A PHASE 3 OPEN-LABEL, MULTI-CENTER, LONG-TERM STUDY INVESTIGATING THE SAFETY AND EFFICACY OF PF-06651600 IN ADULT AND ADOLESCENT PARTICIPANTS WITH ALOPECIA AREATA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 1,057
- 试验地点
- 255
- 主要终点
- Main Study: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Until Follow-up Visit
研究概览
简要总结
This is a global Phase 3 study to evaluate the safety and effectiveness of an investigational study drug (called PF-06651600) in adults and adolescents (12 years and older) who have alopecia areata. Eligible patients from the prior studies B7931005 (NCT02974868) and B7981015 (NCT03732807) will have an opportunity to enroll as well as patients who have not previously participated in either of these studies. The study is open-label and all patients entering the study will receive active study drug.
A sub-study of approximately 60 adult patients who are participating in the B7981032 study will be conducted at select sites in the US, Australia and Canada. The sub-study will evaluate the immune response to tetanus and meningococcal vaccines in patients who have received a minimum of 6 months of 50 mg PF-06651600.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For de novo participants and participants from Study B7931005 and B7981015 with >30 days between first visit in B7981032 and last dose in the prior study:
- •Clinical diagnosis of alopecia areata (AA) with no other cause of hair loss. Androgenetic alopecia coexistent with AA is allowed.
- •De novo participants >=12 to <18 years of age: >=50% terminal hair loss of the scalp due to AA, including alopecia totalis and alopecia universalis
- •De novo participants >=18 years of age and participants from Study B7931005 or B7981015 with >30 days between first visit in B7981032 and last dose in the prior study: >=25% terminal hair loss of the scalp due to AA, including alopecia totalis and alopecia universalis
- •No evidence of terminal scalp hair regrowth within 6 months (de novo only)
- •Current episode of terminal scalp hair loss <=10 years (de novo only)
排除标准
- •For de novo participants and participants from Study B7931005 and B7981015 with >30 days between first visit in B7981032 and last dose in the prior study:
- •Hearing loss with progression over previous 5 years, or sudden hearing loss, or middle or inner ear disease, or other auditory condition that is considered acute, fluctuating or progressive
- •History of or current malignancies with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ
- •History of a single episode of disseminated herpes zoster or disseminated herpes simplex, or a history of more than one episode of localized, dermatomal herpes zoster
- •Infection requiring hospitalization, or parenteral antimicrobial therapy within 6 months prior to Day 1
- •Exclusion criteria for all participants:
- •- Participants who have previously taken Janus kinase (JAK) inhibitors other than PF-06651600 must have received the last dose >12 weeks prior to the screening visit
研究组 & 干预措施
Treatment sequence 1
Participants who did not previously receive study intervention in either study B7931005 or B7981015 will receive 200 milligrams (mg) PF-06651600, given as four 50 mg tablets once daily (QD) for 1 month, followed by 50 mg PF-06651600 tablet or capsule given QD for 59 months.
Patients participating in the vaccine sub-study will receive the 2 vaccines or one of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 9 visit and prior to or on the Month 56 visit of the main B7981032 study.
干预措施: PF-06651600 (Drug)
Treatment sequence 2
Participants who previously received study intervention in either study B7931005 or B7981015 will receive 50 mg PF-06651600 tablet or capsule given QD for 59 months.
Patients participating in the vaccine sub-study will receive the 2 vaccines or 1 of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 6 visit and prior to or on the Month 56 visit of the main B7981032 study.
干预措施: PF-06651600 (Drug)
Treatment sequence 1
Participants who did not previously receive study intervention in either study B7931005 or B7981015 will receive 200 milligrams (mg) PF-06651600, given as four 50 mg tablets once daily (QD) for 1 month, followed by 50 mg PF-06651600 tablet or capsule given QD for 59 months.
Patients participating in the vaccine sub-study will receive the 2 vaccines or one of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 9 visit and prior to or on the Month 56 visit of the main B7981032 study.
干预措施: Meningococcal (groups A, C, W-135 and Y [ACWY]) oligosaccharide diphtheria CRM197 conjugate vaccine (Biological)
Treatment sequence 1
Participants who did not previously receive study intervention in either study B7931005 or B7981015 will receive 200 milligrams (mg) PF-06651600, given as four 50 mg tablets once daily (QD) for 1 month, followed by 50 mg PF-06651600 tablet or capsule given QD for 59 months.
Patients participating in the vaccine sub-study will receive the 2 vaccines or one of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 9 visit and prior to or on the Month 56 visit of the main B7981032 study.
干预措施: Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine (Biological)
Treatment sequence 2
Participants who previously received study intervention in either study B7931005 or B7981015 will receive 50 mg PF-06651600 tablet or capsule given QD for 59 months.
Patients participating in the vaccine sub-study will receive the 2 vaccines or 1 of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 6 visit and prior to or on the Month 56 visit of the main B7981032 study.
干预措施: Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine (Biological)
Treatment sequence 2
Participants who previously received study intervention in either study B7931005 or B7981015 will receive 50 mg PF-06651600 tablet or capsule given QD for 59 months.
Patients participating in the vaccine sub-study will receive the 2 vaccines or 1 of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 6 visit and prior to or on the Month 56 visit of the main B7981032 study.
干预措施: Meningococcal (groups A, C, W-135 and Y [ACWY]) oligosaccharide diphtheria CRM197 conjugate vaccine (Biological)
结局指标
主要结局
Main Study: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Until Follow-up Visit
时间窗: From start of study intervention (Day 1) until follow-up visit (4 weeks after last dose in Treatment period 1) (Up to Month 40)
An AE is 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 was considered treatment emergent if the event had start date on or after the first dosing date of this study.
Main Study: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation Until Follow-up Visit
时间窗: From start of study intervention (Day 1) until follow-up visit (4 weeks after last dose in Treatment period 1) (Up to Month 40)
An AE is 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 SAE was any untoward medical occurrence that at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; other important medical events. AEs leading to discontinuation included participants who had an AE record that indicated that the AE caused the participant to be discontinued from the study or that action taken with study treatment was drug withdrawn.
Main Study: Number of Participants According to Categorization of Vital Signs Data Until Follow-up Visit
时间窗: From start of study intervention (Day 1) until follow-up visit (4 weeks after last dose in Treatment period 1) (Up to Month 40)
Vital signs including blood pressure included systolic blood pressure (SBP) \[Millimeters of mercury, mmHg\]) and diastolic blood pressure (DBP) and pulse rate \[beats per minute (bpm)\] were measured using an automated device in a sitting position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Criteria for vital sign abnormalities included: SBP\<90mmHg, DBP\<50 mmHg and pulse rate\<40mmHg.
Main Study: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values Until Follow-up Visit
时间窗: From start of study intervention (Day 1) until follow-up visit (4 weeks after last dose in Treatment period 1) (Up to Month 40)
Criteria for laboratory abnormalities included:Hemoglobin, Hematocrit, Erythrocytes (\<0.8\*LLN); Ery. Volume, Hemoglobin,Mean Corpuscular HGB Concentration \<0.8\*LLN or \>1.5\*LLN;Reticulocytes, Leukocytes, Lymphocytes, Neutrophils, Neutrophils, Basophils, Eosinophils, Monocytes (\>1.2\*ULN), Prothrombin Time(\>1.1\*ULN).Clinical Chemistry: Bilirubin, Direct Bilirubin, Indirect Bilirubin (1.5\*ULN), Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase, Alkaline Phosphatase (\>3.0\*ULN); Albumin, Urate (\<0.8\*LLN and \>1.2\*ULN; Urea Nitrogen,Creatinine Cholesterol \>1.3\*ULN; Cholesterol \<0.8\*LLN or \>1.2\*LLN, Triglycerides,Potassium,Calcium \< 0.9x LLN \& \> 1.1x ULN; Bicarbonate, Glucose, Creatine Kinase. Urinalysis: Glucose, Ketones, Protein, Hemoglobin, Urobilinogen, Bilirubin, Nitrite \>=1; Leukocyte Erythrocytes, Leukocytes \>=20; Epithelial Cells\>=6, Hyaline Cast\>1; Bacteria\>20. Number of participants with any laboratory abnormality meeting specified criteria is included.
Vaccine Sub-study: Percentage of Participants With Tetanus Booster Response
时间窗: Month 1
Booster response to tetanus toxoid was defined as: \>=4-fold rise in anti-tetanus toxoid immunoglobulin G (IgG) antibody concentration at Month 1 if the pre-vaccination concentration was \<=2.7 International Units per milliliter (IU/mL); OR \>=2-fold rise in anti-tetanus toxoid IgG antibody concentration if the pre-vaccination concentration was \>2.7 IU/mL. Two-sided 95% confidence interval (CI) was based on Clopper-Pearson exact method.
