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

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01714726
• Other study ID #: D5170C00001
• Secondary ID: EudraCT number:
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2013
• Est. completion date: December 14, 2016

Study information

• Verified date: May 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: December 14, 2016
• Est. primary completion date: May 20, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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-TNFa 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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• MEDI2070
1 iv infusion on Week 0 and Week 4
• placebo
1 iv infusion on Week 0 and Week 4

Locations

Country	Name	City	State
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Guelph	Ontario
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Vaughan	Ontario
Czechia	Research Site	Ceske Budejovice
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Litomerice
Czechia	Research Site	Ostrava-Poruba
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 7
France	Research Site	Amiens Cedex 1
France	Research Site	Clichy
France	Research Site	Pessac
France	Research Site	Rouen
France	Research Site	Toulouse Cedex 9
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Munchen
Germany	Research Site	Potsdam
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Kaposvar
Hungary	Research Site	Szombathely
Italy	Research Site	Bologna
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Poland	Research Site	Bydgoszcz
Poland	Research Site	Bydgoszcz
Poland	Research Site	Opole
Poland	Research Site	Rzeszow
Poland	Research Site	Sopot
Poland	Research Site	Sosnowiec
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Sabadell(Barcelona)
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Asheville	North Carolina
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Belton	Missouri
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chevy Chase	Maryland
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Encinitas	California
United States	Research Site	Germantown	Tennessee
United States	Research Site	Hammond	Louisiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Lakewood	Colorado
United States	Research Site	Lima	Ohio
United States	Research Site	Los Angeles	California
United States	Research Site	Macon	Georgia
United States	Research Site	Miami	Florida
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Seattle	Washington
United States	Research Site	Torrance	California
United States	Research Site	Troy	Michigan
United States	Research Site	Winter Park	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	MedImmune Ltd

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Poland,  Spain, 

References & Publications (1)

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. — View Citation

Outcome

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