Crohn's Disease
Conditions
Keywords
MEDI2070, inflammatory bowel disease, moderate to severe Crohn's disease
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.
Interventions
DRUGMEDI2070
1 iv infusion on Week 0 and Week 4
DRUGplacebo
1 iv infusion on Week 0 and Week 4
Sponsors
MedImmune Ltd
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With CDAI Response at Week 12 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Percentage of Participants With CDAI-70 Point Improvement at Week 8 | 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. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | 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. |
Countries
Canada, Czechia, France, Germany, Hungary, Italy, Poland, Spain, United States
Participant flow
Pre-assignment details
Out of 174 screened subjects, 53 were considered screen failures. A total of 121 subjects were randomized, of which 2 did not receive study drug. Those 2 subjects were not included in the mITT population; therefore, those subjects are not counted in the participant flow.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4. | 60 |
| Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4. | 59 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blinded Induction Period | Adverse Event | 0 | 1 | 0 | 0 |
| Double-Blinded Induction Period | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Double-Blinded Induction Period | Subject not in open label period | 3 | 1 | 0 | 0 |
| Double-Blinded Induction Period | Withdrawal by Subject | 5 | 3 | 0 | 0 |
| Open-Label Period | Adverse Event | 0 | 0 | 1 | 0 |
| Open-Label Period | Developed specific withdrawal criteria | 0 | 0 | 5 | 2 |
| Open-Label Period | Lost to Follow-up | 0 | 0 | 3 | 4 |
| Open-Label Period | Other | 0 | 0 | 1 | 3 |
| Open-Label Period | Withdrawal by Subject | 0 | 0 | 9 | 19 |
Baseline characteristics
| Characteristic | Placebo | Experimental: MEDI2070 700mg | Total |
|---|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 10.7 | 34.8 years STANDARD_DEVIATION 11.1 | 36.45 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 37 Participants | 37 Participants | 74 Participants |
| Sex: Female, Male Male | 23 Participants | 22 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 60 | 38 / 59 | 43 / 52 | 42 / 52 |
| serious Total, serious adverse events | 5 / 60 | 5 / 59 | 8 / 52 | 12 / 52 |
Outcome results
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.
Time frame: Week 8
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8 | 26.7 Percentage of Participants |
| Experimental: MEDI2070 700mg | Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8 | 49.2 Percentage of Participants |
p-value: =0.0190% CI: [8.3, 36.8]Regression, Logistic
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.
Time frame: Week 8
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in CDAI Total Score at Week 8 | -62.7 Scores on a scale | Standard Error 13.5 |
| Experimental: MEDI2070 700mg | Change From Baseline in CDAI Total Score at Week 8 | -99.0 Scores on a scale | Standard Error 15 |
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).
Time frame: Post-dose on Week 0 (Day 1); pre and post-dose on Week 4; pre-dose on Week 8
Population: Serum MEDI2070 concentration data was summarized descriptively by visit. Value of 0 represents the open-label portion of the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 0 Post-dose (60, 58) | NA mcg/ML | — |
| Placebo | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 4 Pre-dose (54, 53) | NA mcg/ML | — |
| Placebo | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 4 Post-dose (52, 51) | NA mcg/ML | — |
| Placebo | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 8 Pre-dose (55, 51) | NA mcg/ML | — |
| Experimental: MEDI2070 700mg | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 8 Pre-dose (55, 51) | 39.2 mcg/ML | Standard Deviation 18.4 |
| Experimental: MEDI2070 700mg | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 0 Post-dose (60, 58) | 186 mcg/ML | Standard Deviation 83.8 |
| Experimental: MEDI2070 700mg | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 4 Post-dose (52, 51) | 209 mcg/ML | Standard Deviation 68.9 |
| Experimental: MEDI2070 700mg | Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period | Week 4 Pre-dose (54, 53) | 37.4 mcg/ML | Standard Deviation 52.3 |
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).
