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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
71
50 mg tablet, dosed as 200 mg QD or 50 mg QD 50 mg capsule, dosed as 50 mg QD
tablet, dosed as 4 tablets QD or 1 tablet QD
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
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.
Time frame: Baseline, 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 I-V Interwave Latency on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 9
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.
Time frame: Baseline, 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 I-V Interwave Latency on BAEP at 80 dB From the Right Side at Month 6
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.
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Marvel Clinical Research 002, LLC
Huntington Beach, California, United States
University of California, Irvine
Irvine, California, United States
Skin Care Research, LLC
Boca Raton, Florida, United States
Skin Care Research, LLC
Hollywood, Florida, United States
Kendall Adkisson, MD - Intracoastal Dermatology
Jacksonville, Florida, United States
Clinical Neuroscience Solutions, Inc.
Jacksonville, Florida, United States
Y&L Advance Health Care Inc., d/b/a Elite Clinical Research
Miami, Florida, United States
BRCR Medical Center Inc
Miramar, Florida, United States
Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
Orlando, Florida, United States
Orlando Dermatology & Skin Cancer Surgery Center
Oviedo, Florida, United States
...and 28 more locations
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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)
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.
Time frame: Approximately 16 months
Number of Participants Who Discontinued From Study Due to Adverse Event (AEs)
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.
Time frame: Approximately 16 months
Number of Participants Who Discontinued Study Drug Due to AE and Continued Study
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.
Time frame: Approximately 16 months
Number of Participants With Temporary Drug Discontinuation Due to AEs
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.
Time frame: Approximately 16 months
Number of Participants With Clinically Significant Abnormalities in Vital Signs
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.
Time frame: Approximately 16 months
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values
Safety laboratory assessments included the categories of Hematology, Chemistry, Urinalysis and other tests. The clinical significance was determined by the investigator.
Time frame: Approximately 16 months
Change From Baseline in Overall Severity of Alopecia Tool (SALT) Scores up to Month 9
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Months 1, 3, 6 and 9
Number of Participants With PGI-C Response at 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.
Time frame: Month 3E, 6E, 9E, 12E and 15E
Number of Participants With TEAEs and TESAEs: Extension Phase (TP3)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
Safety laboratory assessments included the categories of hematology, chemistry, urinalysis and other tests. The clinical significance was determined by the investigator.
Time frame: From screening up to 28 days after last dose of study treatment (maximum up to 19 months)