PLACEBO-CONTROLLED SAFETY STUDY OF RITLECITINIB (PF-06651600) IN ADULTS WITH ALOPECIA AREATA

• PF-06651600 (Drug), also known as ritlecitinib: 50 mg tablet, dosed as 200 mg QD or 50 mg QD 50 mg capsule, dosed as 50 mg QD
• Placebo (Drug): tablet, dosed as 4 tablets QD or 1 tablet QD

Primary outcomes

• 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 [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 [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.

Secondary outcomes

• 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)]: 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 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.]: 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 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)]: 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 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.]: 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 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.]: The endpoint "axonal dystrophy" referred to the percentage of IENF with axonal swellings. Axonal swellings were evaluated in peripheral skin punch biopsies from the distal part of lower extremities. Axonal swellings were counted by axon. Any IENF with single or multiple swellings was counted as a single event, ie, a single axon with axonal swellings. For each participant, data were reported as the percentage of IENF with any number of swellings. IENF was assessed at Day 1 and Month 9. Participants who had entered the Active Therapy Extension Phase at Month 6 had a skin punch biopsy taken at Month 6 for IENF assessments instead of at Month 9. The skin biopsy was collected before the start of Active Therapy Extension 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.]: The endpoint "axonal dystrophy" referred to the percentage of IENF with axonal swellings. Axonal swellings were evaluated in peripheral skin punch biopsies from the distal part of lower extremities. Axonal swellings were counted by axon. Any IENF with single or multiple swellings was counted as a single event, ie, a single axon with axonal swellings. For each participant, data were reported as the percentage of IENF with any number of swellings.
• 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.]: IENFD was evaluated in peripheral skin punch biopsies from the distal part of lower extremities. IENFD was measured by counting the number of fibers and fiber branches that independently crossed the dermal-epidermal barrier (basement membrane). Secondary branching was excluded from quantification and fragments were not counted. The length of the histology section was measured (mm) and the linear epidermal nerve fiber density was reported as number of intraepidermal nerve fibers/mm.
• 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.]: IENFD was evaluated in peripheral skin punch biopsies from the distal part of lower extremities. IENFD was measured by counting the number of fibers and fiber branches that independently crossed the dermal-epidermal barrier (basement membrane). Secondary branching was excluded from quantification and fragments were not counted. The length of the histology section was measured (mm) and the linear epidermal nerve fiber density was reported as number of intraepidermal nerve fibers/mm.
• 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)]: 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 amplitude data were accurate. Central reading also ensured consistency in BAEP interpretation.
• 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.]: 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 amplitude data were accurate. Central reading also ensured consistency in BAEP interpretation.
• 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)]: 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 amplitude data were accurate. Central reading also ensured consistency in BAEP interpretation.
• 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.]: 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 amplitude data were accurate. Central reading also ensured consistency in BAEP interpretation.
• 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)]: Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB were summarized descriptively using number of participants by treatment group at each intensity level. At Month 9, 1 participant in 200/50 mg had absence of Wave V on BAEP at a stimulus intensity of 40 dB on the right side. The event was unilateral and showed fluctuations in the presence or absence of Wave V at various intensities on repeat assessments starting at Month 6.
• 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)]: Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB were summarized using number of participants by treatment group at each intensity level. All participants had Wave V on BAEP present at stimulus intensities ranging from 80 dB to 40 dB up to Month 15E except for 1 participant. At Month 9 (TP1), 1 participant in 200/50/50 mg had absence of Wave V on BAEP at a stimulus intensity of 40 dB on the right side. Fluctuations were seen in the presence or absence of Wave V at various intensities on repeat assessments starting at Month 6 on the right side.
• 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)]: Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB were summarized descriptively using number of participants by treatment group at each intensity level.
• 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)]: Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB were summarized descriptively using number of participants by treatment group at each intensity level. All participants had Wave V on BAEP present at stimulus intensities ranging from 80 dB to 40 dB up to Month 15E except for 1 participant. At Month 9 (TP1), 1 participant in 200/50/50 mg had absence of Wave V on BAEP at a stimulus intensity of 40 dB on the right side. Fluctuations were seen in the presence or absence of Wave V at various intensities on repeat assessments starting at Month 6 on the right side.
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [Approximately 16 months]: An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Seriousness of an AE was assessed under the criteria of serious adverse event (SAE). An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. Relatedness to study treatment was determined by the investigator.
• Number of Participants Who Discontinued From Study Due to Adverse Event (AEs) [Approximately 16 months]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Participants who had an AE record that indicated that the AE caused the participant to be discontinued from the study. Relatedness to study treatment was determined by the investigator.
• Number of Participants Who Discontinued Study Drug Due to AE and Continued Study [Approximately 16 months]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. This Outcome Measures presented the number of participants who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Relatedness to study treatment was determined by the investigator.
