Study of DAXDILIMAB for the Treatment of Moderate-to-Severe Alopecia Areata

Study Overview
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Brief Summary
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The purpose of this study is to assess the preliminary efficacy, safety, tolerability, PK, and PD of Daxdilimab in participants with moderate to severe AA, with ≥50% and ≤95% total scalp hair loss as defined by the SALT score at Screening and Day 1.

Detailed Description
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Approximately 30 participants will be enrolled to receive daxdilimab administered subcutaneously over 32 weeks. The maximum trial duration per participant is approximately 52 weeks, including up to 30 days for the screening period, 32 weeks for the open-label treatment period where participants will receive daxdilimab and approximately 16 weeks for the follow-up period. Safety evaluations will be performed regularly throughout the course of the study.

Official Title
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A Phase 2A, Open Label, Proof of Concept Trial of Daxdilimab for the Treatment of Moderate To Severe Alopecia Areata

Conditions
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Alopecia Areata

Intervention / Treatment
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* Biological: Daxdilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give informed consent. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial. Adult men or women 18 to 65 years of age. Willing to keep the same hair style and color (eg, hair products, process, and timing for hair appointments) for the duration of the trial. Clinical diagnosis of moderate-to-severe AA - defined as meeting the following criteria: Presence of ≥ 50% and ≤ 95% total scalp hair loss at screening and baseline (Day 1) defined by the SALT score. Duration of current episode of hair loss >3 months but <7 years at screening and Day 1, along with investigators' assessment that hair regrowth is possible. No evidence of active regrowth present at baseline and no known history of significant regrowth, as per investigator's judgement, over the last 6 months. Exclusion Criteria: Individuals involved in the conduct of the trial, their employees, or immediate family members of such individuals. Any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with the evaluation of the IP or interpretation of trial results. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a previous monoclonal antibody (mAb) or human immunoglobulin (Ig) therapy. Participant has had excessive sun exposure, is planning a trip to a sunny climate, or has used tanning booths within 4 weeks prior to Day 1 or is not willing to minimize natural and artificial sunlight exposure during the trial. Use of sunscreen products and protective apparel are recommended when sun exposure cannot be avoided. Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection, splenectomy, or any underlying condition that in the opinion of the investigator significantly predisposes the participant to infection. Confirmed positive test for hepatitis B serology defined as: Hepatitis B surface antigen (HBsAg), or Hepatitis B core antibody (HBcAb or anti-HBc) Positive test for hepatitis C virus antibody. Active tuberculosis (TB), or a positive TB test at Screening. Participant will be evaluated for latent TB infection with a purified protein derivative (PPD) test or a QuantiFERON-TB Gold test. Participants who demonstrate evidence of latent TB infection (either PPD ≥5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of bacille Calmette-Guérin vaccination status will not be allowed to participate in the trial, unless documented history of appropriate treatment for active or latent TB. Participants with an indeterminate test result can repeat the test, but if the repeat test is also indeterminate, they are excluded. Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus [CMV]) at any time prior to Day 1, including, but not limited to, disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the last 2 years), or ophthalmic herpes. Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to Day 1. Any of the following within 30 days prior to signing the ICF and though Day 1: Clinically significant active infection in the opinion of the investigator, including ongoing, and chronic infection requiring antibiotics or antiviral medication (chronic nail infections are allowed). Note: Participant with a limited recurrence of a cold sore or herpes genitalis between ICF signature and Day 1 could be eligible based on the investigator's judgement. Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives. A participant with a documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test may be rescreened at least 2 weeks after a positive test if the participant is asymptomatic and at least 3 weeks after resolution of symptomatic Coronavirus Disease 2019 (COVID-19) illness. Opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within 2 years prior to Day 1. Any acute illness or evidence of clinically significant active infection, such as fever ≥ 38.0°C (≥ 100.5°F) on Day 1. History of clinically significant cardiac disease including unstable angina; myocardial infarction within 6 months prior to Day 1; congestive heart failure; arrhythmia requiring active therapy, except for clinically insignificant extra systoles, or minor conduction abnormalities; or presence of clinically significant abnormality on ECG if, in the opinion of the investigator, it would increase the risk of trial participation. History of cancer or lymphoproliferative disease within 5 years prior to Day 1, except as follows: In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to Screening, or Nonmetastatic cutaneous basal cell or squamous cell carcinoma of the skin treated with apparent success with curative therapy. Active forms of other inflammatory skin disease(s) or evidence of other skin conditions (eg, psoriasis, seborrheic dermatitis, lupus) at the time of the Screening and through Day 1, that in the opinion of the investigator might interfere with evaluation of AA and the assessment of the activity measures. Presence of another form of alopecia (except for androgenic alopecia). History of male or female pattern hair loss > Hamilton stage III or > Ludwig stage II. History or presence of hair transplants. History or presence of micropigmentation of the scalp (Note: microblading of the eyebrows is permitted). Use of steroids (systemic and intralesional), anthralin, squaric acid, diphenylcycloprophenone (DPCP), dinitrochlorobenzene (DCNB), protopic, minoxidil, or any other medication which in the opinion of the investigator may affect hair regrowth within 4 weeks of Day 1 visit. Note: Intranasal and inhaled corticosteroids are allowed, eye and ear drops containing corticosteroids are also allowed. Use of platelet-rich plasma injections in the last 12 weeks prior to Day 1. Topical medicated treatment that could affect AA including, but not limited to, topical corticosteroids, calcineurin inhibitors, antimicrobials, medical devices within 2 weeks of Day 1 visit. Note: Topical corticosteroids are permitted outside of the scalp, eyebrows, and eyelids. Participants who have had previous treatment with any biologic B-cell-depleting therapy (eg, rituximab, ocrelizumab, or ofatumumab) or other B-cell targeting therapy (eg, belimumab) within 12 months before Day 1. Participants who have received previous treatment with pDC inhibiting therapies (eg, anti-ILT7, anti-blood dendritic cell antigen 2 [BDCA2]). Inadequate response to adequate trial of oral Janus Kinase (JAK) inhibitors. Previous exposure to topical JAK inhibitors is acceptable, regardless of response. Any biologic or conventional disease-modifying antirheumatic drugs (DMARD), immunosuppressant (eg, cyclosporine, methotrexate, or azathioprine), JAK-inhibitors, interferon (IFN) blocking therapies, or antiproliferative agents, if last dose was taken: a. within 8 weeks prior to Day 1 or b. drug-specific 5 half-lives elimination period (if longer than 8 weeks). Participant has received any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to Day 1. Currently receiving a nonbiological IP or device or has received one within 4 weeks prior to Day 1 or within 5 published half-lives, whichever is longer. Participant has received any ultraviolet (UV)-B phototherapy (including tanning beds), has had psoralen-UV-A (PUVA) treatment, or excimer laser within 4 weeks prior to Day 1.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daxdilimab<br>Nine sets of Daxdilimab injections over a total of 32 weeks. | Biological: Daxdilimab<br>* Daxdilimab will be administered subcutaneously as two injections for each dose.<br>* Other names: HZN-7734;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in Severity of Alopecia Tool (SALT) score at Week 24. |  | Day 1 through Week 24. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in Severity of Alopecia Tool (SALT) score at Weeks 12-20; 28-36. |  | Weeks 12-20; 28-36 | 
| Proportion of participants who achieve ≥50% reduction in Severity of Alopecia Tool (SALT) from baseline at Weeks 12-36. |  | Weeks 12-36 | 
| Proportion of participants with absolute Severity of Alopecia Tool (SALT) score ≤ 10, 20, 30, 50 at Weeks 12-36. |  | Weeks 12-36 | 
| Percent change from baseline in Severity of Alopecia Tool (SALT) score at Weeks 40-48. |  | Weeks 40-48 | 
| Proportion of participants who achieve ≥50% reduction in Severity of Alopecia Tool (SALT) from baseline at Weeks 40-48. |  | Weeks 40-48 | 
| Proportion of participants with absolute Severity of Alopecia Tool (SALT) score ≤ 10, 20, 30, 50 at Weeks 40-48. |  | Weeks 40-48 | 
| Change from baseline in plasmacytoid dendritic cells (pDCs). |  | Day 1 to 48 Weeks | 
| Anti-drug antibody (ADA) rate. |  | Day 1 to 48 Weeks | 
| Incidence of treatment-emergent adverse events (TEAEs), treatment-serious adverse events (TESAEs), and adverse events of special interest (AESIs). |  | Day 1 to 48 Weeks |