A PHASE 2a, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY INVESTIGATING THE SAFETY OF RITLECITINIB (PF-06651600) IN ADULT PARTICIPANTS WITH ALOPECIA AREATA
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 71
- 试验地点
- 37
- 主要终点
- Change From Baseline in I-V Interwave Latency on Brainstem Auditory Evoked Potentials (BAEP) at a Stimulus Intensity of 80 Decibels (dB) From the Right Side at Month 9
研究概览
简要总结
This is a global Phase 2a randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of ritlecitinib in adults aged 18 to ≤50 years of age with ≥25% scalp hair loss due to Alopecia Areata (AA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of alopecia areata, including alopecia totalis and alopecia universalis.
- •At least 25% hair loss due to alopecia areata
- •Must have normal hearing and normal brainstem auditory evoked potentials (BAEPs)
- •Must have a normal neurological exam; can have a stable unilateral median neuropathy or ulnar neuropathy
- •Signed informed consent
- •Stable regimen for other medications before and during the study
排除标准
- •Other significant medical conditions
- •Occupational or recreational noise exposure
- •History of peripheral neuropathy or first degree relative with a hereditary peripheral neuropathy
- •HbA1c > or = 7.5% at Screening
- •Recurrent or disseminated Herpes Zoster
- •Active or chronic infection; or infection requiring hospitalization or IV antimicrobials within 6 months
- •Active or latent (insufficiently treated) Hepatitis
- •Active or latent (insufficiently treated) TB
- •Concomitant medications associated with peripheral neurologic or hearing loss
- •Protocol specific laboratory abnormalities
研究组 & 干预措施
Treatment Arm: PF-06651600
ritlecitinib 200 milligram (mg) once per day (QD) (four 50 mg tablets) for 4 weeks then ritlecitinib 50 mg tablet QD through month 24. At Month 9, participants assigned to this treatment arm will also receive 3 tablets of placebo for 4 weeks to maintain the blind with the other arm. After month 24, participants switch to 50 mg capsules, 1 QD, up to month 60.
干预措施: PF-06651600 (Drug)
Control Arm (Placebo) followed by active therapy extension
matching comparator: placebo QD (4 tablets x 4 weeks then 1 tablet x 8 months) then ritlecitinib 200 mg QD (four 50 mg tablets) for 4 weeks then ritlecitinib 50 mg tablet QD through month 24. After month 24, participants switch to 50 mg capsules, 1 QD, up to month 60.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in I-V Interwave Latency on Brainstem Auditory Evoked Potentials (BAEP) at a Stimulus Intensity of 80 Decibels (dB) From the Right Side at Month 9
时间窗: Baseline, Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
BAEP interwave I-V latency (in milliseconds) was the primary endpoint for this study. High-intensity stimulation (80dB) was used. Participants had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that latency were accurate. Central reading also ensured consistency in BAEP interpretation.
Change From Baseline in I-V Interwave Latency on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 9
时间窗: Baseline, Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
BAEP interwave I-V latency was the primary endpoint for this study. High-intensity stimulation (80dB) was used. Participants had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that latency were accurate. Central reading also ensured consistency in BAEP interpretation.
次要结局
- Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Right Side at Month 6(Baseline, Month 6 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase))
- Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Right Side at Month 9E and 15E(Baseline, Months 9E and 15E (Month 9/15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-controlled Phase.)
- Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Left Side at Month 6(Baseline, Month 6 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase))
- Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Left Side at Month 9E and 15E(Baseline, Month 9E and 15E (Month 9/15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-controlled Phase.)
- Change From Baseline in Percentage of Intraepidermal Nerve Fiber (IENF) With Axonal Swelling in Skin Punch Biopsies at Month 9(Baseline, Month 9 (Month 6 for the 2 participants who entered the Active Therapy Extension Phase at Month 6). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.)
- Change From Baseline in Percentage of IENFs With Axonal Swelling in Skin Punch Biopsies at Month 15E(Baseline, Month 15E (Month 15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.)
- Change From Baseline in Intraepidermal Nerve Fiber Density (IENFD) in Skin Punch Biopsies at Month 9(Baseline, Month 9 (Month 6 for the 2 participants who entered the Active Therapy Extension Phase at Month 6). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.)
- Change From Baseline in IENFD in Skin Punch Biopsies at Month 15E(Baseline, Month 15E (Month 15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.)
- Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Right Side at Month 6 and Month 9(Baseline, Month 6 and Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase))
- Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Right Side at Month 9E and 15E(Baseline, Month 9E and 15E (Month 9 and 15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.)
- Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 6 and Month 9(Baseline, Month 6 and Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase))
- Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 9E and 15E(Baseline, Month 9E and 15E (Month 9 and 15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.)
- Number of Participants With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Right Side up to Month 9(Baseline, Month 6 and 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-Controlled Phase))
- Number of Participants With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Right Side at Baseline, Month 3E, 6E, 9E and 15E(Baseline, Month 3E, 6E, 9E and 15E (Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-Controlled Phase))
- Number of Participants With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Left Side up to Month 9(Baseline, Month 6 and 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-Controlled Phase))
- Number of Participants With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Left Side at Baseline, Month 3E, 6E, 9E and 15E(Baseline, Month 3E, 6E, 9E and 15E (Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-Controlled Phase))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Approximately 16 months)
- Number of Participants Who Discontinued From Study Due to Adverse Event (AEs)(Approximately 16 months)
- Number of Participants Who Discontinued Study Drug Due to AE and Continued Study(Approximately 16 months)
- Number of Participants With Temporary Drug Discontinuation Due to AEs(Approximately 16 months)
- Number of Participants With Clinically Significant Abnormalities in Vital Signs(Approximately 16 months)
- Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values(Approximately 16 months)
- Change From Baseline in Overall Severity of Alopecia Tool (SALT) Scores up to Month 9(Baseline, Months 3, 6 and 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase))
- Change From Baseline in Overall SALT Scores at Month 3E, 6E, 9E, 12E and 15E(Baseline, Month 3E, 6E, 9E, 12E and 15E (Month 3, 6, 9, 12 and 15 in the Active Therapy Extension Phase). Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-Controlled Phase.)
- Change From Baseline in Alopecia Areata - Severity of Alopecia Tool (AA-SALT) Score up to Month 9(Baseline, Months 3, 6 and 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase))
- Change From Baseline in AA-SALT Score at Month 3E, 6E, 9E, 12E and 15E(Baseline, Month 3E, 6E, 9E, 12E and 15E (Baseline was defined as the last non-missing measurement obtained before the first dose in the Placebo-Controlled Phase))
- Number of Participants With Patient's Global Impression of Change (PGI-C) Response up to Month 9(Months 1, 3, 6 and 9)
- Number of Participants With PGI-C Response at 3E, 6E, 9E, 12E and 15E(Month 3E, 6E, 9E, 12E and 15E)
- Number of Participants With TEAEs and TESAEs: Extension Phase (TP3)(From first dose of treatment up to 28 days follow up after last dose of study treatment (Approximately 19 months))
- Number of Participants Who Discontinued From Study Due to AEs: Extension Phase (TP3)(From first dose of treatment up to 28 days follow up after last dose of study treatment (Approximately 19 months))
- Number of Participants With Temporary Drug Discontinuation Due to AEs: Extension Phase (TP3)(From first dose of treatment up to 28 days follow up after last dose of study treatment (Approximately 19 months))
- Number of Participants Who Discontinued Study Drug Due to AE and Continued Study: Extension Phase (TP3)(From first dose of treatment up to 28 days follow up after last dose of study treatment (Approximately 19 months))
- Number of Participants With Clinically Significant Abnormalities in Vital Signs: Extension Phase (TP3)(From screening up to 28 days follow up after last dose of study treatment (maximum up to 19 months))
- Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values: Extension Phase (TP3)(From screening up to 28 days after last dose of study treatment (maximum up to 19 months))