Study to Evaluate the Efficacy and Safety of CTP-543 in Adults With Moderate to Severe Alopecia Areata (THRIVE-AA1)

Study Overview
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Brief Summary
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This study evaluates the safety and effectiveness of an investigational study drug (called CTP-543) in adults (18 years and older) who have 50% or greater scalp hair loss.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of CTP-543 in Adult Patients With Moderate to Severe Alopecia Areata (THRIVE-AA1)

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: CTP-543 matching placebo
* Drug: CTP-543
* Drug: CTP-543


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical presentation compatible with alopecia areata with a current episode lasting at least 6 months and not exceeding 10 years at the time of Screening. Total disease duration greater than 10 years is permitted. At least 50% scalp hair loss, as defined by a Severity of Alopecia Tool (SALT) score ≥50, at Screening and Baseline. Willing to comply with the study visits and requirements of the study protocol. Exclusion Criteria: Treatment with other medications or agents within 1 month of Baseline or during the study that may affect hair regrowth or immune response. Active scalp inflammation, psoriasis, or seborrheic dermatitis requiring topical treatment to the scalp, significant trauma to the scalp, or other scalp condition that may interfere with the SALT assessment, or untreated actinic keratosis anywhere on the body at Screening and/or Baseline. Treatment with systemic immunosuppressive medications within 3 months of Screening or during the study, or biologics within 6 months of Screening or during the study. Females who are nursing, pregnant, or planning to become pregnant while in the study, and for 30 days after last dose of study drug. Clinically significant medical condition, psychiatric disease, or social condition, as determined by the Investigator, that may unfavorably alter the risk-benefit of study participation, adversely affect study compliance, or confound interpretation of study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br>Participants received CTP-543 matched placebo tablets, orally, twice daily (BID) for up to 24 weeks. | Drug: CTP-543 matching placebo<br>* Administered as tablets.<br>|
| Experimental: CTP-543 8 mg BID<br>Participants received CTP-543 8 mg tablets, orally, BID for up to 24 weeks. | Drug: CTP-543<br>* Administered as tablets.<br>|
| Placebo Comparator: CTP-543 12 mg BID<br>Participants received CTP-543 12 mg tablets, orally, BID for up to 24 weeks. | Drug: CTP-543<br>* Administered as tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Absolute Severity of Alopecia Tool (SALT) Score of ≤20 at Week 24 | SALT is a quantitative assessment of scalp hair loss with scores ranging in severity from 0 (no scalp hair loss) to a maximum of 100 (complete scalp hair loss). | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders on the Hair Satisfaction Patient Reported Outcome (SPRO) Scale at Weeks 12, 16, 20, and 24 | SPRO is a questionnaire answered by the participant and designed to measure how satisfied alopecia areata participants are with their hair at the time of the assessment. The responses range from 1 to 5: 1= very satisfied, 2= satisfied, 3= neither satisfied nor dissatisfied, 4= dissatisfied, and 5= very dissatisfied. Responders were defined as participants with responses of satisfied or very satisfied. | Weeks 12, 16, 20, and 24 | 
| Percentage of Participants Achieving an Absolute SALT Score of ≤20 at Weeks 4, 8, 12, 16, and 20 | SALT is a quantitative assessment of scalp hair loss with scores ranging in severity from 0 (no scalp hair loss) to a maximum of 100 (complete scalp hair loss). | Weeks 4, 8, 12, 16, and 20 | 
| Relative Change in SALT Scores From Baseline at Weeks 4, 8, 12, 16, 20, and 24 | SALT is a quantitative assessment of scalp hair loss with scores ranging in severity from 0 (no scalp hair loss) to a maximum of 100 (complete scalp hair loss). Relative change (percent change) to baseline is calculated as: 100 x ([post-baseline SALT score - baseline SALT score]/baseline SALT score). | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Responders Assessed Using the Clinician Global Impression of Improvement (CGI-I) at Weeks 12, 16, 20, and 24 | The CGI-I is a questionnaire that asks the clinician to evaluate the improvement or worsening of the participant's alopecia areata as compared to the start of the study on a 7-point scale. Responses range from 1 (very much worse) to 7 (very much improved). Responders were defined as participants with responses of 6 (much improved) or 7 (very much improved). | Weeks 12, 16, 20, and 24 | 
| Percentage of Responders Assessed Using the Patient Global Impression of Improvement (PGI-I) at Weeks 12, 16, 20, and 24 | The PGI-I is a self-administered questionnaire that asks the participant to evaluate the improvement or worsening of their alopecia areata as compared to the start of the study on a 7-point scale. Responses range from 1 (very much worse) to 7 (very much improved). Responders were defined as participants with responses of 6 (much improved) or 7 (very much improved). | Weeks 12, 16, 20, and 24 | 
