Colitis, Ulcerative
Conditions
Keywords
Active Ulcerative Colitis, Phase 2A, Double-blind, Randomized, PK/PD Biomarker Study
Brief summary
This study represents the first investigation of anrukinzumab in patients with active ulcerative colitis (UC) and will evaluate proof of mechanism by changes in the mechanism based biomarker (YKL 40) and pharmacodynamic biomarkers (fecal calprotectin, lactoferrin and hs-CRP). It will provide further assessment of the safety, tolerability, and pharmacokinetics (PK) by administration of multiple intravenous (IV) doses of anrukinzumab.
Interventions
BIOLOGICALAnrukinzumab
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
OTHERplacebo
200 mg liquid sterile vial, administered at matching dose level 200 mg, 400 mg or 600 mg intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female, Age \>=18 and \<=65 years * Active ulcerative colitis (UC) beyond the rectum based upon Mayo Score * women of childbearing potential with highly effective method of contraception
Exclusion criteria
* Indeterminate disease status, Crohn's disease, ischemic colitis, positive HIV, positive or history of tuberculosis infection, active enteric infections, transplant organ recipient, concomitant steroids, immunosuppressives or anti-TNFs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fold Change From Baseline in Fecal Calprotectin at Week 14 | Baseline, Week 14 | The fold change from baseline in fecal calprotectin at Week 14, is the ratio of the measurement of fecal calprotectin at Week 14 to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at Week 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Clearance (CL) for Anrukinzumab | Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Total Interleukin-13 (IL-13) Level | Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32 | — |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 32 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 32 that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study drug, which occurred during the trial. |
| Number of Participants Who Discontinued From the Study Due to Adverse Events | Baseline up to Week 32 | — |
| Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32 | Neutralizing antibody was not analyzed as no participant had positive ADA samples. |
| Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Baseline, Week 14 | Mayo score is used to measure the disease activity of ulcerative colitis. Endoscopy or flexible sigmoidoscopy is a sub score of Mayo score. The score for endoscopic subscore ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for endoscopy or flexible sigmoidoscopy at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score. |
| Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Pre-dose to end of the dosing interval after Day 1, Week 12 | Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12). |
| Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Pre-dose to end of the dosing interval after Day 1, Week 12 | Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12). |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab | Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2 | Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported. |
| Plasma Decay Half-Life (t1/2) for Anrukinzumab | Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Volume of Distribution (Vz) for Anrukinzumab | Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Baseline, Week 2, 4, 8, 12 | The fold change from baseline in fecal calprotectin at post-baseline visit, is the ratio of the measurement of fecal calprotectin at post-baseline visit to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at post-baseline visit. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Mayo Score at Week 14 | Baseline, Week 14 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy \[endoscopy\] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity. |
| Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Baseline, Week 14 | Stool frequency is a sub score of Mayo score used to measure the disease activity of ulcerative colitis. The score for stool frequency ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for stool frequency at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score. |
| Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Baseline, Week 14 | Mayo score is used to measure the disease activity of ulcerative colitis. Rectal bleeding is a sub score of Mayo score. The score for rectal bleeding ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for rectal bleeding at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score. |