• Number of Participants With Temporary Drug Discontinuation Due to AEs [Approximately 16 months]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with temporary drug discontinuation due to both all-causality and treatment-related AEs are presented below. Relatedness to study treatment was determined by the investigator.
• Number of Participants With Clinically Significant Abnormalities in Vital Signs [Approximately 16 months]: Oral, tympanic, or axillary temperature, pulse rate, respiratory rate, and blood pressure (BP) were assessed. BP and pulse measurements were assessed in a chair, back supported and arms bared (free of restrictions such as rolled-up sleeves, etc) and supported at heart level. Measurements were taken on the same arm at each visit (preferably non-dominant) with a completely automated device. Pulse rate was measured at approximately the same time as BP for a minimum of 30 seconds. BP and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones). Participants refrained from smoking or ingesting caffeine during the 30 minutes preceding the measurements. The clinical significance was determined by the investigator.
• Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values [Approximately 16 months]: Safety laboratory assessments included the categories of Hematology, Chemistry, Urinalysis and other tests. The clinical significance was determined by the investigator.
• 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)]: SALT is a quantitative assessment of AA severity based on scalp terminal hair loss. The overall SALT score included hair loss regardless of etiology (ie, scalp hair loss due to both non-AA and AA) and was collected at study visits. The Overall SALT Score ranged from 0 to 100%, with higher scores representing greater amount of hair loss.
• 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.]: SALT is a quantitative assessment of AA severity based on scalp terminal hair loss. The overall SALT score included hair loss regardless of etiology (ie, scalp hair loss due to both non-AA and AA) and was collected at study visits. The Overall SALT Score ranged from 0 to 100%, with higher scores representing greater amount of hair loss.
• 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)]: SALT is a quantitative assessment of AA severity based on scalp terminal hair loss. AA-SALT is the amount of scalp hair loss due to AA. AA SALT score in Placebo-Controlled Phase = overall SALT score - non-AA SALT score (The non-AA SALT score only took into account scalp hair loss other than that due to AA and was required to be assessed only at Month 9 \[or Month 6 for those who entered the Active Therapy Extension Phase at Month 6\] in Placebo-Controlled Phase). The AA-SALT Score ranged from 0 to 100%, with higher scores representing greater amount of hair loss.
• 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)]: SALT is a quantitative assessment of AA severity based on scalp terminal hair loss. AA-SALT is the amount of scalp hair loss due to AA. AA SALT score = overall SALT score - non-AA SALT score (The non-AA SALT score only took into account scalp hair loss other than that due to AA and was required to be assessed only at Month 9 \[or Month 6 for those who entered the Active Therapy Extension Phase at Month 6\] in Placebo-Controlled Phase). The AA-SALT Score ranged from 0 to 100%, with higher scores representing greater amount of hair loss.
• Number of Participants With Patient's Global Impression of Change (PGI-C) Response up to Month 9 [Months 1, 3, 6 and 9]: The PGI-C asked the participants to evaluate the improvement or worsening of their AA as compared to the start of the study using a single item, "Since the start of the study, my alopecia areata has: …". The participants selected one of seven responses ranging from "greatly improved" to "greatly worsened". This Outcome Measure presented the number of participants with PGI-C response which was defined as "greatly improved" or "moderately improved". Participants with missing PGI-C scores were considered as non-responders.
• Number of Participants With PGI-C Response at 3E, 6E, 9E, 12E and 15E [Month 3E, 6E, 9E, 12E and 15E]: The PGI-C asked the participants to evaluate the improvement or worsening of their AA as compared to the start of the study using a single item, "Since the start of the study, my alopecia areata has: …". The participants selected one of seven responses ranging from "greatly improved" to "greatly worsened". This Outcome Measure presented the number of participants with PGI-C response which was defined as "greatly improved" or "moderately improved". Participants with missing PGI-C scores were considered as non-responders.
• 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)]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Seriousness of an AE was assessed under the criteria of SAE. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. Relatedness to study treatment was determined by the investigator.
• 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)]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Participants who had an AE record that indicated that the AE caused the participant to be discontinued from the study. Relatedness to study treatment was determined by the investigator.
• 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)]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. This outcome measure presented the number of participants who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Relatedness to study treatment was determined by the investigator.
• 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)]: An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with temporary drug discontinuation due to both all-causality and treatment-related AEs are presented below. Relatedness to study treatment was determined by the investigator.
• 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)]: Oral, tympanic, or axillary temperature, pulse rate, respiratory rate, and blood pressure (BP) were assessed. BP and pulse measurements were assessed in a chair, back supported and arms bared (free of restrictions such as rolled-up sleeves, etc) and supported at heart level. Measurements were taken on the same arm at each visit (preferably non-dominant) with a completely automated device. Pulse rate was measured at approximately the same time as BP for a minimum of 30 seconds. BP and pulse measurements preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones). Participants were refrained from smoking or ingesting caffeine during the 30 minutes preceding the measurements. The clinical significance was determined by the investigator.
• 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)]: Safety laboratory assessments included the categories of hematology, chemistry, urinalysis and other tests. The clinical significance was determined by the investigator.

Sex: All, ages: 18 Years to 50 Years

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Participant flow

Outcome results

• 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 (Primary), Least squares mean, Millisecond (ms): Ritlecitinib 200/50 mg QD 0.011 (-0.043 to 0.065); Placebo -0.010 (-0.063 to 0.043)
• Change From Baseline in I-V Interwave Latency on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 9 (Primary), Least squares mean, ms: Ritlecitinib 200/50 mg QD 0.031 (-0.012 to 0.075); Placebo 0.022 (-0.020 to 0.065)
• Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Right Side at Month 6 (Secondary), Least squares mean, millisecond (ms): Ritlecitinib 200/50 mg QD -0.030 (-0.072 to 0.011); Placebo -0.024 (-0.065 to 0.017)
• Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Right Side at Month 9E and 15E (Secondary), Mean, millisecond (ms): Ritlecitinib 200/50/50 mg QD 0.010 +/- 0.1233; Placebo -> Ritlecitinib 200/50 mg QD -0.033 +/- 0.2448
• Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Left Side at Month 6 (Secondary), Least squares mean, millisecond (ms): Ritlecitinib 200/50 mg QD 0.021 (-0.011 to 0.054); Placebo -0.020 (-0.053 to 0.012)
• Change From Baseline in I-V Interwave Latency on BAEP at 80 dB From the Left Side at Month 9E and 15E (Secondary), Mean, millisecond (ms): Ritlecitinib 200/50/50 mg QD 0.006 +/- 0.1109; Placebo -> Ritlecitinib 200/50 mg QD 0.056 +/- 0.1694
• Change From Baseline in Percentage of Intraepidermal Nerve Fiber (IENF) With Axonal Swelling in Skin Punch Biopsies at Month 9 (Secondary), Median, Percentage of Nerve Fibers: Ritlecitinib 200/50 mg QD 0.0 (-0.5 to 2.5); Placebo 0.0 (-2.0 to 1.0)
• Change From Baseline in Percentage of IENFs With Axonal Swelling in Skin Punch Biopsies at Month 15E (Secondary), Median, Percentage of Nerve Fibers: Ritlecitinib 200/50/50 mg QD 0 (-1.0 to 0); Placebo -> Ritlecitinib 200/50 mg QD 0 (-1.0 to 0)
• Change From Baseline in Intraepidermal Nerve Fiber Density (IENFD) in Skin Punch Biopsies at Month 9 (Secondary), Mean, fibers/mm: Ritlecitinib 200/50 mg QD -0.4 +/- 3.90; Placebo -0.2 +/- 2.72
• Change From Baseline in IENFD in Skin Punch Biopsies at Month 15E (Secondary), Mean, fibers/mm: Ritlecitinib 200/50/50 mg QD 0.2 +/- 2.85; Placebo -> Ritlecitinib 200/50 mg QD -1.1 +/- 3.51
• 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 (Secondary), Least squares mean, Microvolts (μV): Ritlecitinib 200/50 mg QD -0.031 (-0.063 to 0); Placebo -0.017 (-0.048 to 0.015)
• 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 (Secondary), Mean, μV: Ritlecitinib 200/50/50 mg QD -0.052 +/- 0.1109; Placebo -> Ritlecitinib 200/50 mg QD -0.025 +/- 0.1649
• 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 (Secondary), Least squares mean, μV: Ritlecitinib 200/50 mg QD -0.047 (-0.082 to -0.013); Placebo -0.019 (-0.053 to 0.015)
• 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 (Secondary), Mean, μV: Ritlecitinib 200/50/50 mg QD -0.058 +/- 0.1209; Placebo -> Ritlecitinib 200/50 mg QD -0.025 +/- 0.1307
• 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 (Secondary), Count of participants, Participants: Ritlecitinib 200/50 mg QD 0; Placebo 0
• 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 (Secondary), Count of participants, Participants: Ritlecitinib 200/50/50 mg QD 0; Placebo -> Ritlecitinib 200/50 mg QD 0
• 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 (Secondary), Count of participants, Participants: Ritlecitinib 200/50 mg QD 0; Placebo 0
• 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 (Secondary), Count of participants, Participants: Ritlecitinib 200/50/50 mg QD 0; Placebo -> Ritlecitinib 200/50 mg QD 0
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) (Secondary), Count of participants, Participants: Ritlecitinib 200/50 mg QD - Placebo-Controlled Phase 29; Placebo - Placebo-Controlled Phase 22; Ritlecitinib 50 mg QD - Active Therapy Extension Phase 3; Ritlecitinib 200/50 mg QD - Active Therapy Extension Phase 3
• Number of Participants Who Discontinued From Study Due to Adverse Event (AEs) (Secondary), Count of participants, Participants: Ritlecitinib 200/50 mg QD - Placebo-Controlled Phase 0; Placebo - Placebo-Controlled Phase 0; Ritlecitinib 50 mg QD - Active Therapy Extension Phase 1; Ritlecitinib 200/50 mg QD - Active Therapy Extension Phase 0
• 16 more outcome measures not shown.

Adverse events

Time frame: Placebo controlled phase (TP1) & Active therapy extension phase (TP2): 24 months, Extension phase (TP3): From first dose of treatment up to 28 days follow up after last dose of study treatment (Approximately 19 months)

Serious adverse events by term

Other adverse events by term

• Results publication: Senna M, Hanna S, Ueki R, Zhang X, Aguh C, Piraccini BM, Wajsbrot D, Nagy E, Sadrarhami M, Chen S, Wolk R, Tran H, Lejeune A. Updated Integrated Safety Analysis of Ritlecitinib up to ~ 5 Years in Patients with Alopecia Areata from the ALLEGRO Clinical Trial Program. Am J Clin Dermatol. 2026 Jul 22. doi: 10.1007/s40257-026-01062-x. Online ahead of print. PMID 42481842
• Results publication: Senna M, Soung J, Figueras I, King B, Kinoshita-Ise M, Hanna S, Wu W, Wajsbrot D, Woodworth D, Wolk R, Chaudhry A, Lejeune A, Tran H. Long-Term Efficacy and Safety of Ritlecitinib in Adults and Adolescents with Alopecia Areata: 3-Year Results from the ALLEGRO Phase 2b/3 and ALLEGRO-LT Phase 3 Clinical Studies. Am J Clin Dermatol. 2026 Mar 31. doi: 10.1007/s40257-026-01029-y. Online ahead of print. PMID 41917311
• Results publication: King B, Soung J, Tziotzios C, Rudnicka L, Joly P, Gooderham M, Sinclair R, Mesinkovska NA, Paul C, Gong Y, Anway SD, Tran H, Wolk R, Zwillich SH, Lejeune A. Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program. Am J Clin Dermatol. 2024 Mar;25(2):299-314. doi: 10.1007/s40257-024-00846-3. Epub 2024 Jan 23. PMID 38263353

• Study Protocol (PDF, 2022-04-28)
• Statistical Analysis Plan (PDF, 2023-04-04)

• Pfizer CT.gov Call Center, Study director, Pfizer