Clinical Trials List
Protocol NumberB7541002
NCT Number(ClinicalTrials.gov Identfier)NCT02840721
2016-07-21 - 2018-11-03
Phase II
Terminated3
ICD-10K51
Ulcerative colitis
ICD-9556.9
Ulcerative colitis, unspecified
A PHASE 2A, MULTICENTER, SINGLE ARM, OPEN- LABEL, TWO-STAGE, STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06480605 IN SUBJECTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS
-
Trial Applicant
ICON Clinical Research Pte Ltd
-
Sponsor
Pfizer Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2023/03/10
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Kaohsiung Municipal Gangshan Hospital
Chairman/Global PI
吳登強
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- Chien-Yu Lu Digestive System Department
- Huang-Ming Hu Digestive System Department
- Wen-Hung Hsu Digestive System Department
- HSIANG YAO SHIH Digestive System Department
- Yu-Chung Su Digestive System Department
- Fang-Jung Yu Yu Digestive System Department
- Chao-Hung Kuo Digestive System Department
- I-CHEN WU Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Linkou Chang Gung Medical Foundation
Taiwan National PI
邱正堂
Co-Principal Investigator
- 林淳榮 Digestive System Department
- 陳聰興 Digestive System Department
- Wen-Sy Tsai Division of Colorectal Surgery
- 何玉彬 Digestive System Department
- Chia-Jung Kuo Digestive System Department
- 林蔚然 Digestive System Department
- Cheng-Yu Lin Digestive System Department
- 許振銘 Digestive System Department
- 林偉彬 Digestive System Department
- Puo-Hsien Le Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
ulcerative colitis
Objectives
The purpose of this study is to evaluate the safety, tolerability, and efficacy of PF-06480605 in subjects with moderate to severe ulcerative colitis.
Test Drug
PF-06480605
Active Ingredient
PF-06480605
Dosage Form
Injection
Dosage
100 mg
Endpoints
Primary Outcome Measures :
Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events [ Time Frame: Day 1 up to final onsite visit (Week 26) ]
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.
Number of Participants With Laboratory Abnormalities [ Time Frame: Day 1 up to final onsite visit (Week 26) ]
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).
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria [ Time Frame: Baseline up to final onsite visit (Week 26) ]
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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria [ Time Frame: Baseline up to final onsite visit (Week 26) ]
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.
Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set [ Time Frame: Week 14 ]
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).
Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events [ Time Frame: Day 1 up to final onsite visit (Week 26) ]
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.
Number of Participants With Laboratory Abnormalities [ Time Frame: Day 1 up to final onsite visit (Week 26) ]
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).
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria [ Time Frame: Baseline up to final onsite visit (Week 26) ]
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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria [ Time Frame: Baseline up to final onsite visit (Week 26) ]
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.
Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set [ Time Frame: Week 14 ]
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).
Inclution Criteria
Inclusion Criteria:
Male or female subjects between ≥ 18 and ≤ 75 years of age at the time of informed consent
Male subjects able to father children and female subjects of childbearing potential must agree to use two highly effective methods of contraception throughout the study and until the Week 26 visit
Diagnosis of ulcerative colitis for ≥ 4 months
Subjects with moderate to severe active ulcerative colitis as defined by screening colonoscopy with total Mayo score of ≥ 6, with rectal bleeding subscore of ≥ 1, and an endoscopic subscore of ≥ 2 on the Mayo
Active disease beyond the rectum (> 15 cm of active disease at the screening colonoscopy)
Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for ulcerative colitis such as: Steroids; Immunosuppressants (AZA, 6-MP, or MTX); Anti -TNF inhibitors (eg, infliximab, adalimumab, or golimumab); Anti-integrin inhibitors (eg, vedolizumab).
Subjects currently receiving the following treatment are eligible provided they have been on stable doses of Oral 5-ASA or sulfasalazine for at least 4 weeks prior to baseline; oral corticosteroids stable dose for at least 2 weeks prior to baseline; 6-MP or AZA stable dose for 8 weeks prior to baseline.
Male or female subjects between ≥ 18 and ≤ 75 years of age at the time of informed consent
Male subjects able to father children and female subjects of childbearing potential must agree to use two highly effective methods of contraception throughout the study and until the Week 26 visit
Diagnosis of ulcerative colitis for ≥ 4 months
Subjects with moderate to severe active ulcerative colitis as defined by screening colonoscopy with total Mayo score of ≥ 6, with rectal bleeding subscore of ≥ 1, and an endoscopic subscore of ≥ 2 on the Mayo
Active disease beyond the rectum (> 15 cm of active disease at the screening colonoscopy)
Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for ulcerative colitis such as: Steroids; Immunosuppressants (AZA, 6-MP, or MTX); Anti -TNF inhibitors (eg, infliximab, adalimumab, or golimumab); Anti-integrin inhibitors (eg, vedolizumab).
Subjects currently receiving the following treatment are eligible provided they have been on stable doses of Oral 5-ASA or sulfasalazine for at least 4 weeks prior to baseline; oral corticosteroids stable dose for at least 2 weeks prior to baseline; 6-MP or AZA stable dose for 8 weeks prior to baseline.
Exclusion Criteria
Exclusion Criteria:
Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or Crohn's Disease. Subjects with clinical findings suggestive of Crohn's disease (eg, fistulae, granulomas on biopsy) are also excluded.
Subjects with colonic dysplasia or neoplasia, toxic megacolon, primary sclerosing cholangitis, known colonic stricture, history of colonic or small bowel stoma, history of colonic or small bowel obstruction or resection
Presence of active enteric infections (positive stool culture and sensitivity)
Known history of HIV based on documented history with positive serological test, or positive HIV serologic test at screening
Presence of a transplanted organ
Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence);
Acute coronary syndrome (eg., myocardial infarction, unstable angina pectoris);
Any history of cerebrovascular disease within 24 weeks before screening;
Subject with current or a history of QT prolongation
Class III or Class IV heart failure
Prior evidence of liver injury or toxicity due to methotrexate
Abnormality in hematology and/or chemistry profiles during screening (as detailed in the protocol)
Subjects receiving the following therapies within the designated time period:
> 9 mg/day of oral budesonide or >20 mg/day prednisone or equivalent within 2 weeks prior to baseline
IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline
Biologics including anti-TNF inhibitors as described: Infliximab, Adalimumab, or Golimumab within 8 weeks prior to baseline
Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline
Other investigational procedures or products, or live attenuated vaccine within 30 days prior to baseline.
Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse
Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or Crohn's Disease. Subjects with clinical findings suggestive of Crohn's disease (eg, fistulae, granulomas on biopsy) are also excluded.
Subjects with colonic dysplasia or neoplasia, toxic megacolon, primary sclerosing cholangitis, known colonic stricture, history of colonic or small bowel stoma, history of colonic or small bowel obstruction or resection
Presence of active enteric infections (positive stool culture and sensitivity)
Known history of HIV based on documented history with positive serological test, or positive HIV serologic test at screening
Presence of a transplanted organ
Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence);
Acute coronary syndrome (eg., myocardial infarction, unstable angina pectoris);
Any history of cerebrovascular disease within 24 weeks before screening;
Subject with current or a history of QT prolongation
Class III or Class IV heart failure
Prior evidence of liver injury or toxicity due to methotrexate
Abnormality in hematology and/or chemistry profiles during screening (as detailed in the protocol)
Subjects receiving the following therapies within the designated time period:
> 9 mg/day of oral budesonide or >20 mg/day prednisone or equivalent within 2 weeks prior to baseline
IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline
Biologics including anti-TNF inhibitors as described: Infliximab, Adalimumab, or Golimumab within 8 weeks prior to baseline
Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline
Other investigational procedures or products, or live attenuated vaccine within 30 days prior to baseline.
Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse
The Estimated Number of Participants
-
Taiwan
3 participants
-
Global
40 participants