| Clinical Response Rate at Week 14 | Week 14 | Clinical response rate is defined as percentage of participants with at least 3 point decrease from baseline in total Mayo score with at least 30% change along with 1 point decrease from baseline or absolute score of 0 or 1 in rectal bleeding. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy \[endoscopy\] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity. |
| Clinical Remission Rate at Week 14 | Week 14 | Clinical remission rate is defined as percentage of participants with a total Mayo score less than or equal to 2, with no individual subscore greater than 1 at post baseline visit. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity. |
Countries
Austria, Bulgaria, Canada, France, Germany, Hungary, Netherlands, Poland, Romania, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to anrukinzumab (PF-05230917) intravenous infusion over 1 hour on Day 1, Week 2, 4, 8 and 12. | 21 |
| Anrukinzumab 200 mg Anrukinzumab (PF-05230917) 200 milligram (mg) intravenous infusion over 1 hour on Day 1, Week 2, 4, 8 and 12. | 21 |
| Anrukinzumab 400 mg Anrukinzumab (PF-05230917) 400 mg intravenous infusion over 1 hour on Day 1, Week 2, 4, 8 and 12. | 21 |
| Anrukinzumab 600 mg Anrukinzumab (PF-05230917) 600 mg intravenous infusion over 1 hour on Day 1, Week 2, 4, 8 and 12. | 21 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 | 0 | 5 |
| Overall Study | Lack of Efficacy | 3 | 2 | 2 | 1 |
| Overall Study | Medication error without adverse event | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 2 |
| Overall Study | Site Closed | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 2 | 5 |
Baseline characteristics
| Characteristic | Placebo | Anrukinzumab 200 mg | Anrukinzumab 400 mg | Anrukinzumab 600 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.6 years STANDARD_DEVIATION 14.5 | 37.5 years STANDARD_DEVIATION 10.4 | 46.3 years STANDARD_DEVIATION 12.9 | 37.0 years STANDARD_DEVIATION 11.5 | 39.4 years STANDARD_DEVIATION 12.8 |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 7 Participants | 10 Participants | 35 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 14 Participants | 11 Participants | 49 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 | 12 / 21 | 18 / 21 | 13 / 21 | 15 / 21 |
| serious Total, serious adverse events | 4 / 21 | 4 / 21 | 2 / 21 | 4 / 21 |
Outcome results
Primary
Fold Change From Baseline in Fecal Calprotectin at Week 14
The fold change from baseline in fecal calprotectin at Week 14, is the ratio of the measurement of fecal calprotectin at Week 14 to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at Week 14.
Time frame: Baseline, Week 14
Population: Modified Intent to Treat (mITT: all randomized participants who received greater than or equal to \[\>=\] 1 dose study drug); Data as Observed (DAO: all mITT participants with all data needed for calculation of specified endpoint). Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Fold Change From Baseline in Fecal Calprotectin at Week 14 | 0.41 fold change |
| Anrukinzumab 200 mg | Fold Change From Baseline in Fecal Calprotectin at Week 14 | 0.29 fold change |
| Anrukinzumab 400 mg | Fold Change From Baseline in Fecal Calprotectin at Week 14 | 0.79 fold change |
| Anrukinzumab 600 mg | Fold Change From Baseline in Fecal Calprotectin at Week 14 | 1.24 fold change |
80% CI: [0.225, 0.766]
80% CI: [0.187, 0.446]
80% CI: [0.517, 1.203]
80% CI: [0.794, 1.949]
Comparison: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.53280% CI: [0.329, 1.472]ANCOVA
Comparison: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.2780% CI: [0.9, 4.013]ANCOVA
Comparison: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.066680% CI: [1.403, 6.409]ANCOVA
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab
Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported.
Time frame: Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2
Population: All participants with evaluable PK results were included in PK population. PK samples with time deviation \>20% from nominal time were excluded from statistical summary and PK analysis. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab | 8346000 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 3622500 |
| Anrukinzumab 200 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab | 14670000 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 6055800 |
| Anrukinzumab 400 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab | 24430000 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 7657300 |
Secondary
Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12
The fold change from baseline in fecal calprotectin at post-baseline visit, is the ratio of the measurement of fecal calprotectin at post-baseline visit to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at post-baseline visit.