次要结局
- Main Study: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Until End of Study(From start of study intervention (Day 1) until end of study)
- Main Study: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation Until End of Study(From start of study intervention (Day 1) until end of study)
- Main Study: Number of Participants With Clinically Significant Abnormalities in Vital Signs Until End of Study(From start of study intervention (Day 1) until end of study)
- Main Study: Number of Participants With Clinically Significant Laboratory Abnormalities Until End of Study(From start of study intervention (Day 1) until end of study)
- Main Study: Percentage of Participants Achieving Response Based on Severity of Alopecia Tool (SALT) Overall Score <=10 at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Percentage of Participants Achieving Response Based on Alopecia Areata (AA) SALT Score <=10 at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Percentage of Participants Achieving Response Based on SALT Overall Score <= 20 at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Percentage of Participants Achieving Response Based on AA SALT Score <=20 at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Change From Baseline in SALT Overall Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(Baseline, At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Change From Baseline in AA SALT Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(Baseline, At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Percentage of Participants Achieving Atleast 75% Improvement in Overall SALT Score From Baseline at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Percentage of Participants Achieving Atleast 75% Improvement in AA SALT Score From Baseline at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36(At Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32 and 36)
- Main Study: Percentage of Participants Achieving Atleast 2-Grade Improvement From Baseline or Absolute Score of 3 in the Eyebrow Assessment (EBA) at Months 1, 3, 6, 12, 18, 24 and 36 in Participants Without Normal EBA Score at Baseline(At Months 1, 3, 6, 12, 18, 24 and 36)
- Main Study: Percentage of Participants Achieving Atleast 2-Grade Improvement From Baseline or Absolute Score of 3 in the Eyelash Assessment (ELA) at Months 1, 3, 6, 12, 18, 24 and 36 in Participants Without Normal ELA Score at Baseline(At Months 1, 3, 6, 12, 18, 24 and 36)
- Main Study: Percentage of Participants Achieving Patient's Global Impression of Change (PGI-C) Score of Moderately Improved or Greatly Improved at Months 1, 3, 6, 9, 12, 18, 24 and 36(At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Main Study: Change From Baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) Domain Scores at Months 1, 3, 6, 9, 12, 18, 24 and 36: Emotional Symptoms and Activity Limitations(Baseline, At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Main Study: Percentage of Participants With Response Based on Hair Loss Improvement From Baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) Domain Scores at Months 1, 3, 6, 9, 12, 18, 24 and 36, Among Participants With Score >=2 at Baseline(Baseline, At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Main Study: Change From Baseline in Depression Subscale Score of Hospital Anxiety and Depression Scale (HADS) at Months 1, 3, 6, 9, 12, 18, 24 and 36(Baseline, At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Main Study: Change From Baseline in Anxiety Subscale Score of Hospital Anxiety and Depression Scale (HADS) at Months 1, 3, 6, 9, 12, 18, 24 and 36(Baseline, At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Main Study: Percentage of Participants With Improvement on HADS Depression Score at Months 1, 3, 6, 9, 12, 18, 24 and 36(At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Main Study: Percentage of Participants With Improvement on HADS Anxiety Score At Months 1, 3, 6, 9, 12, 18, 24 and 36(At Months 1, 3, 6, 9, 12, 18, 24 and 36)
- Vaccine Sub-study: Percentage of Participants With Anti-tetanus Antibody Level >=1.0 International Units Per Milliliter (IU/mL) at Month 1-Tdap Vaccination(Month 1)
- Vaccine Sub-study: Percentage of Participants With Anti-tetanus Antibody Level >=0.1 IU/mL at Month 1-Tdap Vaccination(Month 1)
- Vaccine Sub-study: Percentage of Participants With >=4 Times Increase in Anti-tetanus Antibody Level From Baseline at Month 1-Tdap Vaccination(Month 1)
- Vaccine Sub-study: Geometric Mean Fold Change in Anti-tetanus Levels Above Baseline Values at Month 1-Tdap Vaccination(From Baseline (pre-vaccination on Day 1) to Month 1)
- Vaccine Sub-study: Geometric Mean Concentrations (GMCs) of Anti-tetanus Antibody Levels at Month 1-Tdap Vaccination(Month 1)
- Vaccine Sub-study: Percentage of Participants With Human Serum Bactericidal Activity (hSBA) Titer >=1:8 at Month 1 Post-vaccination for Serogroup C-Meningococcal ACWY Vaccination(Month 1)
- Vaccine Sub-study: Percentage of Participants With hSBA Titer >=1:4 at Month 1 Post-vaccination for Serogroup C-Meningococcal ACWY Vaccination(Month 1)
- Vaccine Sub-study: Geometric Mean Titers (GMT) of Antibodies for Serogroup C at Baseline and Month 1-Meningococcal ACWY Vaccination(Baseline (pre-vaccination on Day 1) and Month 1)
- Vaccine Sub-study: Number of Participants With SAEs(From day of vaccination (Day 1) up to 35 days post last dose of vaccine (up to Day 36))
- Vaccine Sub-study: Number of Participants With AEs(From day of vaccination (Day 1) up to 35 days post last dose of vaccine (up to Day 36))
- Vaccine Sub-study: Number of Participants With AEs Leading to Discontinuation(From day of vaccination (Day 1) up to 35 days post last dose of vaccine (up to Day 36))