Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of PF-06480605 in Adults With Moderate to Severe Ulcerative Colitis (NCT NCT04090411)

A total of 246 participants with moderate to severe ulcerative colitis (UC) took part in the study at 114 investigative sites across 23 countries from 19 December 2019 to 25 October 2022. The study consisted of a 12-week induction period and a 40-week chronic therapy period.

Participants were randomized in 2:2:2:2:2:3:1:1:1 to 1 of 9 treatment sequences to receive PF-06480605 50 milligrams (mg), 150 mg, 450 mg or a matched placebo during the induction and chronic therapy periods. One participant in the PF-06480605 450 mg arm was enrolled but did not receive any treatment.

A Study to Evaluate the Efficacy and Safety of PF-06480605 in Adults With Moderate to Severe Ulcerative Colitis

Clinical remission was defined as total Mayo Score ≤2, with no individual subscore \>1. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Percentages have been rounded off to the nearest whole number.

TEAEs was defined as all events that started on or after the first dosing day and time, but before the last dose plus the lag time. An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. Results may differ from publications that used Week 14 as the end of the AE reporting timeframe.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. SAE was defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; or is a congenital anomaly/birth defect. Results may differ from publications that used Week 14 as the end of the AE reporting timeframe.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. SAE was defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; or is a congenital anomaly/birth defect. Participants who had an AE/SAE that led to study discontinuation have been reported here. Results may differ from publications that used Week 14 as the end of the AE reporting timeframe.

TEAEs was defined as all events that started on or after the first dosing day and time, but before the last dose plus the lag time. An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. Results may differ from publications that used Week 56 as the end of the AE reporting timeframe.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. SAE was defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; or is a congenital anomaly/birth defect. Results may differ from publications that used Week 56 as the end of the AE reporting timeframe.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. SAE was defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; or is a congenital anomaly/birth defect. Participants who had an AE/SAE that led to study discontinuation have been reported here. Results may differ from publications that used Week 56 as the end of the AE reporting timeframe.

Modified remission 1 was defined as an endoscopic subscore = 0 (normal or inactive disease) or 1 (mild disease), stool frequency subscore = 0 (normal number of stools per day), and rectal bleeding subscore = 0 (no blood seen) at Week 14/Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Percentages have been rounded off to the nearest whole number.

Modified remission 2 was defined as an endoscopic subscore = 0 (normal or inactive disease) or 1 (mild disease), ≥1 point decrease from baseline to achieve a stool frequency subscore = 0 (normal number of stools per day) or 1 (1 or 2 more stools than normal), and rectal bleeding subscore = 0 (no blood seen) at Week 14/Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Percentages have been rounded off to the nearest whole number.

Endoscopic improvement was defined as an endoscopic subscore of 0 (Normal or inactive disease) or 1 (Mild disease \[erythema, decreased vascular pattern, mild friability\]) at Week 14/Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3. Higher scores indicate more severe disease activity. Percentages have been rounded off to the nearest whole number.

Endoscopic remission was defined as an endoscopic subscore of 0 (Normal or inactive disease) at Week 14/Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3. Higher scores indicate more severe disease activity. Percentages have been rounded off to the nearest whole number.

Samples were considered to be positive for ADA against PF-06480605 if the titer was ≥ 60, and an ADA sample was considered to be negative if the titer was \< 60. Samples were considered to be positive for NAb against PF-06480605 if the titer was ≥ 5, and an NAb sample was considered to be negative if the titer was \< 5.

Clinical remission was defined as total Mayo Score ≤2, with no individual subscore \>1. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Percentages have been rounded off to the nearest whole number.

Clinical remission was defined as total Mayo Score ≤2, with no individual subscore \>1. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Participants with sustained clinical remission were defined as those who achieved clinical remission at both Weeks 14 and 56. Percentages have been rounded off to the nearest whole number.

Modified remission 1 was defined as an endoscopic subscore = 0 (normal or inactive disease) or 1 (mild disease), stool frequency subscore = 0 (normal number of stools per day), and rectal bleeding subscore = 0 (no blood seen) at Week 14/Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Participants with sustained clinical remission were defined as those who achieved clinical remission at both Weeks 14 and 56. Percentages have been rounded off to the nearest whole number.

Modified remission 2 was defined as an endoscopic subscore = 0 (normal or inactive disease) or 1 (mild disease), ≥1 point decrease from baseline to achieve a stool frequency subscore = 0 (normal number of stools per day) or 1 = 1 or 2 more stools than normal, and rectal bleeding subscore = 0 (no blood seen) at Week 14/Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease activity. Participants with sustained clinical remission were defined as those who achieved clinical remission at both Weeks 14 and 56. Percentages have been rounded off to the nearest whole number.

Endoscopic improvement was defined as an endoscopic subscore of 0 (Normal or inactive disease) or 1 (Mild disease \[erythema, decreased vascular pattern, mild friability\]) at both Week 14 and Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3. Higher scores indicate more severe disease activity. Participants with sustained endoscopic improvement were defined as those who achieved improvement at both Weeks 14 and 56. Percentages have been rounded off to the nearest whole number.

Endoscopic remission was defined as an endoscopic subscore of 0 (Normal or inactive disease) at both Week 14 and Week 56. Mayo Score was a tool designed to measure disease activity for UC. The score ranges from 0 - 12 and was a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and PGA subscore. Each of the four assessments was rated with a score from 0 to 3. Higher scores indicate more severe disease activity. Participants with sustained endoscopic remission were defined as those who achieved endoscopic remission at both Weeks 14 and 56. Percentages have been rounded off to the nearest whole number.