Time frame: Baseline, Week 2, 4, 8, 12
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in mITT population; n signifies participants in mITT DAO population for specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold Change at Week 2 (n=15, 17, 18, 13) | 0.70 fold change |
| Placebo | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 4 (n=14, 18, 19, 16) | 0.92 fold change |
| Placebo | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 12 (n=9, 13, 14, 11) | 0.64 fold change |
| Placebo | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 8 (n=10, 16, 17, 16) | 0.78 fold change |
| Anrukinzumab 200 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold Change at Week 2 (n=15, 17, 18, 13) | 0.81 fold change |
| Anrukinzumab 200 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 4 (n=14, 18, 19, 16) | 0.47 fold change |
| Anrukinzumab 200 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 8 (n=10, 16, 17, 16) | 0.36 fold change |
| Anrukinzumab 200 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 12 (n=9, 13, 14, 11) | 0.19 fold change |
| Anrukinzumab 400 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 8 (n=10, 16, 17, 16) | 1.14 fold change |
| Anrukinzumab 400 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold Change at Week 2 (n=15, 17, 18, 13) | 0.71 fold change |
| Anrukinzumab 400 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 12 (n=9, 13, 14, 11) | 0.96 fold change |
| Anrukinzumab 400 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 4 (n=14, 18, 19, 16) | 0.92 fold change |
| Anrukinzumab 600 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold Change at Week 2 (n=15, 17, 18, 13) | 0.77 fold change |
| Anrukinzumab 600 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 8 (n=10, 16, 17, 16) | 0.52 fold change |
| Anrukinzumab 600 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 4 (n=14, 18, 19, 16) | 0.55 fold change |
| Anrukinzumab 600 mg | Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 | Fold change at Week 12 (n=9, 13, 14, 11) | 0.67 fold change |
Comparison: Week 2: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.466, 1.048]
Comparison: Week 2: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.552, 1.185]
Comparison: Week 2: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.488, 1.027]
Comparison: Week 2: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.5, 1.195]
Comparison: Week 4: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.631, 1.328]
Comparison: Week 4: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.339, 0.655]
Comparison: Week 4: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.669, 1.269]
Comparison: Week 4: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.388, 0.779]
Comparison: Week 8: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.454, 1.331]
Comparison: Week 8: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.236, 0.553]
Comparison: Week 8: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.757, 1.722]
Comparison: Week 8: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.338, 0.788]
Comparison: Week 12: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.374, 1.084]
Comparison: Week 12: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.122, 0.297]
Comparison: Week 12: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.623, 1.465]
Comparison: Week 12: LS mean and CI were based on back log-transformation of those from the ANCOVA model.80% CI: [0.411, 1.076]
Comparison: Week 2: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.735280% CI: [0.663, 2.021]ANCOVA
Comparison: Week 2: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.975480% CI: [0.586, 1.753]ANCOVA
Comparison: Week 2: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.827780% CI: [0.609, 2.008]ANCOVA
Comparison: Week 4: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.088580% CI: [0.313, 0.846]ANCOVA
Comparison: Week 4: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.985680% CI: [0.617, 1.644]ANCOVA
Comparison: Week 4: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.199680% CI: [0.361, 1]ANCOVA
Comparison: Week 8: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.155380% CI: [0.233, 0.926]ANCOVA
Comparison: Week 8: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.463380% CI: [0.748, 2.882]ANCOVA
Comparison: Week 8: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.440980% CI: [0.335, 1.316]ANCOVA
Comparison: Week 12: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.028380% CI: [0.15, 0.598]ANCOVA
Comparison: Week 12: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.443480% CI: [0.758, 2.97]ANCOVA
Comparison: Week 12: P-value was calculated from ANCOVA model with terms for treatment group, baseline (in log scale).p-value: 0.937280% CI: [0.51, 2.141]ANCOVA
Secondary
Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
Time frame: Pre-dose to end of the dosing interval after Day 1, Week 12
Population: All participants with evaluable pharmacokinetic (PK) results were included in PK population. PK samples with time deviation greater than (\>) 20 percent (%) from nominal time were excluded from statistical summary and PK analysis. Number of participants analyzed = participants in PK population; n = evaluable participants at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Day 1 (n=19, 20, 20) | 54480 nanogram/milliliter (ng/mL) | Standard Deviation 15027 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Week 12 (n=15, 16, 13) | 68270 nanogram/milliliter (ng/mL) | Standard Deviation 34360 |
| Anrukinzumab 200 mg | Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Day 1 (n=19, 20, 20) | 101200 nanogram/milliliter (ng/mL) | Standard Deviation 36239 |
| Anrukinzumab 200 mg | Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Week 12 (n=15, 16, 13) | 121400 nanogram/milliliter (ng/mL) | Standard Deviation 43461 |
| Anrukinzumab 400 mg | Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Day 1 (n=19, 20, 20) | 182200 nanogram/milliliter (ng/mL) | Standard Deviation 64817 |
| Anrukinzumab 400 mg | Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Week 12 (n=15, 16, 13) | 197600 nanogram/milliliter (ng/mL) | Standard Deviation 80647 |
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab
Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
Time frame: Pre-dose to end of the dosing interval after Day 1, Week 12
Population: All participants with evaluable PK results were included in PK population. PK samples with time deviation \>20% from nominal time were excluded from statistical summary and PK analysis. Number of participants analyzed signifies participants in PK population; n signifies evaluable participants at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Day 1 (n=19, 20, 20) | 0.0000 ng/mL | Standard Deviation 0 |
| Placebo | Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Week 12 (n=15, 16, 13) | 13310 ng/mL | Standard Deviation 8314 |
| Anrukinzumab 200 mg | Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Day 1 (n=19, 20, 20) | 42.45 ng/mL | Standard Deviation 165.38 |
| Anrukinzumab 200 mg | Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Week 12 (n=15, 16, 13) | 22350 ng/mL | Standard Deviation 14281 |
| Anrukinzumab 400 mg | Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Day 1 (n=19, 20, 20) | 51.19 ng/mL | Standard Deviation 201.57 |
| Anrukinzumab 400 mg | Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Week 12 (n=15, 16, 13) | 31120 ng/mL | Standard Deviation 16821 |
Secondary
Number of Participants Who Discontinued From the Study Due to Adverse Events
Time frame: Baseline up to Week 32
Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Discontinued From the Study Due to Adverse Events | 4 participants |
| Anrukinzumab 200 mg | Number of Participants Who Discontinued From the Study Due to Adverse Events | 5 participants |
| Anrukinzumab 400 mg | Number of Participants Who Discontinued From the Study Due to Adverse Events | 1 participants |
| Anrukinzumab 600 mg | Number of Participants Who Discontinued From the Study Due to Adverse Events | 5 participants |
Secondary
Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody
Neutralizing antibody was not analyzed as no participant had positive ADA samples.
Time frame: Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in mITT population; n signifies participants in mITT DAO population for specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 32 (n=10, 13, 15, 6) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 8 (n=15, 17, 18, 13) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 20 (n=11, 14, 15, 7) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 16 (n=10, 15, 14, 7) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 4 (n=17, 18, 20, 18) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 12 (n=14, 15, 17, 13) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Day 1 (n=18, 20, 19, 21) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 28 (n=8, 12, 13, 7) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 24 (n=10, 12, 14, 7) | 0 participants |
| Placebo | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 14 (n=13, 14, 15, 13) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 32 (n=10, 13, 15, 6) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Day 1 (n=18, 20, 19, 21) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 12 (n=14, 15, 17, 13) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 14 (n=13, 14, 15, 13) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 16 (n=10, 15, 14, 7) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 4 (n=17, 18, 20, 18) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 8 (n=15, 17, 18, 13) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 20 (n=11, 14, 15, 7) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 24 (n=10, 12, 14, 7) | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 28 (n=8, 12, 13, 7) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 8 (n=15, 17, 18, 13) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 4 (n=17, 18, 20, 18) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 24 (n=10, 12, 14, 7) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 14 (n=13, 14, 15, 13) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 12 (n=14, 15, 17, 13) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 16 (n=10, 15, 14, 7) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 20 (n=11, 14, 15, 7) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 28 (n=8, 12, 13, 7) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 32 (n=10, 13, 15, 6) | 0 participants |
| Anrukinzumab 400 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Day 1 (n=18, 20, 19, 21) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 32 (n=10, 13, 15, 6) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 4 (n=17, 18, 20, 18) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 8 (n=15, 17, 18, 13) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 28 (n=8, 12, 13, 7) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 20 (n=11, 14, 15, 7) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 12 (n=14, 15, 17, 13) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Day 1 (n=18, 20, 19, 21) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 24 (n=10, 12, 14, 7) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 16 (n=10, 15, 14, 7) | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Week 14 (n=13, 14, 15, 13) | 0 participants |
Secondary
Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14
Mayo score is used to measure the disease activity of ulcerative colitis. Endoscopy or flexible sigmoidoscopy is a sub score of Mayo score. The score for endoscopic subscore ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for endoscopy or flexible sigmoidoscopy at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.
Time frame: Baseline, Week 14
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Worsening | 3 participants |
| Placebo | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Improvement | 6 participants |
| Placebo | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | No Change | 3 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | No Change | 5 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Improvement | 8 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Worsening | 2 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Improvement | 11 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | No Change | 5 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Worsening | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Worsening | 0 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | Improvement | 2 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 | No Change | 11 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 32 that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study drug, which occurred during the trial.
Time frame: Baseline up to Week 32
Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 15 participants |
| Anrukinzumab 200 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
| Anrukinzumab 200 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 19 participants |
| Anrukinzumab 400 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 17 participants |
| Anrukinzumab 400 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Anrukinzumab 600 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
| Anrukinzumab 600 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 17 participants |
Secondary
Plasma Decay Half-Life (t1/2) for Anrukinzumab
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
Population: All participants with evaluable PK results were included in PK population. PK samples with time deviation \>20% from nominal time were excluded from statistical summary and PK analysis. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Decay Half-Life (t1/2) for Anrukinzumab | 392.4 hours | Standard Deviation 99.107 |
| Anrukinzumab 200 mg | Plasma Decay Half-Life (t1/2) for Anrukinzumab | 470.5 hours | Standard Deviation 361.46 |
| Anrukinzumab 400 mg | Plasma Decay Half-Life (t1/2) for Anrukinzumab | 362.4 hours | Standard Deviation 111.18 |
Secondary
Systemic Clearance (CL) for Anrukinzumab
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
Population: All participants with evaluable PK results were included in PK population. PK samples with time deviation \>20% from nominal time were excluded from statistical summary and PK analysis. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Systemic Clearance (CL) for Anrukinzumab | 0.2844 liters/day | Standard Deviation 0.15918 |
| Anrukinzumab 200 mg | Systemic Clearance (CL) for Anrukinzumab | 0.3090 liters/day | Standard Deviation 0.14268 |
| Anrukinzumab 400 mg | Systemic Clearance (CL) for Anrukinzumab | 0.3789 liters/day | Standard Deviation 0.23249 |
Secondary
Total Interleukin-13 (IL-13) Level
Time frame: Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in mITT population; n signifies participants in mITT DAO population for specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Interleukin-13 (IL-13) Level | Week 12 (n=12, 14, 17, 11) | 0.8925 picogram/milliliter | Standard Deviation 1.38386 |
| Placebo | Total Interleukin-13 (IL-13) Level | Day 7 (n=7, 12, 9, 13) | 0.8991 picogram/milliliter | Standard Deviation 1.15883 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 24 (n=10, 12, 12, 8) | 1.3300 picogram/milliliter | Standard Deviation 1.41349 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 28 (n=10, 12, 13, 8) | 1.2151 picogram/milliliter | Standard Deviation 2.23797 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 32 (n=9, 12, 13, 8) | 0.4727 picogram/milliliter | Standard Deviation 0.37875 |
| Placebo | Total Interleukin-13 (IL-13) Level | Day 2 (n=21, 19, 17, 18) | 0.5980 picogram/milliliter | Standard Deviation 0.81335 |
| Placebo | Total Interleukin-13 (IL-13) Level | Day 4 (n=16, 16, 20, 15) | 0.7056 picogram/milliliter | Standard Deviation 1.29166 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 2 (n=20, 21, 19, 19) | 0.7177 picogram/milliliter | Standard Deviation 0.98373 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 4 (n=18, 21, 19, 17) | 0.8949 picogram/milliliter | Standard Deviation 1.47538 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 8 (n=16, 18, 18, 15) | 0.7310 picogram/milliliter | Standard Deviation 1.09524 |
