A PHASE 2A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY PROFILE OF PF-06651600 AND PF-06700841 IN SUBJECTS WITH MODERATE TO SEVERE ALOPECIA AREATA WITH A SINGLE-BLIND EXTENSION PERIOD AND A CROSS-OVER OPEN LABEL EXTENSION PERIOD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 142
- 试验地点
- 55
- 主要终点
- Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24
研究概览
简要总结
This is a Phase 2a, randomized, double blind, parallel group, multicenter study with an extension period. The study will have a maximum duration of approximately 113 weeks. This includes an up to 5 weeks Screening Period, a 24 week Treatment Period, a 4 week Drug Holiday (#1), an up to 12 month Single Blind (investigator open, sponsor open and subject blind) Extension Period, a 4 week drug holiday (#2), a 6 month Cross Over Open Label Extension Period and a 4 week Follow up Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Male or female subjects between 18 75 years of age, inclusive, at time of informed consent.
- •Must have moderate to severe alopecia areata:
排除标准
- •History of human immunodeficiency virus (HIV) or positive HIV serology at screening,
- •Infected with hepatitis B or hepatitis C viruses.
- •Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
- •Have received any of the following treatment regiments specified in the timeframes outlined below:
- •Within 6 months of first dose of study drug: Any cell depleting agents Within 12 weeks of first dose of study drug: Any studies with JAK inhibitors; Other biologics Within 8 weeks of first dose of study drug: Participation in other studies involving investigational drug(s) Within 6 weeks of first dose of study drug: Have been vaccinated with live or attenuated live vaccine.
- •Within 4 weeks of first dose of study drug: Use of oral immune suppressants; Phototherapy (NB UVB) or broad band phototherapy; Regular use (more than 2 visits per week) of a tanning booth/parlor.
- •Within 2 week of first dose of study drug: Topical treatments that could affect AA; Herbal medications with unknown properties or known beneficial effects for AA.
研究组 & 干预措施
Cohort 1
PF-06651600
干预措施: PF-06651600 (Drug)
Cohort 2
PF-06700841
干预措施: PF-06700841 (Drug)
Cohort placebo
placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24
时间窗: Baseline, Week24
SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. Score range: 0-100%. Higher score indicates more severe disease. Change from baseline is defined as the baseline value minus the value at a specific visit. Positive change from baseline signifies an improvement. Baseline is defined as the last measurement prior to first dosing (Day 1).
Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Single-Blind Extension (SBE) Period
时间窗: Week 28 up to Week 52
An AE (non-serious and serious) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent Adverse Event (TEAE). Treatment-related TEAE were determined by investigators. Arms end with "withdrawal Segment" and "retreatment segment" described the same population while in different treatment segment .The reason why count on PF-06700841 differ by 1 participant is that 1 responder directly entered the retreatment segment and skipped the withdrawal segment.
Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Cross-Over Extension (COE) Period
时间窗: COE day 1 up to end of study
An AE (non-serious and serious) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent Adverse Event (TEAE). Treatment-related TEAE were determined by investigators.
Number of Participants With Laboratory Abnormalities During SBE Period
时间窗: Week 28 up to Week 52 for non-responders and responders in the withdrawal segment, AT day 1 up to AT Week 24 for retreatment segment (AT=active treatment)
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology(Hemoglobin, Hematocrit, RBC count, Reticulocyte count, Platelet count, WBC count with differential, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes); serum chemistry (BUN and Creatinine, Cystatin C, Creatine Phosphokinase, Glucose , Na+, K+, Cl ,Ca++, Total CO2, AST, ALT, Total Indirect \& Direct Bilirubin, Alkaline phosphatase, Uric acid, Albumin,Total protein, Fasting lipid Profile Panel; urinalysis(pH, Glucose, Protein, Nitrites, Leukocyte esterase, Microscopy culture);Other(HIV, HBsAg, HBcAb, HepB reflex (HbsAB), if applicable, HCVAb, Serum pregnancy test, Urine pregnancy test, FSH, QFT G or other IGRA, or PPD, EBV, CMV, HSV1, HSV2, VZV, Skin swab for herpetiform rash, Skin swab for potential drug related rash).Retest/discontinuation criteria are defined in Protocol Appendix 6.1 and 6.2 respectively.
Numbers of Participants With Specific Clinical Laboratory Abnormalities During COE Period
时间窗: COE day 1 up to end of study
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology(Hemoglobin, Hematocrit, RBC count, Reticulocyte count, Platelet count, WBC count with differential, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes); serum chemistry (BUN and Creatinine, Cystatin C, Creatine Phosphokinase, Glucose , Na+, K+, Cl ,Ca++, Total CO2, AST, ALT, Total Indirect \& Direct Bilirubin, Alkaline phosphatase, Uric acid, Albumin,Total protein, Fasting lipid Profile Panel; urinalysis(pH, Glucose, Protein, Nitrites, Leukocyte esterase, Microscopy culture);Other(HIV, HBsAg, HBcAb, HepB reflex (HbsAB), if applicable, HCVAb, Serum pregnancy test, Urine pregnancy test, FSH, QFT G or other IGRA, or PPD, EBV, CMV, HSV1, HSV2, VZV, Skin swab for herpetiform rash, Skin swab for potential drug related rash).Retest/discontinuation criteria are defined in Protocol Appendix 6.1 and 6.2 respectively.
次要结局
- Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24 -AT/AU Participants(Baseline, Week 24)
- Percentage of Participants Achieving SALT 30 at Week 24(Baseline, Week 24)
- Change From Baseline in Severity of Alopecia Tool (SALT) Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Percent Change From Baseline in Severity of Alopecia Tool (SALT) Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Percentage of Participants Achieving SALT 30 Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Percentage of Participants Achieving SALT 50 Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Percentage of Participants Achieving SALT 75 Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Percentage of Participants Achieving SALT 90 Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Percentage of Participants Achieving SALT 100 Across Time (Treatment Period)(Baseline, Weeks 2,4,6,8,12,16,20,24)
- Number of Participants With the IGA Score Change (Treatment Period)(baseline, Week 2,4,6,8,12,16,20,24)
- Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Treatment Period(baseline up to Week 24)
- Number of Participants With Laboratory Abnormalities During Treatment Period(Baseline up to Week 24)
- Time to Achieve the Retreatment Criteria During the Withdrawal/Retreatment Part of the Extension Period Among Subjects Who Achieved Primary Endpoint at Week 24 (SBE Period)(Week 24 up to Week 52)
- Change From Baseline in SALT Across Time (SBE Period)(Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment))
- Percentage of Participants Achieving SALT 30 Across Time (SBE Period)(Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment))
- Percentage of Participants Achieving SALT 50 Across Time (SBE Period)(Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment))
- Percentage of Participants Achieving SALT 75 Across Time (SBE Period)(Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment))
- Percentage of Participants Achieving SALT 90 Across Time (SBE Period)(Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment))
- Percentage of Participants Achieving SALT 100 Across Time (SBE Period)(Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment))