A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate The Efficacy, Safety, and Pharmacokinetics of PF-06480605 in Adult Participants With Moderate To Severe Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 246
- 试验地点
- 329
- 主要终点
- Induction Period: Percentage of Participants Who Achieved Clinical Remission at Week 14
研究概览
简要总结
This phase 2b study is designed to have all subjects go into a 12 week induction period to compare different doses of study drug against placebo. After induction is complete all subjects will receive active therapy for 40 weeks, followed by a 12 week follow up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of UC for >=3 months.
- •Participants with moderate to severe active UC as defined by a Total Mayo Score of >=6, and an endoscopic subscore of >=
- •Active disease beyond the rectum (>15 cm of active disease from the anal verge at the screening endoscopy).
- •Must have failed or been intolerant to at least one of the following class of medications: steroids, immunosuppressants, anti-TNFs, anti-integrin inhibitors, anti- IL-12/23 inhibitors, or JAK inhibitors.
排除标准
- •Participants with a diagnosis of ischemic colitis, infectious colitis, radiation colitis, microscopic colitis, indeterminate colitis, or findings suggestive of Crohn's disease (eg, skip lesions, fistulae/perianal disease, non-necrotizing granulomas, etc.).
- •Participants with an imminent need for surgery or with elective surgery scheduled to occur during the study
- •Chest Radiograph showing abnormalities: The study will accept a Chest x-ray or computed tomography scan of the chest examination performed up to 12 weeks prior to screening if available.
- •12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
- •Infected with tuberculosis, (TB): Any evidence of untreated latent or active TB infection.
- •Infected with human immunodeficiency virus, (HIV), Hepatitis B or C viruses
研究组 & 干预措施
Cohort 8
Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W
干预措施: Induction- PF-06480605 450 mg SC Q4W (Drug)
Cohort 1
Induction - Placebo SC Q4W, (sub-cutaneous every 4 weeks) Chronic- PF-06480605 50 mg SC Q4W
干预措施: Induction- Placebo SC Q4W (Other)
Cohort 1
Induction - Placebo SC Q4W, (sub-cutaneous every 4 weeks) Chronic- PF-06480605 50 mg SC Q4W
干预措施: Chronic- PF-06480605 50 mg SC Q4W (Drug)
Cohort 2
Induction - Placebo SC Q4W, Chronic- PF-06480605 150 mg SC Q4W
干预措施: Induction- Placebo SC Q4W (Other)
Cohort 2
Induction - Placebo SC Q4W, Chronic- PF-06480605 150 mg SC Q4W
干预措施: Chronic- PF-06480605 150 mg SC Q4W (Drug)
Cohort 3
Induction - Placebo SC Q4W, Chronic- PF-06480605 450 mg SC Q4W
干预措施: Chronic- PF-06480605 450 mg SC Q4W (Drug)
Cohort 4
Induction- PF-06480605 50 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W
干预措施: Induction- PF-06480605 50 mg SC Q4W (Drug)
Cohort 5
Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W
干预措施: Induction- PF-06480605 150 mg SC Q4W (Drug)
Cohort 5
Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W
干预措施: Chronic- PF-06480605 50 mg SC Q4W (Drug)
Cohort 6
Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W
干预措施: Induction- PF-06480605 150 mg SC Q4W (Drug)
Cohort 6
Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W
干预措施: Chronic- PF-06480605 150 mg SC Q4W (Drug)
Cohort 7
Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W
干预措施: Induction- PF-06480605 450 mg SC Q4W (Drug)
Cohort 9
Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 450 mg SC Q4W
干预措施: Chronic- PF-06480605 450 mg SC Q4W (Drug)
Cohort 3
Induction - Placebo SC Q4W, Chronic- PF-06480605 450 mg SC Q4W
干预措施: Induction- Placebo SC Q4W (Other)
Cohort 4
Induction- PF-06480605 50 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W
干预措施: Chronic- PF-06480605 50 mg SC Q4W (Drug)
Cohort 7
Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W
干预措施: Chronic- PF-06480605 50 mg SC Q4W (Drug)
Cohort 8
Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W
干预措施: Chronic- PF-06480605 150 mg SC Q4W (Drug)
Cohort 9
Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 450 mg SC Q4W
干预措施: Induction- PF-06480605 450 mg SC Q4W (Drug)
结局指标
主要结局
Induction Period: Percentage of Participants Who Achieved Clinical Remission at Week 14
时间窗: At Week 14
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.
Induction Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From initiation of study treatment to either first dose in the chronic period or end of safety follow-up, whichever occurs first. (Approximately 16 weeks plus 12-week safety follow-up, if applicable.)
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.
Induction Period: Number of Participants With Serious Adverse Events (SAEs)
时间窗: From initiation of study treatment to either first dose in the chronic period or end of safety follow-up, whichever occurs first. (Approximately 16 weeks plus 12-week safety follow-up, if applicable.)
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.
Induction Period: Number of Participants With AEs or SAEs Leading to Discontinuation
时间窗: From initiation of study treatment to either first dose in the chronic period or end of safety follow-up, whichever occurs first. (Approximately 16 weeks plus 12-week safety follow-up, if applicable.)
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.
Chronic Period: Number of Participants With TEAEs
时间窗: From first dose of study treatment in the chronic period to end of safety follow-up. (Approximately 40 weeks plus 12-week safety follow-up.)
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.
Chronic Period: Number of Participants With SAEs
时间窗: From first dose of study treatment in the chronic period to end of safety follow-up. (Approximately 40 weeks plus 12-week safety follow-up.)
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.
Chronic Period: Number of Participants With AEs or SAEs Leading to Discontinuation
时间窗: From first dose of study treatment in the chronic period to end of safety follow-up. (Approximately 40 weeks plus 12-week safety follow-up.)
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.
Induction Period: Percentage of Participants Who Achieved Clinical Remission at Week 14
时间窗: At Week 14
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.
Induction Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From initiation of study treatment to either first dose in the chronic period or end of safety follow-up, whichever occurs first. (Approximately 16 weeks plus 12-week safety follow-up, if applicable.)
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.
Induction Period: Number of Participants With Serious Adverse Events (SAEs)
时间窗: From initiation of study treatment to either first dose in the chronic period or end of safety follow-up, whichever occurs first. (Approximately 16 weeks plus 12-week safety follow-up, if applicable.)
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.
Induction Period: Number of Participants With AEs or SAEs Leading to Discontinuation
时间窗: From initiation of study treatment to either first dose in the chronic period or end of safety follow-up, whichever occurs first. (Approximately 16 weeks plus 12-week safety follow-up, if applicable.)
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.
Chronic Period: Number of Participants With TEAEs
时间窗: From first dose of study treatment in the chronic period to end of safety follow-up. (Approximately 40 weeks plus 12-week safety follow-up.)
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.
Chronic Period: Number of Participants With SAEs
时间窗: From first dose of study treatment in the chronic period to end of safety follow-up. (Approximately 40 weeks plus 12-week safety follow-up.)
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.
Chronic Period: Number of Participants With AEs or SAEs Leading to Discontinuation
时间窗: From first dose of study treatment in the chronic period to end of safety follow-up. (Approximately 40 weeks plus 12-week safety follow-up.)
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.
次要结局
- Induction and Chronic: Percentage of Participants Who Achieved Endoscopic Improvement(Induction Period: At Week 14; Chrnoic Period: At Week 56)
- Induction Period: Change From Baseline in Fecal Calprotectin(Baseline, Weeks 4, 8, and 12)
- Induction Period: Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)(Baseline, Weeks 4, 8, and 12)
- Induction Period: Change From Baseline in Serum Soluble TL1A (sTL1A)(Baseline, Weeks 4, 8, and 12)
- Induction Period: Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) to PF-06480605(Baseline, Weeks 4, 8, 12, 14)
- Chronic Period: Percentage of Participants Who Achieved Clinical Remission(At Week 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Clinical Remission(At Weeks 14 and 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Remission as Per FDA Definition 1 (Modified Remission 1)(At Weeks 14 and 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Endoscopic Remission(At Weeks 14 and 56)
- Chronic Period: Change From Week 14 in Serum sTL1A(Week 14 (baseline), Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Change From Baseline in Fecal Calprotectin Through the End of Study(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, and 64)
- Change From Baseline in hsCRP Through the End of Study(Baseline, Weeks 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Change From Baseline in Serum sTL1A Through the End of Study(Baseline, Weeks 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Chronic Period: Number of Participants With ADA and NAbs to PF-06480605(Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64)
- Induction and Chronic: Trough Concentration (Ctrough) of PF-06480605(Induction Period: 30 mins postdose on Day 1, Weeks 4, 8, 12 and 14; Chronic Period: 30 mins postdose on Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48; End of Treatment (EOT) (Week 52) and Follow-up (FU) Visits 1 (Week 56), 2 (Week 60) and 3 (Week 64))
- Induction Period: Change From Baseline in Fecal Calprotectin(Baseline, Weeks 4, 8, and 12)
- Induction Period: Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)(Baseline, Weeks 4, 8, and 12)
- Induction Period: Change From Baseline in Serum Soluble TL1A (sTL1A)(Baseline, Weeks 4, 8, and 12)
- Change From Baseline in Serum sTL1A Through the End of Study(Baseline, Weeks 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Induction and Chronic: Percentage of Participants Who Achieved Remission as Per Food and Drug Administration (FDA) Definition 1 (Modified Remission 1)(Induction Period: At Week 14; Chronic Period: At Week 56)
- Induction and Chronic: Percentage of Participants Who Achieved Remission as Per FDA Definition 2 (Modified Remission 2)(Induction Period: At Week 14; Chronic Period: At Week 56)
- Induction and Chronic: Percentage of Participants Who Achieved Endoscopic Improvement(Induction Period: At Week 14; Chrnoic Period: At Week 56)
- Induction and Chronic: Percentage of Participants Who Achieved Endoscopic Remission(Induction Period: At Week 14; Chronic Period: At Week 56)
- Change From Baseline in hsCRP Through the End of Study(Baseline, Weeks 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Induction Period: Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) to PF-06480605(Baseline, Weeks 4, 8, 12, 14)
- Chronic Period: Percentage of Participants Who Achieved Clinical Remission(At Week 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Clinical Remission(At Weeks 14 and 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Remission as Per FDA Definition 1 (Modified Remission 1)(At Weeks 14 and 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Remission as Per FDA Definition 2 (Modified Remission 2)(At Weeks 14 and 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Endoscopic Improvement(At Weeks 14 and 56)
- Chronic Period: Percentage of Participants Who Achieved Sustained Endoscopic Remission(At Weeks 14 and 56)
- Chronic Period: Change From Week 16 in Fecal Calprotectin(Week 16 (baseline), Weeks 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, and 64)
- Chronic Period: Change From Week 14 in hsCRP(Week 14 (baseline), Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Chronic Period: Change From Week 14 in Serum sTL1A(Week 14 (baseline), Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64)
- Change From Baseline in Fecal Calprotectin Through the End of Study(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, and 64)
- Chronic Period: Number of Participants With ADA and NAbs to PF-06480605(Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64)