Clinical trial NCT01714726: Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease.
Official title: A Phase 2a Study to Evaluate the Efficacy and Safety of MEDI2070 in Subjects With Moderate to Severe Crohn's Disease Who Have Failed or Are Intolerant to Anti-tumor Necrosis Factor-alpha Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: MEDI2070
inflammatory bowel disease
moderate to severe Crohn's disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: MedImmune Ltd
First posted: 2012-10-26
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to evaluate the clinical efficacy and safety of MEDI2070 as compared to placebo. Investigational product will be administered as intravenous infusion in double-blind period, and as a subcutaneous injection in open-label period

Detailed description: This is a two-part Phase 2a study compromising a 12-week, double-blind, placebo-controlled, treatment period followed by a 100-week, open label, treatment period to evaluate short-term efficacy, and the short- and long-term safety of MEDI2070 in subjects with moderate to severe, active CD who have failed or are intolerant to anti-TNFα therapy as determined by the investigator. Approximately 120 subjects will be randomized in a 1:1 ratio to initially receive a fixed IV dose of MEDI2070 or placebo on Week 0(Day1) and Week 4 (Day 29) during the 12-week, double-blind, placebo-controlled, treatment period. At the completion of the double-blind, placebo-controlled, treatment period (Week 12), subjects will have the option to enter a 100-week, open-label, treatment period where they will receive open-label MEDI2070 (SC) Q4W (Week 12 through Week 112). Subjects will be followed for safety at 3 visits over 28 weeks after their last dose of IP. Subjects will also be contacted by phone 36 weeks after their last dose of IP for safety.

Eligibility criteria: Inclusion Criteria:

* Diagnosed ileal, ileo-colonic, or colonic CD at least 6 months prior to screening.
* Men or women age 18 - 65 years at the time of screening.
* Moderate-sever active Crohn's Disease (CD), defined by a Crohn's Disease Activity Index (CDAI) score higher or equal 220 and lower or equal 450 at Day 1.
* No known history of active tuberculosis (TB).
* Received at least one anti-TNFα agent for the treatment of CD and did not initially respond.

Exclusion Criteria:

* Pregnant or breastfeeding women.
* Presence of ileostomy and/or colostomy.
* Short bowel syndrome.
* Bowel perforation or obstruction.
* History of cancer.

Primary outcomes:
measure: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants With CDAI-70 Point Improvement at Week 8
timeFrame: Week 8
measure: Percentage of Participants With CDAI Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants With CDAI Remission at Week 8
timeFrame: Week 8
measure: Percentage of Participants With CDAI-100 Point Improvement at Week 8
timeFrame: Week 8
measure: Change From Baseline in CDAI Total Score at Week 8
timeFrame: Week 8
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period
timeFrame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
measure: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period
timeFrame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
measure: Number of Participants With TEAEs in Open-label Period
timeFrame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
measure: Number of Participants With TESAEs in Open-label Period
timeFrame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
measure: Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period
timeFrame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period
timeFrame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
measure: Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period
timeFrame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
measure: Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period
timeFrame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
measure: Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period
timeFrame: Post-dose on Week 0 (Day 1); pre and post-dose on Week 4; pre-dose on Week 8
measure: Maximum Mean Serum Concentration of MEDI2070 in Open-label Period
timeFrame: Pre-dose on Weeks 12, 24, and 112
measure: Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period
timeFrame: Baseline (Week0/Day 1) up to 28 week post last dose (approximately 40 weeks)
measure: Number of Participants With ADA Positive to MEDI2070 in Open-label Period
timeFrame: Up to 28 week post last dose (approximately 140 weeks)
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
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state: California
city: Lakewood
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state: Colorado
city: Jacksonville
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state: Florida
city: Miami
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state: Florida
city: Winter Park
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state: Florida
city: Macon
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state: Georgia
city: Chicago
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state: Illinois
city: Baton Rouge
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state: Louisiana
city: Hammond
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state: Louisiana
city: Baltimore
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state: Maryland
city: Chevy Chase
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city: Ann Arbor
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state: Michigan
city: Troy
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state: Michigan
city: Belton
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state: Missouri
city: New York
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state: New York
city: New York
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state: New York
city: Asheville
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state: North Carolina
city: Charlotte
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city: Cincinnati
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state: Ohio
city: Lima
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state: Tennessee
city: San Antonio
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state: Texas
city: Seattle
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state: Washington
city: Edmonton
country: Canada
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state: Alberta
city: Vancouver
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state: British Columbia
city: St. John's
country: Canada
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state: Newfoundland and Labrador
city: Guelph
country: Canada
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state: Ontario
city: Kingston
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: Ottawa
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Vaughan
country: Canada
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state: Ontario
city: Montreal
country: Canada
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state: Quebec
city: Ceske Budejovice
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Litomerice
country: Czechia
facility: Research Site
city: Ostrava-Poruba
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Praha 7
country: Czechia
facility: Research Site
city: Amiens Cedex 1
country: France
facility: Research Site
city: Clichy
country: France
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city: Pessac
country: France
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city: Rouen
country: France
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city: Toulouse Cedex 9
country: France
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city: Hamburg
country: Germany
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city: Hamburg
country: Germany
facility: Research Site
city: Munchen
country: Germany
facility: Research Site
city: Potsdam
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Kaposvar
country: Hungary
facility: Research Site
city: Szombathely
country: Hungary
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Opole
country: Poland
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city: Rzeszow
country: Poland
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city: Sopot
country: Poland
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city: Sosnowiec
country: Poland
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city: Warszawa
country: Poland
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city: Wroclaw
country: Poland
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Sabadell(Barcelona)
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
Study officials:
References:
citation: Sands BE, Chen J, Feagan BG, Penney M, Rees WA, Danese S, Higgins PDR, Newbold P, Faggioni R, Patra K, Li J, Klekotka P, Morehouse C, Pulkstenis E, Drappa J, van der Merwe R, Gasser RA Jr. Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study. Gastroenterology. 2017 Jul;153(1):77-86.e6. doi: 10.1053/j.gastro.2017.03.049. Epub 2017 Apr 5.