Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease.

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

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

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: MEDI2070; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Research Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Research Site
  • Ontario
    • Guelph, Ontario, Canada, N1H 3R3
      • Research Site
    • Kingston, Ontario, Canada, K7L 5G2
      • Research Site
    • London, Ontario, Canada, N6A 5A5
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
    • Toronto, Ontario, Canada, M5G 1X5
      • Research Site
    • Toronto, Ontario, Canada, M6H 3M1
      • Research Site
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Research Site
• Czechia
  • Ceske Budejovice, Czechia, 370 01
    • Research Site
  • Hradec Kralove, Czechia, 500 12
    • Research Site
  • Litomerice, Czechia, 412 01
    • Research Site
  • Ostrava-Poruba, Czechia, 708 53
    • Research Site
  • Praha 10, Czechia, 100 34
    • Research Site
  • Praha 7, Czechia, 170 04
    • Research Site
• France
  • Amiens Cedex 1, France, 88054
    • Research Site
  • Clichy, France, 92210
    • Research Site
  • Pessac, France, 33604
    • Research Site
  • Rouen, France, F-76031 CE
    • Research Site
  • Toulouse Cedex 9, France, 31059
    • Research Site
• Germany
  • Hamburg, Germany, 20246
    • Research Site
  • Hamburg, Germany, 20249
    • Research Site
  • Munchen, Germany, 80331
    • Research Site
  • Potsdam, Germany, 14482
    • Research Site
• Hungary
  • Budapest, Hungary, 1125
    • Research Site
  • Budapest, Hungary, 1062
    • Research Site
  • Budapest, Hungary, 1081
    • Research Site
  • Kaposvar, Hungary, 7400
    • Research Site
  • Szombathely, Hungary, 9700
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Firenze, Italy, 50141
    • Research Site
  • Milano, Italy, 20100
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Roma, Italy, 133
    • Research Site
  • Roma, Italy, 196
    • Research Site
  • Rozzano, Italy, 20089
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-168
    • Research Site
  • Bydgoszcz, Poland, 85-681
    • Research Site
  • Opole, Poland, 45-061
    • Research Site
  • Rzeszow, Poland, 35-301
    • Research Site
  • Sopot, Poland, 81-756
    • Research Site
  • Sosnowiec, Poland
    • Research Site
  • Warszawa, Poland, 02-507
    • Research Site
  • Wroclaw, Poland, 53-333
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Barcelona, Spain, 8025
    • Research Site
  • Barcelona, Spain, 8916
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 8907
    • Research Site
  • Sabadell(Barcelona), Spain, 8208
    • Research Site
  • Sevilla, Spain, 41014
    • Research Site
  • Sevilla, Spain, 41071
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• United States
  • California
    • Encinitas, California, United States, 92024
      • Research Site
    • Los Angeles, California, United States, 45242
      • Research Site
    • San Diego, California, United States, 92114
      • Research Site
    • Torrance, California, United States, 90505
      • Research Site
  • Colorado
    • Lakewood, Colorado, United States, 80215
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Miami, Florida, United States, 33136
      • Research Site
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Georgia
    • Macon, Georgia, United States, 31201
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Research Site
    • Hammond, Louisiana, United States, 70403
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Research Site
    • Chevy Chase, Maryland, United States, 20815
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • Troy, Michigan, United States, 48098
      • Research Site
  • Missouri
    • Belton, Missouri, United States, 64012
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Research Site
    • Charlotte, North Carolina, United States, 28207
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Lima, Ohio, United States, 45806
      • Research Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; MEDI2070 iv infusion	Drug: MEDI2070; 1 iv infusion on Week 0 and Week 4
Placebo Comparator: 2; placebo iv infusion	Drug: placebo; 1 iv infusion on Week 0 and Week 4
Experimental: open-label; MEDI2070 sc injection; open-label arm is available for all subjects upon completion of first placebo-controlled treatment period	Drug: MEDI2070; 1 iv infusion on Week 0 and Week 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8	A CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days includes subject reported symptoms, physician-assessed signs, and laboratory markers. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity. The CDAI response at Week 8 is defined as either CDAI score of less than (<)150 or CDAI reduction from baseline of at least 100 points, where baseline was last non-missing observation prior to first administration of the study drug. Modified Intent-to-treat (mITT)population was analysed for this end point, which included all subjects who were randomized and received at least 1 dose of study drug in double-blind period.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With CDAI-70 Point Improvement at Week 8	The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. CDAI 70-point improvement is defined as a reduction from baseline in CDAI score of at least 70 points/scores, where baseline was the latest nonmissing observation prior to first administration of the study drug. Subjects in the mITT population were analysed for this end point.	Week 8
Percentage of Participants With CDAI Response at Week 12	The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. CDAI response is defined by either a CDAI score of < 150 or a CDAI reduction from baseline of at least 100 points, where baseline was the latest non-missing observation prior to first administration of the study drug. Subjects in the mITT population were analysed for this end point.	Week 12
Percentage of Participants With CDAI Remission at Week 8	The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. The CDAI score of < 150 represent CDAI remission. Subjects in the mITT population were analysed for this end point.	Week 8
Percentage of Participants With CDAI-100 Point Improvement at Week 8	The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. CDAI 100-point improvement is defined as a reduction from baseline in CDAI score of at least 100 points/scores, where baseline was the latest nonmissing observation prior to first administration of the study drug. Subjects in the mITT population were analysed for this end point.	Week 8
Change From Baseline in CDAI Total Score at Week 8	The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. Subjects in the mITT population were analysed for this end point.	Week 8
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period	An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, lifethreatening, a congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (approximately 48 weeks). The safety population was analysed for this end point, which included all subjects who received any amount of study drug.	From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period	An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, lifethreatening, a congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (approximately 48 weeks). The safety population was analysed for this end point, which included all subjects who received any amount of study drug.	From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Number of Participants With TEAEs in Open-label Period	An AE is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A SAE is any AE that resulted in death,inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, lifethreatening, a congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (approximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.	From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Number of Participants With TESAEs in Open-label Period	An AE is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A SAE is any AE that resulted in death,inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, lifethreatening, a congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (approximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.	From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period	The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (up to approximately 48 weeks). Subjects in the safety population were analysed for this end point.	From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period	The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1)to 36 weeks post treatment (up toapproximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.	From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period	The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1)to 36 weeks post treatment(approximately 48 weeks). Subjects in the safety population were analysed for this end point.	From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period	The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment(approximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.	From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period	Pharmacokinetic (PK) population included all subjects who received at least one dose of MEDI2070(either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point. Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frames and is reported by an arbitrary value (NA).	Post-dose on Week 0 (Day 1); pre and post-dose on Week 4; pre-dose on Week 8
Maximum Mean Serum Concentration of MEDI2070 in Open-label Period	The PK population included all subjects who received at least one dose of MEDI2070 (either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point. Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for pre-dose Week 12 time frame and is reported by an arbitrary value (NA).	Pre-dose on Weeks 12, 24, and 112
Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period	The PK population included all subjects who received at least one dose of MEDI2070 (either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point.	Baseline (Week0/Day 1) up to 28 week post last dose (approximately 40 weeks)
Number of Participants With ADA Positive to MEDI2070 in Open-label Period	The PK population included all subjects who received at least one dose of MEDI2070 (either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point.	Up to 28 week post last dose (approximately 140 weeks)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: MedImmune Ltd

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2013
• Primary Completion (Actual): May 20, 2014
• Study Completion (Actual): December 14, 2016

Study Registration Dates

• First Submitted: October 24, 2012
• First Submitted That Met QC Criteria: October 24, 2012
• First Posted (Estimate): October 26, 2012

Study Record Updates

• Last Update Posted (Actual): May 26, 2021
• Last Update Submitted That Met QC Criteria: May 7, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: inflammatory bowel disease; MEDI2070; moderate to severe Crohn's disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: D5170C00001; EudraCT number: 2012-004098-26; 2012-004098-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No