Time frame: Pre-dose on Weeks 12, 24, and 112
Population: Serum MEDI2070 concentration data was summarized descriptively by visit. Value of 0 represents the double-blind portion of the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/MEDI2070 210mg | Maximum Mean Serum Concentration of MEDI2070 in Open-label Period | Week 12 Pre-dose (51, 52) | NA mcg/ML | — |
| Placebo/MEDI2070 210mg | Maximum Mean Serum Concentration of MEDI2070 in Open-label Period | Week 24 Pre-dose (48, 43) | 14.5 mcg/ML | Standard Deviation 7 |
| Placebo/MEDI2070 210mg | Maximum Mean Serum Concentration of MEDI2070 in Open-label Period | Week 112 Pre-dose (24, 20) | 18.3 mcg/ML | Standard Deviation 7.73 |
| MEDI2070 700mg/MEDI2070 210mg | Maximum Mean Serum Concentration of MEDI2070 in Open-label Period | Week 12 Pre-dose (51, 52) | 16.7 mcg/ML | Standard Deviation 11.8 |
| MEDI2070 700mg/MEDI2070 210mg | Maximum Mean Serum Concentration of MEDI2070 in Open-label Period | Week 24 Pre-dose (48, 43) | 15.1 mcg/ML | Standard Deviation 6.38 |
| MEDI2070 700mg/MEDI2070 210mg | Maximum Mean Serum Concentration of MEDI2070 in Open-label Period | Week 112 Pre-dose (24, 20) | 22.4 mcg/ML | Standard Deviation 7.97 |
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.
Time frame: Up to 28 week post last dose (approximately 140 weeks)
Population: Value of 0 represents the double-blind portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo/MEDI2070 210mg | Number of Participants With ADA Positive to MEDI2070 in Open-label Period | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With ADA Positive to MEDI2070 in Open-label Period | 1 Participants |
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.
Time frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Neutropenia | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Urine Abnormality | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Leukopenia | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Urine bilirubin increased | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Urine analysis Abnormal | 1 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Proteinuria | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Anaemia | 2 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Proteinuria | 1 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Anaemia | 1 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Leukopenia | 1 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Neutropenia | 1 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Urine analysis Abnormal | 0 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Urine Abnormality | 1 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period | Urine bilirubin increased | 1 Participants |
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.
Time frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Population: Value of 0 represents the double-blind portion of the trial
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Anaemia | 5 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Lymphocyte | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Lymphopenia | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Neutrophil count increased | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Platelet count increased | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Red cell distribution width increased | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | White blood cell count decreased | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Chromaturia | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Blood uric acid increased | 1 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Hypokalaemia | 1 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Hepatic enzyme increased | 0 Participants |
| Placebo/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Hyperlipidemia | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Hepatic enzyme increased | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Anaemia | 5 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | White blood cell count decreased | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Lymphocyte | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Hypokalaemia | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Lymphopenia | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Chromaturia | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Neutrophil count increased | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Hyperlipidemia | 0 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Platelet count increased | 1 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Blood uric acid increased | 0 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period | Red cell distribution width increased | 1 Participants |
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.
Time frame: Baseline (Week0/Day 1) up to 28 week post last dose (approximately 40 weeks)
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period | 0 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period | 1 Participants |
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.
Time frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Population: Value of 0 represents the double-blind portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo/MEDI2070 210mg | Number of Participants With TEAEs in Open-label Period | 44 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With TEAEs in Open-label Period | 43 Participants |
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.
Time frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Population: Value of 0 represents the double-blind portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo/MEDI2070 210mg | Number of Participants With TESAEs in Open-label Period | 8 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With TESAEs in Open-label Period | 12 Participants |
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.
Time frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period | 41 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period | 40 Participants |
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.
Time frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period | 5 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period | 5 Participants |
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.
Time frame: From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks)
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period | 0 Participants |
| Experimental: MEDI2070 700mg | Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period | 0 Participants |
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.
Time frame: From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks)
Population: Value of 0 represents the double-blind portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo/MEDI2070 210mg | Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period | 0 Participants |
| MEDI2070 700mg/MEDI2070 210mg | Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period | 0 Participants |
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.
Time frame: Week 8
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With CDAI-100 Point Improvement at Week 8 | 25.0 Percentage of Participants |
| Experimental: MEDI2070 700mg | Percentage of Participants With CDAI-100 Point Improvement at Week 8 | 45.8 Percentage of Participants |
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.
Time frame: Week 8
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With CDAI-70 Point Improvement at Week 8 | 46.7 Percentage of Participants |
| Experimental: MEDI2070 700mg | Percentage of Participants With CDAI-70 Point Improvement at Week 8 | 52.5 Percentage of Participants |
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.
Time frame: Week 8
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With CDAI Remission at Week 8 | 15 Percentage of Participants |
| Experimental: MEDI2070 700mg | Percentage of Participants With CDAI Remission at Week 8 | 27.1 Percentage of Participants |
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.
Time frame: Week 12
Population: Value of 0 represents the open-label portion of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With CDAI Response at Week 12 | 28.3 Percentage of Participants |
| Experimental: MEDI2070 700mg | Percentage of Participants With CDAI Response at Week 12 | 37.3 Percentage of Participants |