Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission.

Twelve (12) lead ECGs were collected. All scheduled ECGs were performed after the participants had rested quietly for at least 10 minutes in a supine position. When the timing of these measurements coincided with a blood collection, the ECG was obtained prior to the nominal time of the blood collection, blood pressure, and pulse rate. ECG data were analyzed as per pre-specified categories. PR=pulse rate; QTc=QT interval corrected for heart rate; QTcF=QTc corrected using Fridericia's formula.

Time frame: From baseline through Week 16

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Single sitting blood pressure (BP), pulse rate, and temperature were measured. At Day 1 and Week 1, BP and pulse were collected approximately 30 minutes prior to dosing, approximately 30 minutes post dosing and approximately 1 hour post dosing. For participants with no safety issues (eg, severe injection site reactions, severe elevations BP and/or pulse), BP and pulse were collected approximately 30 minutes prior to dosing and approximately 30 minutes post dosing from Weeks 2-16. Vital signs were analyzed as per pre-specified categories.

Time frame: From baseline through Week 16

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

The laboratory tests as defined in the protocol, including hematology, chemistry, urinalysis and other, were performed. Baseline was defined as the last measurement prior to first dosing (Day 1).

Time frame: From baseline through Week 16

Population: All participants with at least one observation of the given laboratory test while on study treatment or during lag time (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were treatment-emergent AEs. An serious adverse event (SAE) is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the participant or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment.

Time frame: Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were treatment-emergent AEs. An SAE is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the participant or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment. Treatment-related AEs were also determined by the investigator.

Time frame: Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) with endoscopic subscore = 0 or 1 (where any friability was scored as a mayo endoscopic subscore of 2), stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0. Participants with missing values were handled by observed case approach (the missing data were used as is). The percentage of participants achieving modified clinical remission was calculated based on the number of participants with observed data.

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) with endoscopic subscore = 0 or 1 (where any friability was scored as a mayo endoscopic subscore of 2), stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0. Participants with missing values were handled by treatment failure approach (participants who had missing value for any reasons were considered as treatment failures).

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) \<=2, no individual subscore \>1, traditional endoscopic subscore \<=1 (where mild friability was scored as of 1; moderate or severe friability was scored as 2) and rectal bleeding subscore=0. Participants with missing values were handled by observed case approach (the missing data were used as is). The percentage of participants achieving modified clinical remission was calculated based on the number of participants with observed data.

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) \<=2, no individual subscore \>1, traditional endoscopic subscore \<=1 (where mild friability was scored as of 1; moderate or severe friability was scored as 2) and rectal bleeding subscore=0. Participants with missing values were handled by treatment failure approach (participants who had missing value for any reasons were considered as treatment failures).

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Robart's histology index is based on the Geboes scores, and the final score is obtained by the summation of four main items (chronic inflammatory infiltrate level, lamina propria neutrophils, neutrophils in the epithelium, and erosion or ulceration), which are classified from 0 (no inflammation) to 3 (severe inflammation or ulceration), yielding a final score that ranges between 0 (no inflammation) and 33 (severe inflammation or ulceration). Participants with missing values were handled by observed case approach (the missing data were used as is).

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Geboes index is a structured six-grade classification system ordered as follows: 0, structural changes (sub-grade: 0-0.3); 1, chronic inflammatory infiltrate (sub-grade: 1-1.3); 2, lamina propria neutrophils and eosinophils (sub-grade: 2A-2B.3); 3, neutrophils in epithelium (sub-grade: 3-3.3); 4, crypt destruction (sub-grade: 4-4.3); and 5, erosion and ulceration (sub-grade: 5-5.4). The final index ranges from 0 to 5.4, with low score associated with no inflammation or less inflammation and high score associated with severe inflammation or ulceration. Geboes index remission was defined as Geboes index \< 3 and Grade 3 \< 3.1 at week 12. Participants with missing values were handled by observed case approach (the missing data were used as is). The percentage of participants achieving Geboes index remission was calculated based on the number of participants with observed data.

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Clinical response is defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one-point decrease or absolute score of 0 or 1 in rectal bleeding subscore. Participants with missing values were handled by observed case approach (the missing data were used as is).

Time frame: Week 12

Population: All participants who have received at least one dose of the randomized treatment. The number of participants with observed data were 8 for the Placebo + Infliximab arm and 7 for PF-06687234 20mg + Infliximab arm. The percentage of participants achieving clinical response was calculated based on the number of participants with observed data.

The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Clinical response is defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one-point decrease or absolute score of 0 or 1 in rectal bleeding subscore. Participants with missing values were handled by treatment failure approach (participants who had missing value for any reasons were considered as treatment failures).

Time frame: Week 12

Population: All participants who have received at least one dose of the randomized treatment.

The Mayo score is determined by the summation of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 (normal) to 3 (worst). Derived partial mayo score is defined as total Mayo score excluding the endoscopic subscore (stool frequency, rectal bleeding and PGA only), ranging from 0 (normal) to 9 (the most severe). The percentages of participants with change from baseline in derived partial Mayo score of \<=2 with no individual subscore \>1 at Weeks 2, 4, 8 and 12 were calculated for this endpoint. Participants with missing values were handled by observed case approach (the missing data were used as is). Generalized Linear Mixed Model (GLMM) was used with fixed effects of treatment, visit and treatment by visit interaction.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants who have received at least one dose of the randomized treatment.

Endoscopic improvement is defined as a decrease of \>=1 point in a modified endoscopic subscore (any friability is scored as 2) or an absolute endoscopy score of \<=1 without friability. Participants with missing values were handled by observed case approach (the missing data were used as is). The percentage of participants achieving endoscopic improvement was calculated based on the number of participants with observed data.

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Endoscopic improvement is defined as a decrease of \>=1 point in a modified endoscopic subscore (any friability is scored as 2) or an absolute endoscopy score of \<=1 without friability. Participants with missing values were handled by treatment failure approach (participants who had missing value for any reasons were considered as treatment failures).

Time frame: Week 12

Population: All participants who had received at least one dose of the randomized treatment (10 each for the Placebo + Infliximab arm and the PF-06687234 20mg + Infliximab arm).

Plasma samples were analyzed for anti PF-06687234, anti PF-06687234 IL-10 neutralizing antibody (AB) and anti PF-06687234 single chain variable fragment (scFv) neutralizing AB. Samples inadvertently analyzed were excluded.

Time frame: At screening, Day 1, Weeks 3, 7, 11, 12 and 16 (prior to dosing)

Population: HAFA and NAb analyses were performed to characterize immunogenicity against PF-06687234, hence only participants who received at least one dose of PF-06687234 and with at least one post treatment HAFA determination were included.

Samples for serum PF-06687234 concentration were collected approximately 30 minutes prior to dosing. Concentration values below the lower limit of quantification were excluded when calculating the geometric mean (geometric coefficient of variation).

Time frame: Prior to dosing on Day 1 and at Weeks 1, 3, 7, 11, 12 (168 hours post dose) and 16

Population: All participants who received at least one dose of PF-06687234, had data on at least one PK concentration (above or equal to lower limit of quantification) and did not participate in PK substudy.