Trial Outcomes & Findings for Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease. (NCT NCT01714726)

Last Updated: 2021-05-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

121 participants

Primary outcome timeframe

Week 8

Results posted on

2021-05-26

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Double-Blinded Induction Period STARTED	60	59	0	0
Double-Blinded Induction Period COMPLETED	52	52	0	0
Double-Blinded Induction Period NOT COMPLETED	8	7	0	0
Open-Label Period STARTED	0	0	52	52
Open-Label Period COMPLETED	0	0	33	24
Open-Label Period NOT COMPLETED	0	0	19	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Double-Blinded Induction Period Subject not in open label period	3	1	0	0
Double-Blinded Induction Period Adverse Event	0	1	0	0
Double-Blinded Induction Period Withdrawal by Subject	5	3	0	0
Double-Blinded Induction Period Lost to Follow-up	0	2	0	0
Open-Label Period Other	0	0	1	3
Open-Label Period Adverse Event	0	0	1	0
Open-Label Period Withdrawal by Subject	0	0	9	19
Open-Label Period Developed specific withdrawal criteria	0	0	5	2
Open-Label Period Lost to Follow-up	0	0	3	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Total n=119 Participants Total of all reporting groups
Age, Continuous	38.1 years STANDARD_DEVIATION 10.7 • n=5 Participants	34.8 years STANDARD_DEVIATION 11.1 • n=7 Participants	36.45 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	37 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Value of 0 represents the open-label portion of the trial

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8	26.7 Percentage of Participants	49.2 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Week 8

Population: Value of 0 represents the open-label portion of the trial

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Percentage of Participants With CDAI-70 Point Improvement at Week 8	46.7 Percentage of Participants	52.5 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Week 12

Population: Value of 0 represents the open-label portion of the trial

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Percentage of Participants With CDAI Response at Week 12	28.3 Percentage of Participants	37.3 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Week 8

Population: Value of 0 represents the open-label portion of the trial

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Percentage of Participants With CDAI Remission at Week 8	15 Percentage of Participants	27.1 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Week 8

Population: Value of 0 represents the open-label portion of the trial

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Percentage of Participants With CDAI-100 Point Improvement at Week 8	25.0 Percentage of Participants	45.8 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Week 8

Population: Value of 0 represents the open-label portion of the trial

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Change From Baseline in CDAI Total Score at Week 8	-62.7 Scores on a scale Standard Error 13.5	-99.0 Scores on a scale Standard Error 15.0	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period	41 Participants	40 Participants	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period	5 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 Participants Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 Participants Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With TEAEs in Open-label Period	—	—	44 Participants	43 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 Participants Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 Participants Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With TESAEs in Open-label Period	—	—	8 Participants	12 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Anaemia	2 Participants	1 Participants	—	—
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Leukopenia	0 Participants	1 Participants	—	—
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Neutropenia	0 Participants	1 Participants	—	—
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Urine analysis Abnormal	1 Participants	0 Participants	—	—
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Urine Abnormality	0 Participants	1 Participants	—	—
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Urine bilirubin increased	0 Participants	1 Participants	—	—
Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period Proteinuria	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 Participants Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 Participants Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Anaemia	—	—	5 Participants	5 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Lymphocyte	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Lymphopenia	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Neutrophil count increased	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Platelet count increased	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Red cell distribution width increased	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period White blood cell count decreased	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Chromaturia	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Blood uric acid increased	—	—	1 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Hypokalaemia	—	—	1 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Hepatic enzyme increased	—	—	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period Hyperlipidemia	—	—	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 Participants Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 Participants Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period	—	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period Week 0 Post-dose (60, 58)	NA mcg/ML Standard Deviation NA Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frame	186 mcg/ML Standard Deviation 83.8	—	—
Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period Week 4 Pre-dose (54, 53)	NA mcg/ML Standard Deviation NA Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frame	37.4 mcg/ML Standard Deviation 52.3	—	—
Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period Week 4 Post-dose (52, 51)	NA mcg/ML Standard Deviation NA Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frame	209 mcg/ML Standard Deviation 68.9	—	—
Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period Week 8 Pre-dose (55, 51)	NA mcg/ML Standard Deviation NA Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frame	39.2 mcg/ML Standard Deviation 18.4	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 Participants Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 Participants Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Maximum Mean Serum Concentration of MEDI2070 in Open-label Period Week 12 Pre-dose (51, 52)	—	—	NA mcg/ML Standard Deviation NA Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frames	16.7 mcg/ML Standard Deviation 11.8
Maximum Mean Serum Concentration of MEDI2070 in Open-label Period Week 24 Pre-dose (48, 43)	—	—	14.5 mcg/ML Standard Deviation 7.0	15.1 mcg/ML Standard Deviation 6.38
Maximum Mean Serum Concentration of MEDI2070 in Open-label Period Week 112 Pre-dose (24, 20)	—	—	18.3 mcg/ML Standard Deviation 7.73	22.4 mcg/ML Standard Deviation 7.97

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 Participants Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 28 week post last dose (approximately 140 weeks)

Population: Value of 0 represents the double-blind portion of the trial

Outcome measures

Outcome measures
Measure	Placebo Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 Participants Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 Participants Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Number of Participants With ADA Positive to MEDI2070 in Open-label Period	—	—	1 Participants	1 Participants

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Experimental: MEDI2070 700mg

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo/MEDI2070 210mg

Serious events: 8 serious events

Other events: 43 other events

Deaths: 0 deaths

MEDI2070 700mg/MEDI2070 210mg

Serious events: 12 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Study Information Center

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo. (Note that this agreement language may appear in the study protocol)
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=60 participants at risk Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.	Experimental: MEDI2070 700mg n=59 participants at risk Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.	Placebo/MEDI2070 210mg n=52 participants at risk Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.	MEDI2070 700mg/MEDI2070 210mg n=52 participants at risk Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.
Vascular disorders Shock	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Injury, poisoning and procedural complications Intestinal anastomosis complication	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Injury, poisoning and procedural complications Accidental exposure to product	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Blood and lymphatic system disorders Anemia	1.7% 1/60 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Blood and lymphatic system disorders Lymphopenia	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Nervous system disorders Seizure	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
General disorders Pyrexia	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.7% 1/59 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
General disorders Adverse drug reaction	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Gastrointestinal disorders Crohn's disease	3.3% 2/60 • Number of events 2 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	3.4% 2/59 • Number of events 2 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	11.5% 6/52 • Number of events 6 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Gastrointestinal disorders Diarrhoea	1.7% 1/60 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Gastrointestinal disorders Gastrointestinal haemorrhage	1.7% 1/60 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Gastrointestinal disorders Large intestine perforation	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.7% 1/59 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Gastrointestinal disorders Abdominal pain	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Gastrointestinal disorders Anal fistula	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Renal and urinary disorders Nephrolithiasis	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Metabolism and nutrition disorders Dehydration	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Abdominal abscess	1.7% 1/60 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Cellulitis	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.7% 1/59 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Pelvic abscess	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Pyelonephritis	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Anal abscess	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	23.1% 12/52 • Number of events 12 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Subcutaneous abscess	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)
Infections and infestations Peritonitis	0.00% 0/60 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/59 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	1.9% 1/52 • Number of events 1 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)	0.00% 0/52 • From study drug administration (Day 1) to 36 weeks post last dose (approximately 148 weeks)