The purpose of this study is to evaluate the safety, tolerability, and efficacy of PF-06480605 in subjects with moderate to severe ulcerative colitis.
This is a Phase 2a, single arm, two-stage study in subjects with moderate to severe ulcerative colitis. Subjects will receive 500 mg of PF-06480605 intravenously every 2 weeks for a total of 7 doses. Blood, stool, and tissue samples will be collected at various time points throughout the study to evaluate safety, tolerability, efficacy, pharmacokinetics, and immunogenicity. Duration of participation for subjects will be approximately 8 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
PF-06480605 500 mg IV Q2W x 7 Doses
Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious AE (SAE) was any untoward medical occurrence at any dose that (1) resulted in death; (2) was life-threatening (immediate risk of death); (3) required inpatient hospitalization or prolongation of existing hospitalization; (4) resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) resulted in congenital anomaly/birth defect. A treatment-emergent AE (TEAE) was defined as an event that emerged during treatment having been absent pre-treatment, or worsened relative to the pre-treatment state. Causality to study treatment was determined by the investigator.
Time frame: Day 1 up to final onsite visit (Week 26)
Number of Participants With Laboratory Abnormalities
The following parameters were evaluated: hematology (hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, and prothrombin time), clinical chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, glucose, and creatine kinase), and urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and bacteria).
Time frame: Day 1 up to final onsite visit (Week 26)
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Sitting blood pressure was measured with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mm Hg). The same size BP cuff which had been properly sized and calibrated was used to measure BP each time. Number of participants with vital signs data meeting pre-specified criteria is presented.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Surgery Center of Aventura
Aventura, Florida, United States
Venture Ambulatory Surgical Center
North Miami Beach, Florida, United States
FQL Research, LLC
Pembroke Pines, Florida, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, United States
NYU Langone Long Island Clinical Research Associates
Great Neck, New York, United States
NYU Langone Nassau Gastroenterology Associates
Great Neck, New York, United States
New York Presbyterian Hospital-Weill Cornell Medical College
New York, New York, United States
Weill Cornell Medical College
New York, New York, United States
Weill Cornell Medicine
New York, New York, United States
...and 18 more locations
Time frame: Baseline up to final onsite visit (Week 26)
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria
All scheduled 12-lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Number of participants with ECG data meeting pre-specified criteria is presented.
Time frame: Baseline up to final onsite visit (Week 26)
Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set
Endoscopic improvement at Week 14 was defined as Mayo endoscopic sub-score of 0 or 1, and without friability. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2=3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Percentage of Participants Achieving Remission at Week 14 - Full Analysis Set
Remission: total Mayo score \<=2 with no individual subscore \>1. Mayo scoring system was used to assess ulcerative colitis activity (range: 0 to 12, calculated as sum of 4 subscores, higher scores indicating more severe disease). The 4 subscores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on modified endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, no friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Percentage of Participants Achieving Remission at Week 14 - Per Protocol Analysis Set
Remission: total Mayo score \<=2 with no individual subscore \>1. Mayo scoring system was used to assess ulcerative colitis activity (range: 0 to 12, calculated as sum of 4 subscores, higher scores indicating more severe disease). The 4 subscores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on modified endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, no friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Percentage of Participants Achieving Endoscopic Remission at Week 14 - Full Analysis Set
Endoscopic remission at Week 14 was defined as Mayo endoscopic sub-score of 0. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Maximum Serum Concentration (Cmax) of PF-06480605
Maximum serum concentration (Cmax) of PF-06480605 was observed directly from data.
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Average Serum Concentration (Cav) of PF-06480605
Average serum concentration (Cav) of PF-06480605 was calculated as AUCtau/tau, where tau was the dosing interval (tau=14 days), and AUCtau was the area under the concentration-time profile from time 0 to time tau.
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Lowest Serum Concentration (Cmin) of PF-06480605
Lowest serum concentration (Cmin) of PF-06480605 was observed directly from data.
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Area Under the Concentration-time Profile From Time Zero to Time Tau (AUCtau) of PF-06480605
AUCtau of PF-06480605 was calculated using linear/log trapezoidal method; tau was the dosing interval (=14 days).
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Percentage of Participants Who Developed Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Serum samples were analyzed using a new ADA assay with acid pre-treatment followed by a more drug-tolerant cell-based NAb assay. For ADA assay with acid pre-treatment, the sample was deemed positive if log titer \>=1.30; for cell-based NAb assay, the sample was deemed positive if log titer \>=0.699.
Time frame: Day 1 up to final onsite visit (Week 26)
Change From Baseline in Fecal Calprotectin
Fecal calprotectin has been used to detect intestinal inflammation (colitis or enteritis) and can serve as a biomarker for inflammatory bowel diseases. Elevated fecal calprotectin levels indicate migration of neutrophils into the intestinal mucosa, which occurs during intestinal inflammation.
Time frame: Baseline, Weeks 2, 8, 12 and 26
Change From Baseline in High Sensitivity C-reactive Protein (HsCRP)
HsCRP is used mainly as a marker of inflammation.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26
Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A)
TL1A is a member of the tumor necrosis factor (TNF) family of cytokines. The investigational product of this study PF-06480605 is a fully human neutralizing antibody against TL1A.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26