical, s.r.o.
  • Praha 8, Czechia, 27711
    • University Hospital Na Bulovce
  • Pribram, Czechia, 261 01
    • General Hospital Pribram
  • Usti nad Labem, Czechia, 401 13
    • Masaryk Hospital, Internal Department
• Germany
  • Frankfurt, Germany, 60594
    • Crohn Colitis Centrum Rhein Main
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens Evangelismos
  • Heraklion, Crete, Greece, 71110
    • University General Hospital of Heraklion
  • Rhodes, Greece, 85100
    • General Hospital of Rhodes
• Israel
  • Afula, Israel, 18101
    • Haemek Medical Center
  • Holon, Israel, 58100
    • Wolfson Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center, Ein-Karem
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center Tel HaShomer
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
• Poland
  • Bialystok, Poland, 15-765
    • KLIMED Marek Klimkiewicz
  • Bydgoszcz, Poland, 85231
    • NZOZ Centrum Medyczne KERmed
  • Cracow, Poland, 30-363
    • Medical Center Pleiades
  • Kielce, Poland, 25634
    • Polimedica Centrum Badan
  • Knurow, Poland, 44190
    • Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
  • Lodz, Poland, 90-302
    • SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia
  • Nowa Sol, Poland, 67-100
    • Clinic Medical Center; Nowa Sol
  • Poznan, Poland, 61-113
    • Ai Medical Center, private practice, Poznan
  • Rzeszow, Poland, 35302
    • Gabinet Lekarski Bartosz Korczowski
  • Sopot, Poland, 81756
    • Specialized Medical Practice. Dr med. Marek Horynski
  • Szczecin, Poland, 71270
    • Twoja Przychodnia-Szczecinskie Centrum Medyczne
• Russian Federation
  • Barnaul, Russian Federation, 656043
    • Multidisciplinary Medical Clinic "Anthurium"
  • Kemerovo, Russian Federation, 650066
    • GUZ Reg. Clinical Hospital, Kemerovo
  • Moscow, Russian Federation, 127015
    • Clinical Hospital No. 24, Moscow
  • Murmansk, Russian Federation, 183047
    • Murmansk Regional Clinical Hospital named after Bayandin
  • Nizhniy Novgorod, Russian Federation, 603126
    • Reg.Clin.Hosp.n.a.Semashko
  • Novosibirsk, Russian Federation, 630117
    • FSBSI "Scientific and Research Institute of Physiology and Basic Medicine"
  • Novosibirsk, Russian Federation, 630091
    • State Novosibirsk regional clinical hospital
  • Omsk, Russian Federation, 644013
    • BHI of Omsk region - Clinical Oncology Dispensary
  • Saint Petersburg, Russian Federation, 194291
    • SBIH City Clinical Hospital #31
  • Saint Petersburg, Russian Federation, 197110
    • LLC IClinic
  • Samara, Russian Federation, 443001
    • Private Educational Institution of Higher Education "Medical University "REAVIZ"
  • Samara, Russian Federation, 443041
    • NonState Healthcare Institution Central Clinical Hospital, Samara station JSC "Russian Railways"
  • St. Petersburg, Russian Federation, 194356
    • Baltic Med,LLC Clinic BaltMed Ozerki
  • St. Petersburg, Russian Federation, 196143
    • EKO-Bezopasnost, St. Petersburg
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11080
    • Clinical Center Zemun
  • Belgrade, Serbia, 11000
    • Clinical Medical Center Zvezdara, Belgrade
  • Belgrade, Serbia, 11080
    • Clinical Center Bezanijska kosa, Belgrade
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
• Turkey
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty
  • Gaziantep, Turkey, 27310
    • Gaziantep University Medical Faculty Sahinbey Educational Research Hospital
  • Istanbul, Turkey, 34890
    • Kartal Lutfi Kirdar Research and Training Hospital
  • Kocaeli, Turkey, 41380
    • Kocaeli University Research and Training Hospital
• Ukraine
  • Cherkasy, Ukraine, 18009
    • CI Cherkasy RH of Cherkasy Reg.Council
  • Kharkiv, Ukraine, 61037
    • CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2
  • Kiev, Ukraine, 02091
    • Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC
  • Kirovohrad, Ukraine, 25006
    • Private Enterprise Private Manufacturing Company "Acinus"
  • Kyiv, Ukraine, 01601
    • Medical Center Medical Clinic Kyiv
  • Kyiv, Ukraine, 04201
    • Clin Hosp.8 P.L.Shupyk NMA of PGE
  • Vinnytsia, Ukraine, 21018
    • M.I. Pyrogov VRCH, Vinnytsia
  • Vinnytsia, Ukraine, 21005
    • Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3
  • Zaporizhzhia, Ukraine, 69104
    • Clin.Hosp#1,Zaporizhzhia
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth and Christchurch Hospital
  • Walsall, United Kingdom, WS2 9PS
    • Walsall Manor Hospital
• United States
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Kissimmee, Florida, United States, 34741
      • Hope Clinical Research
    • Maitland, Florida, United States, 32751
      • Center for Advanced GI
    • Miami, Florida, United States, 33155
      • Advance Medical Research Center
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute, Inc
  • Georgia
    • East Point, Georgia, United States, 30344
      • Doctors Clinical Research
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Southwest Gastroenterology
  • Kansas
    • Kansas City, Kansas, United States, 66160-7702
      • University of Kansas Medical Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • MGG Group Co. Inc. / Chevy Chase Clinical Research,
    • Columbia, Maryland, United States, 21045
      • Gastro Center of Maryland
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, PA
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Gastroenterology Associates, PA
  • Texas
    • Houston, Texas, United States, 77079
      • Houston Endoscopy and Research Center
    • Katy, Texas, United States, 77450
      • Biopharma Informatic, Inc, dba Research Consultants
    • San Antonio, Texas, United States, 78229
      • Sagact, Pllc
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Healthcare
    • Victoria, Texas, United States, 77904
      • Victoria Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Males and females aged >=18 and =<80 years at Screening who have a diagnosis of moderate to severely active Crohn's Disease (CD), confirmed by endoscopy or radiologic evaluation, for more than 4 months with evidence of mucosal ulceration. Patients must have all of the following:

  • Crohn's Disease Activity Index (CDAI) score of >=220 and =<450
  • A diagnosis of Crohn's Disease (CD) confirmed by ileocolonoscopy during Screening
  • Presence of mucosal ulcers in at least one segment of the ileum or colon and a SES-CD score ≥7 (for patients with isolated ileal disease SES-CD score ≥4), as assessed by ileocolonoscopy and confirmed by central independent reviewer(s) before randomization

• Anti-tumor necrosis factor (TNF) patients or patients previously treated with infliximab who had initially responded and who meet one of the following criteria:

  • Responded and developed secondary resistance due confirmed anti-infliximab anti-drug antibody formation, which caused infliximab depletion
  • Responded and became intolerant
• Further inclusion criteria apply

Exclusion criteria:

• Patients with ulcerative colitis or indeterminate colitis
• Patients with symptomatic known obstructive strictures
• Surgical bowel resection performed within 6 months prior to Screening or planned resection at any time while enrolled in the trial
• Patients with an ostomy or ileoanal pouch
• Patients with short bowel syndrome
• Patients who have previously used infliximab and have never clinically responded
• Patients who have previously received treatment with adalimumab, or who have participated in an adalimumab or adalimumab biosimilar clinical trial
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 695501	Drug: BI 695501
Active Comparator: HUMIRA + BI 695501	Drug: BI 695501; Drug: HUMIRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With a Clinical Response (CDAI Decrease of ≥70 Compared With Baseline) at Week 4	The Crohn's Disease Activity Index (CDAI) is a validated instrument to measure disease severity in Crohn's Disease (CD). The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. The CDAI decrease at Week 4 was assessed as the decrease relative to baseline measurement, patients with a decrease ≥70 were responders. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to non-responder imputation (NRI) and last observation carried forward (LOCF).	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With a Clinical Response (CDAI Decrease of ≥70 Compared With Baseline) at Week 24	The CDAI is a validated instrument to measure disease severity in CD. The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. The CDAI decrease at Week 24 was assessed as the decrease relative to baseline measurement, patients with a decrease ≥70 were responders. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to NRI and LOCF.	Week 24
Percentage of Patients in Clinical Remission (CDAI <150) at Week 24	The CDAI is a validated instrument to measure disease severity in CD. The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. Patients with CDAI <150 at Week 24 were considered as clinical remission cases. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to NRI and LOCF.	at Week 24
Percentage of Patients With Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESIs)	Analysis of AEs focused on treatment-emergent AEs (TEAEs). For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46. TEAEs and SAEs (including investigator-assessed trial medication-related TEAEs) and AESIs are reported. The following were considered an AESI: hepatic injury, anaphylactic reactions, serious infection and hypersensitivity reactions.	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.
Percentage of Patients With Infections	The percentage of patients with TEAEs for infections are reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.
Percentage of Patients With Serious Infections	The percentage of patients with TEAEs for serious infections are reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.
Percentage of Patients Who Experienced Hypersensitivity Reactions	The percentage of patients with TEAEs for hypersensitivity reactions is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.
Percentage of Patients Who Experienced Drug Induced Liver Injury (DILI)	The percentage of patients with TEAEs for DILIs is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.
Percentage of Patients With Injection Site Reactions	The percentage of patients with TEAEs for injection site reactions is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Hanauer S, Liedert B, Balser S, Brockstedt E, Moschetti V, Schreiber S. Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn's disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):816-825. doi: 10.1016/S2468-1253(21)00252-1. Epub 2021 Aug 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2016
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): May 13, 2019

Study Registration Dates

• First Submitted: August 15, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: May 29, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: 1297.4; 2016-000612-14 (EudraCT Number)