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

Crohn Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02871635
• Other study ID #: 1297.4
• Secondary ID: 2016-000612-14
• Status: Completed
• Phase: Phase 3
• Start date: September 28, 2016
• Est. completion date: May 13, 2019

Study information

• Verified date: May 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: May 13, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• BI 695501

• HUMIRA

Locations

Country	Name	City	State
Belarus	Gomel Regional Clinical	Gomel
Belarus	City Clinical Hospital # 10	Minsk
Belarus	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk
Bosnia and Herzegovina	University Clinical Centre Sarajevo	Sarajevo
Croatia	Clinical Hospital Osijek	Osijek
Croatia	Polyclinic Bonifarm	Zagreb
Czechia	Vojenska nemocnice Brno	Brno
Czechia	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove
Czechia	CTCenter Mave, s.r.o., Cllinical Trials Center, Olomouc	Olomouc
Czechia	Gregar s.r.o.	Olomouc
Czechia	PreventaMed, s.r.o.	Olomouc
Czechia	University Hospital Ostrava	Ostrava-Poruba
Czechia	Vitkovice Hospital	Ostrava-Vitkovice
Czechia	Medicon, a.s.	Prague
Czechia	Axon Clinical, s.r.o.	Praha
Czechia	University Hospital Na Bulovce	Praha 8
Czechia	General Hospital Pribram	Pribram
Czechia	Masaryk Hospital, Internal Department	Usti nad Labem
Germany	Crohn Colitis Centrum Rhein Main	Frankfurt
Greece	General Hospital of Athens Evangelismos	Athens
Greece	University General Hospital of Heraklion	Heraklion, Crete
Greece	General Hospital of Rhodes	Rhodes
Israel	Haemek Medical Center	Afula
Israel	Wolfson Medical Center	Holon
Israel	Hadassah Medical Center, Ein-Karem	Jerusalem
Israel	Meir Medical Center	Kfar-Saba
Israel	The Chaim Sheba Medical Center Tel Hashomer	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Poland	KLIMED Marek Klimkiewicz	Bialystok
Poland	NZOZ Centrum Medyczne KERmed	Bydgoszcz
Poland	Medical Center Pleiades	Cracow
Poland	Polimedica Centrum Badan	Kielce
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla	Knurow
Poland	SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia	Lodz
Poland	Clinic Medical Center; Nowa Sol	Nowa Sol
Poland	Ai Medical Center, private practice, Poznan	Poznan
Poland	Gabinet Lekarski Bartosz Korczowski	Rzeszow
Poland	Specialized Medical Practice. Dr med. Marek Horynski	Sopot
Poland	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin
Russian Federation	Multidisciplinary Medical Clinic "Anthurium"	Barnaul
Russian Federation	GUZ Reg. Clinical Hospital, Kemerovo	Kemerovo
Russian Federation	Clinical Hospital No. 24, Moscow	Moscow
Russian Federation	Murmansk Regional Clinical Hospital named after Bayandin	Murmansk
Russian Federation	Reg.Clin.Hosp.n.a.Semashko	Nizhniy Novgorod
Russian Federation	FSBSI "Scientific and Research Institute of Physiology and Basic Medicine"	Novosibirsk
Russian Federation	State Novosibirsk Regional Clinical Hospital	Novosibirsk
Russian Federation	BHI of Omsk region - Clinical Oncology Dispensary	Omsk
Russian Federation	LLC IClinic	Saint Petersburg
Russian Federation	SBIH City Clinical Hospital #31	Saint Petersburg
Russian Federation	NonState Healthcare Institution Central Clinical Hospital, Samara station JSC "Russian Railways"	Samara
Russian Federation	Private Educational Institution of Higher Education "Medical University "REAVIZ"	Samara
Russian Federation	Baltic Med,LLC Clinic BaltMed Ozerki	St. Petersburg
Russian Federation	EKO-Bezopasnost, St. Petersburg	St. Petersburg
Serbia	Clinical Center Bezanijska kosa, Belgrade	Belgrade
Serbia	Clinical Center Zemun	Belgrade
Serbia	Clinical Medical Center Zvezdara, Belgrade	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Gaziantep University Medical Faculty Sahinbey Educational Research Hospital	Gaziantep
Turkey	Kartal Lutfi Kirdar Research and Training Hospital	Istanbul
Turkey	Kocaeli University Research and Training Hospital	Kocaeli
Ukraine	CI Cherkasy RH of Cherkasy Reg.Council	Cherkasy
Ukraine	CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2	Kharkiv
Ukraine	Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC	Kiev
Ukraine	Private Enterprise Private Manufacturing Company "Acinus"	Kirovohrad
Ukraine	Clin Hosp.8 P.L.Shupyk NMA of PGE	Kyiv
Ukraine	Medical Center Medical Clinic Kyiv	Kyiv
Ukraine	M.I. Pyrogov VRCH, Vinnytsia	Vinnytsia
Ukraine	Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3	Vinnytsia
Ukraine	Clin.Hosp#1,Zaporizhzhia	Zaporizhzhia
United Kingdom	Royal Bournemouth and Christchurch Hospital	Bournemouth
United Kingdom	Walsall Manor Hospital	Walsall
United States	Asheville Gastroenterology Associates, PA	Asheville	North Carolina
United States	MGG Group Co. Inc. / Chevy Chase Clinical Research,	Chevy Chase	Maryland
United States	Gastro Center of Maryland	Columbia	Maryland
United States	Doctors Clinical Research	East Point	Georgia
United States	Gastroenterology Associates, PA	Greenville	South Carolina
United States	Healthcare Research Network	Hazelwood	Missouri
United States	Houston Endoscopy and Research Center	Houston	Texas
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Biopharma Informatic, Inc, dba Research Consultants	Katy	Texas
United States	Hope Clinical Research	Kissimmee	Florida
United States	Center for Advanced GI	Maitland	Florida
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	Advance Medical Research Center	Miami	Florida
United States	Advanced Research Institute, Inc	New Port Richey	Florida
United States	Southwest Gastroenterology	Oak Lawn	Illinois
United States	Sagact, Pllc	San Antonio	Texas
United States	Baylor Scott and White Healthcare	Temple	Texas
United States	Victoria Gastroenterology	Victoria	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belarus,  Bosnia and Herzegovina,  Croatia,  Czechia,  Germany,  Greece,  Israel,  Poland,  Russian Federation,  Serbia,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.