| Placebo | Total Interleukin-13 (IL-13) Level | Baseline (n=15, 21, 20, 19) | 0.6247 picogram/milliliter | Standard Deviation 0.97041 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 14 (n=12, 14, 16, 13) | 1.0545 picogram/milliliter | Standard Deviation 1.15526 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 16 (n=10, 12, 12, 7) | 0.5054 picogram/milliliter | Standard Deviation 0.29982 |
| Placebo | Total Interleukin-13 (IL-13) Level | Week 20 (n=8, 15, 15, 8) | 1.5140 picogram/milliliter | Standard Deviation 1.8237 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 16 (n=10, 12, 12, 7) | 15.0002 picogram/milliliter | Standard Deviation 40.41488 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 2 (n=20, 21, 19, 19) | 16.6373 picogram/milliliter | Standard Deviation 54.71391 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 28 (n=10, 12, 13, 8) | 0.9936 picogram/milliliter | Standard Deviation 0.75719 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Baseline (n=15, 21, 20, 19) | 1.6231 picogram/milliliter | Standard Deviation 2.9519 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 12 (n=12, 14, 17, 11) | 19.3543 picogram/milliliter | Standard Deviation 52.0088 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 20 (n=8, 15, 15, 8) | 9.8396 picogram/milliliter | Standard Deviation 25.99516 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 4 (n=18, 21, 19, 17) | 15.1244 picogram/milliliter | Standard Deviation 43.76893 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Day 2 (n=21, 19, 17, 18) | 3.6373 picogram/milliliter | Standard Deviation 4.695 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 8 (n=16, 18, 18, 15) | 21.4964 picogram/milliliter | Standard Deviation 72.31269 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 32 (n=9, 12, 13, 8) | 1.0548 picogram/milliliter | Standard Deviation 0.80675 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Day 7 (n=7, 12, 9, 13) | 15.6742 picogram/milliliter | Standard Deviation 34.90836 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 14 (n=12, 14, 16, 13) | 33.6697 picogram/milliliter | Standard Deviation 110.9546 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Week 24 (n=10, 12, 12, 8) | 3.0140 picogram/milliliter | Standard Deviation 3.23912 |
| Anrukinzumab 200 mg | Total Interleukin-13 (IL-13) Level | Day 4 (n=16, 16, 20, 15) | 7.7698 picogram/milliliter | Standard Deviation 9.02951 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 2 (n=20, 21, 19, 19) | 17.7895 picogram/milliliter | Standard Deviation 18.53571 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 28 (n=10, 12, 13, 8) | 2.8005 picogram/milliliter | Standard Deviation 2.67967 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 14 (n=12, 14, 16, 13) | 20.0044 picogram/milliliter | Standard Deviation 37.36283 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 32 (n=9, 12, 13, 8) | 1.9379 picogram/milliliter | Standard Deviation 1.99196 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Day 2 (n=21, 19, 17, 18) | 6.6673 picogram/milliliter | Standard Deviation 7.29515 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 20 (n=8, 15, 15, 8) | 7.4261 picogram/milliliter | Standard Deviation 8.00205 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Day 7 (n=7, 12, 9, 13) | 16.6700 picogram/milliliter | Standard Deviation 16.73533 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 16 (n=10, 12, 12, 7) | 16.4423 picogram/milliliter | Standard Deviation 24.5491 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 4 (n=18, 21, 19, 17) | 17.1853 picogram/milliliter | Standard Deviation 15.00105 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 8 (n=16, 18, 18, 15) | 16.8200 picogram/milliliter | Standard Deviation 15.4702 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Baseline (n=15, 21, 20, 19) | 1.2900 picogram/milliliter | Standard Deviation 2.07219 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Day 4 (n=16, 16, 20, 15) | 12.3410 picogram/milliliter | Standard Deviation 11.84611 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 12 (n=12, 14, 17, 11) | 22.4335 picogram/milliliter | Standard Deviation 27.04635 |
| Anrukinzumab 400 mg | Total Interleukin-13 (IL-13) Level | Week 24 (n=10, 12, 12, 8) | 6.3665 picogram/milliliter | Standard Deviation 7.85116 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 2 (n=20, 21, 19, 19) | 21.5021 picogram/milliliter | Standard Deviation 27.03784 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 12 (n=12, 14, 17, 11) | 6.8461 picogram/milliliter | Standard Deviation 4.19321 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 32 (n=9, 12, 13, 8) | 2.4725 picogram/milliliter | Standard Deviation 2.54141 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Baseline (n=15, 21, 20, 19) | 0.7525 picogram/milliliter | Standard Deviation 1.59494 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Day 7 (n=7, 12, 9, 13) | 11.3600 picogram/milliliter | Standard Deviation 16.79136 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 28 (n=10, 12, 13, 8) | 3.1724 picogram/milliliter | Standard Deviation 2.15647 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Day 4 (n=16, 16, 20, 15) | 10.1349 picogram/milliliter | Standard Deviation 10.24068 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 24 (n=10, 12, 12, 8) | 3.0913 picogram/milliliter | Standard Deviation 1.99098 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Day 2 (n=21, 19, 17, 18) | 5.0474 picogram/milliliter | Standard Deviation 4.97368 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 16 (n=10, 12, 12, 7) | 3.7570 picogram/milliliter | Standard Deviation 2.91709 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 4 (n=18, 21, 19, 17) | 8.7807 picogram/milliliter | Standard Deviation 5.39145 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 14 (n=12, 14, 16, 13) | 8.9492 picogram/milliliter | Standard Deviation 6.33317 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 8 (n=16, 18, 18, 15) | 6.8027 picogram/milliliter | Standard Deviation 3.4481 |
| Anrukinzumab 600 mg | Total Interleukin-13 (IL-13) Level | Week 20 (n=8, 15, 15, 8) | 4.1745 picogram/milliliter | Standard Deviation 2.8422 |
Secondary
Volume of Distribution (Vz) for Anrukinzumab
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
Population: All participants with evaluable PK results were included in PK population. PK samples with time deviation \>20% from nominal time were excluded from statistical summary and PK analysis. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Volume of Distribution (Vz) for Anrukinzumab | 5.726 liters | Standard Deviation 2.5057 |
| Anrukinzumab 200 mg | Volume of Distribution (Vz) for Anrukinzumab | 9.704 liters | Standard Deviation 13.186 |
| Anrukinzumab 400 mg | Volume of Distribution (Vz) for Anrukinzumab | 6.143 liters | Standard Deviation 2.1013 |
Other Pre-specified
Change From Baseline in Total Mayo Score at Week 14
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy \[endoscopy\] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.
Time frame: Baseline, Week 14
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Total Mayo Score at Week 14 | -1.32 unit on a scale |
| Anrukinzumab 200 mg | Change From Baseline in Total Mayo Score at Week 14 | -2.28 unit on a scale |
| Anrukinzumab 400 mg | Change From Baseline in Total Mayo Score at Week 14 | -2.30 unit on a scale |
| Anrukinzumab 600 mg | Change From Baseline in Total Mayo Score at Week 14 | -0.79 unit on a scale |
80% CI: [-2.332, -0.3]
80% CI: [-3.19, -1.374]
80% CI: [-3.178, -1.419]
80% CI: [-1.761, 0.19]
Comparison: P-value was analyzed from ANCOVA model with terms for treatment group and baseline.p-value: 0.363980% CI: [-2.335, 0.403]ANCOVA
Comparison: P-value was analyzed from ANCOVA model with terms for treatment group and baseline.p-value: 0.344680% CI: [-2.32, 0.355]ANCOVA
Comparison: P-value was analyzed from ANCOVA model with terms for treatment group and baseline.p-value: 0.628580% CI: [-0.884, 1.945]ANCOVA
Other Pre-specified
Clinical Remission Rate at Week 14
Clinical remission rate is defined as percentage of participants with a total Mayo score less than or equal to 2, with no individual subscore greater than 1 at post baseline visit. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.
Time frame: Week 14
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Clinical Remission Rate at Week 14 | 16.67 percentage of participants |
| Anrukinzumab 200 mg | Clinical Remission Rate at Week 14 | 33.33 percentage of participants |
| Anrukinzumab 400 mg | Clinical Remission Rate at Week 14 | 18.75 percentage of participants |
| Anrukinzumab 600 mg | Clinical Remission Rate at Week 14 | 0.00 percentage of participants |
80% CI: [7.14, 34.22]
80% CI: [20.08, 49.88]
80% CI: [9.4, 33.92]
80% CI: [0, 11.22]
Comparison: Two-sided p-value was calculated by Fisher's exact test.p-value: 0.408280% CI: [-5.33, 35.76]Fisher Exact
Comparison: Two-sided p-value was calculated by Fisher's exact test.p-value: 180% CI: [-17.8, 19.99]Fisher Exact
Comparison: Two-sided p-value was calculated by Fisher's exact test.p-value: 0.2280% CI: [-34.22, -1.95]Fisher Exact
Other Pre-specified
Clinical Response Rate at Week 14
Clinical response rate is defined as percentage of participants with at least 3 point decrease from baseline in total Mayo score with at least 30% change along with 1 point decrease from baseline or absolute score of 0 or 1 in rectal bleeding. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy \[endoscopy\] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.
Time frame: Week 14
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Clinical Response Rate at Week 14 | 41.67 percentage of participants |
| Anrukinzumab 200 mg | Clinical Response Rate at Week 14 | 60.00 percentage of participants |
| Anrukinzumab 400 mg | Clinical Response Rate at Week 14 | 50.00 percentage of participants |
| Anrukinzumab 600 mg | Clinical Response Rate at Week 14 | 15.38 percentage of participants |
80% CI: [25.53, 59.81]
80% CI: [43.59, 74.43]
80% CI: [34.74, 65.26]
80% CI: [6.58, 31.96]
Comparison: Two-sided p-value was calculated by Fisher's exact test.p-value: 0.449580% CI: [-6.13, 39.98]Fisher Exact
Comparison: Two-sided p-value was calculated by Fisher's exact test.p-value: 0.717780% CI: [-15.37, 30.54]Fisher Exact
Comparison: Two-sided p-value was calculated by Fisher's exact test.p-value: 0.201680% CI: [-46.45, -3.15]Fisher Exact
Other Pre-specified
Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
Mayo score is used to measure the disease activity of ulcerative colitis. Rectal bleeding is a sub score of Mayo score. The score for rectal bleeding ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for rectal bleeding at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.
Time frame: Baseline, Week 14
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Improvement | 4 participants |
| Placebo | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | No Change | 6 participants |
| Placebo | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Worsening | 2 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Worsening | 1 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | No Change | 6 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Improvement | 8 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Improvement | 7 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | No Change | 6 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Worsening | 3 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Improvement | 5 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | Worsening | 1 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 | No Change | 7 participants |
Other Pre-specified
Number of Participants With Change From Baseline in Stool Frequency at Week 14
Stool frequency is a sub score of Mayo score used to measure the disease activity of ulcerative colitis. The score for stool frequency ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for stool frequency at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.
Time frame: Baseline, Week 14
Population: mITT: all randomized participants who received \>=1 dose study drug; DAO: all mITT participants with all data needed for calculation of specified endpoint. Number of Participants Analyzed signifies participants in the mITT DAO population for specified endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | No Change | 8 participants |
| Placebo | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Improvement | 4 participants |
| Placebo | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Worsening | 0 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | No Change | 4 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Improvement | 7 participants |
| Anrukinzumab 200 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Worsening | 4 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Improvement | 7 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | No Change | 8 participants |
| Anrukinzumab 400 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Worsening | 1 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Worsening | 4 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | No Change | 6 participants |
| Anrukinzumab 600 mg | Number of Participants With Change From Baseline in Stool Frequency at Week 14 | Improvement | 3 participants |