| Change in the Clinician Global Impression of Severity (CGI-S) Scores From Baseline at Weeks 12, 16, 20, and 24 | The CGI-S is a questionnaire that asks the clinician to evaluate the symptom severity of the participant's alopecia areata at the time of assessment. The symptom severity was rated on a scale ranging from 1 to 7, where 1=normal, no hair loss; 2=borderline hair loss; 3=mild hair loss; 4=moderate hair loss; 5=marked hair loss; 6=severe hair loss; 7=among the most extreme hair loss. Higher scores indicate more hair loss. A negative change from baseline indicates less hair loss. | Baseline, Weeks 12, 16, 20, and 24 | 
| Change in the Patient Global Impression of Severity (PGI-S) Scores From Baseline at Weeks 12, 16, 20, and 24 | The PGI-S is a self-administered questionnaire that asks the participant to evaluate the symptom severity of their alopecia areata at the time of assessment. Symptom severity was rated on a scale ranging from 1 to 7, where 1=normal, no hair loss; 2=borderline hair loss; 3=mild hair loss; 4=moderate hair loss; 5=marked hair loss; 6=severe hair loss; 7=among the most extreme hair loss. Higher scores indicate more hair loss. A negative change from baseline indicates less hair loss. | Baseline, Weeks 12, 16, 20, and 24 | 
| Percentage of Participants Achieving at Least a 75% and 90% Relative Reduction in SALT Score From Baseline at Weeks 12 and 24 | SALT is a quantitative assessment of scalp hair loss with scores ranging in severity from 0 (no scalp hair loss) to a maximum of 100 (complete scalp hair loss). Percentage of participants achieving at least a 75% and 90% relative reduction in SALT score from baseline at Weeks 12 and 24 are reported. | Baseline, Weeks 12, and 24 | 
| Change in the Brigham Eyebrow Tool for Alopecia (BETA) Scores From Baseline at Weeks 12 and 24 | BETA is a clinician-rated scale that assesses the total eyebrow hair present. The BETA score is calculated based on hair density and surface area of each individual eyebrow of the participant, ranging from 0 to 3, where 0 = no eyebrow, 1 = minimal eyebrow, 2 = moderate eyebrow, 3 = normal eyebrow. The BETA score is the sum of the right and left eyebrow scores, ranging from 0 to 6. Higher scores indicate less hair loss of eyebrows. A positive change from baseline indicates less hair loss of eyebrows. | Baseline, Weeks 12, and 24 | 
| Change in the Brigham Eyelash Tool for Alopecia (BELA) Scores From Baseline at Weeks 12 and 24 | BELA is a clinician-rated scale that assesses the total eyelash hair present. The BELA is calculated based on distribution and grade values, ranging from 0 (no eyelashes) to 3 (full eyelashes). The BELA score is the sum of the individual scores for the left and right eyes, ranging from 0 to 6. Higher scores indicate less hair loss of eyelashes. A positive change from baseline indicates less hair loss of eyelashes. | Baseline, Weeks 12, and 24 | 
| Change in the SPRO Scale From Baseline at Weeks 12, 16, 20, and 24 | SPRO is a questionnaire answered by the participant and designed to measure how satisfied alopecia areata participants are with their hair at the time of the assessment. The responses range from 1 to 5: 1= very satisfied, 2= satisfied, 3= neither satisfied nor dissatisfied, 4= dissatisfied, and 5= very dissatisfied. Higher scores indicate the greater hair dissatisfaction. A negative change from baseline indicate the greater hair satisfaction. | Baseline, Weeks 12, 16, 20, and 24 | 
| Percentage of Participants Achieving a ≥2-point Change From Baseline in the SPRO Scale at Weeks 12, 16, 20, and 24 | SPRO is a questionnaire answered by the participant and designed to measure how satisfied alopecia areata participants are with their hair at the time of the assessment. The responses range from 1 to 5: 1= very satisfied, 2= satisfied, 3= neither satisfied nor dissatisfied, 4= dissatisfied, and 5= very dissatisfied. | Weeks 12, 16, 20, and 24 | 
| Change in the Individual Items of the Hair Quality Patient Reported Outcome (QPRO) Scale From Baseline at Weeks 12, 16, 20, and 24 | The QPRO questionnaire provides additional details on key attributes of hair and helps provide context to the SPRO response. The individual items of QPRO are: Satisfied thickness hair coverage; Satisfied evenness hair coverage; How satisfied with your eyebrows; How satisfied with your eyelashes, scored on a scale ranging from 1 to 5 where 1=very satisfied, 2=satisfied, 3=neither satisfied nor dissatisfied, 4=dissatisfied, 5=very dissatisfied. Higher scores indicate the greater dissatisfaction on hair quality. A negative change from baseline indicate the greater satisfaction on hair quality. | Baseline, Weeks 12, 16, 20, and 24 | 
| Change in the Anxiety and Depression Scale Scores of the Hospital Anxiety and Depression Scale (HADS) From Baseline at Week 24 | HADS is a questionnaire designed to assess anxiety and depression symptoms which is completed by participants. The questionnaire is comprised of two separate scales with a total of 14 items: A 7-item scale related to anxiety and 7-item scale related to depression. Each item within both scales is scored using a 4-point scale, ranging from 0 to 3 and the total scores in each scale can range from 0 to 21. Separate scores were created for anxiety and depression. A score between 0-7 is considered normal, 8-10 is mild, 11-14 is moderate, and >14 is severe anxiety or depression. Higher scores indicate greater severity. A negative change from baseline indicates less severity. | Baseline and Week 24 | 
| Percentage of Participants Achieving an Absolute SALT Score of ≤10 at Week 24 | SALT is a quantitative assessment of scalp hair loss with scores ranging in severity from 0 (no scalp hair loss) to a maximum of 100 (complete scalp hair loss). | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alopecia, Hair loss, Hair disease, CTP-543