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Trial record 1 of 2 for:    medi2070 | Crohn Disease | Italy
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Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease.

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ClinicalTrials.gov Identifier: NCT01714726
Recruitment Status : Completed
First Posted : October 26, 2012
Results First Posted : March 6, 2019
Last Update Posted : May 26, 2021
Sponsor:
Collaborator:
MedImmune Ltd
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 24, 2012
First Posted Date  ICMJE October 26, 2012
Results First Submitted Date  ICMJE September 21, 2018
Results First Posted Date  ICMJE March 6, 2019
Last Update Posted Date May 26, 2021
Actual Study Start Date  ICMJE February 1, 2013
Actual Primary Completion Date May 20, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2019)
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2012)
The primary endpoint of the study is Crohn's Disease Activity Index (CDAI) response at Week 8, defined by either a CDAI score of < 150 or a CDAI reduction from baseline of at least 100 points [ Time Frame: Week 8 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2021)
  • Percentage of Participants With CDAI-70 Point Improvement at Week 8 [ Time Frame: 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.
  • Percentage of Participants With CDAI Response at Week 12 [ Time Frame: 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.
  • Percentage of Participants With CDAI Remission at Week 8 [ Time Frame: 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.
  • Percentage of Participants With CDAI-100 Point Improvement at Week 8 [ Time Frame: 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.
  • Change From Baseline in CDAI Total Score at Week 8 [ Time Frame: 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.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period [ Time Frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks) ]
    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.
  • Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period [ Time Frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks) ]
    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.
  • Number of Participants With TEAEs in Open-label Period [ Time Frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks) ]
    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.
  • Number of Participants With TESAEs in Open-label Period [ Time Frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks) ]
    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.
  • Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period [ Time Frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks) ]
    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.
  • Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period [ Time Frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks) ]
    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.
  • Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period [ Time Frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks) ]
    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.
  • Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period [ Time Frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks) ]
    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.
  • Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period [ Time Frame: Post-dose on Week 0 (Day 1); pre and post-dose on Week 4; pre-dose on Week 8 ]
    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).
  • Maximum Mean Serum Concentration of MEDI2070 in Open-label Period [ Time Frame: Pre-dose on Weeks 12, 24, and 112 ]
    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).
  • Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period [ Time Frame: Baseline (Week0/Day 1) up to 28 week post last dose (approximately 40 weeks) ]
    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.
  • Number of Participants With ADA Positive to MEDI2070 in Open-label Period [ Time Frame: Up to 28 week post last dose (approximately 140 weeks) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2012)
  • Crohn's Disease Activity Index (CDAI) remission at Week 8, as defined by a CDAI score of < 150 [ Time Frame: Week 8 ]
  • A reduction of at least 100 points from baseline in Crohn's Disease Activity Index (CDAI) at Week 8 [ Time Frame: Week 8 ]
  • A reduction of at least 70 points from baseline in Crohn's Disease Activity Index (CDAI) at Week 8 [ Time Frame: Week 8 ]
  • Crohn's Disease Activity Index (CDAI) response (either remission defined by CDAI < 150 or a CDAI reduction from baseline of at least 100 points from baseline) at Week 12 [ Time Frame: Week 12 ]
  • Change from baseline Crohn's Disease Activity Index (CDAI) at Week 8 [ Time Frame: Week 8 ]
  • Pharmacokinetic (PK) evaluation of Multiple Doses of MEDI2070 [ Time Frame: Week 0(Visit 3), Week 4 (Visit 5), Week 8 (Visit 6) predose; Week 0(Visit 3), Week 4 (Visit 5) postdose ]
  • Immunogenicity (IM) evaluation of Multiple Doses of MEDI2070 [ Time Frame: Week 0(Visit 3), Week 8 (Visit 6) postdose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease.
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: MEDI2070
    1 iv infusion on Week 0 and Week 4
  • Drug: placebo
    1 iv infusion on Week 0 and Week 4
Study Arms  ICMJE
  • Experimental: 1
    MEDI2070 iv infusion
    Intervention: Drug: MEDI2070
  • Placebo Comparator: 2
    placebo iv infusion
    Intervention: Drug: placebo
  • Experimental: open-label
    MEDI2070 sc injection; open-label arm is available for all subjects upon completion of first placebo-controlled treatment period
    Intervention: Drug: MEDI2070
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2018)
121
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2012)
120
Actual Study Completion Date  ICMJE December 14, 2016
Actual Primary Completion Date May 20, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Canada,   Czechia,   France,   Germany,   Hungary,   Poland,   Spain,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01714726
Other Study ID Numbers  ICMJE D5170C00001
EudraCT number: 2012-004098-26
2012-004098-26 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE MedImmune Ltd
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP