Treatment of Alopecia Areata (AA) With Dupilumab in Patients With and Without Atopic Dermatitis (AD)

• ClinicalTrials.gov Identifier: NCT03359356
• Recruitment Status: Completed
• First Posted: December 2, 2017
• Results First Posted: February 14, 2022
• Last Update Posted: September 13, 2022
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Rockefeller University; Regeneron Pharmaceuticals; Sanofi
• Information provided by (Responsible Party): Emma Guttman, Icahn School of Medicine at Mount Sinai

Tracking Information

• First Submitted Date: November 27, 2017
• First Posted Date: December 2, 2017
• Results First Submitted Date: August 17, 2021
• Results First Posted Date: February 14, 2022
• Last Update Posted Date: September 13, 2022
• Actual Study Start Date: January 9, 2018
• Actual Primary Completion Date: January 14, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2022)

Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 24 [ Time Frame: Baseline and 24 weeks ]

The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. Primary Outcome is baseline minus Week 24 value.

Original Primary Outcome Measures (submitted: November 27, 2017)

• Change in SALT score (SALT50) [ Time Frame: Baseline and 24 weeks ]
  Proportion of patients achieving at least 50% improvement in Severity of Alopecia Tool (SALT) score (SALT-50) at Weeks 24 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas.
• Change in SALT50 [ Time Frame: Baseline and 48 weeks ]
  Proportion of patients achieving at least 50% improvement in SALT-50 score 48 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas.

Current Secondary Outcome Measures (submitted: January 18, 2022)

• Change From Week 24 in the SALT Score at Week 48 [ Time Frame: Week 24 and 48 weeks ]
  SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. Week 24 minus week 48 value.
• Change From Baseline in the SALT Score at Week 48 [ Time Frame: Baseline and 48 weeks ]
  Change in SALT score at Week 48 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. Baseline minus week 48 value.
• Number of Patients Achieving at Least 50% Improvement in Severity of Alopecia Tool (SALT) Score (SALT-50) at Weeks 24 and 48 Compared to Baseline [ Time Frame: weeks 24 and 48 ]
  Number of subjects achieving SALT-50 score at Weeks 24 and 48 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss.in all areas.
• Number of Patients Achieving at Least 75% Improvement in SALT-75 at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  Number of patients with Severity of Alopecia Tool (SALT) Score (SALT-75) (> or equal to 75% improvement in SALT score) at Weeks 24 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss.
• Number of Patients Achieving at Least 90% Improvement in Severity of Alopecia Tool (SALT) Score (SALT-90) at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  The number of patients achieving at least 90% improvement in Severity of Alopecia Tool (SALT) score (SALT-90) at Weeks 24, 48 compared to Baseline
• Change in Alopecia Areata Symptom Impact Scale (AASIS) [ Time Frame: Weeks 24 and 48 ]
  Change in AASIS at Weeks 24 and 48 compared to Baseline. AASIS is a 13-item instrument, each item scored from 0 to 10 where higher scores correspond to worse symptom impact, full range from 0 to 130.
• Change in Alopecia Areata Quality of Life Questionnaire [ Time Frame: Weeks 24 and 48 ]
  Change in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 24 and 48 compared to baseline. AAQoL is a 21-item instrument scored from 0 (poor) to 100 (good).
• Eyelash/Eyebrow Assessment Score Weeks 12, 24, 36, and 48 Compared to Baseline [ Time Frame: Weeks 12, 24, 36, and 48 ]
  Change in eyelash and eyebrow scores at Weeks 12, 24, 36, and 48 compared to baseline. The Eyelash/Eyebrow Assessment score based on a 5-point scale, ranging from 0 (none) to 4 (very prominent eyelashes/eyebrows).
• Change in EASI Scores From Baseline at Week 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  Change from baseline in Eczema Area and Severity Index (EASI) at Weeks 24 and 48. EASI scores range from 0 (no symptoms) to 72 (severe eczema) with lower score indicating better health outcomes/less eczema.
• Number of Adverse Events [ Time Frame: 48 weeks ]
  Safety profile of dupilumab in subjects with AA by reported adverse effects, physical examinations and laboratory parameters

Original Secondary Outcome Measures (submitted: November 27, 2017)

• Change in SALT Score [ Time Frame: Baseline and 24 weeks ]
  Percent change in SALT score at Weeks 24 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas.
• Percent change in SALT [ Time Frame: Baseline and 48 weeks ]
  Percent change in SALT score at Weeks 48 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas.
• Change in SALT75 [ Time Frame: Baseline and 72 weeks ]
  Proportion of patients with SALT-75 (> or equal to 75% improvement in SALT score) at Weeks 72 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas.
• Change in SALT50 [ Time Frame: Baseline and 72 weeks ]
  Proportion of patients with SALT-50 (> or equal to 50% improvement in SALT score) at Weeks 72 compared to Baseline. SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas.
• Change in Alopecia Areata Symptom Impact Scale (AASIS) [ Time Frame: Baseline and 24 weeks ]
  Change in AASIS at Weeks 24 compared to Baseline. AASIS is a 13-item instrument, each item scored from 0 to 10 where higher scores correspond to worse symptom impact, full range from 0 to 130.
• Change in Alopecia Areata Symptom Impact Scale (AASIS) [ Time Frame: Baseline and 48 weeks ]
  Change in AASIS at Weeks 48 compared to Baseline. AASIS is a 13-item instrument, each item scored from 0 to 10 where higher scores correspond to worse symptom impact, full range from 0 to 130.
• Percent change in Alopecia Areata Quality of Life questionnaire [ Time Frame: Baseline and 24 weeks ]
  Percent change in Alopecia Areata Quality of Life (AAQoL) at Weeks 24 compared to baseline. AAQoL is a 21-item instrument scored from 0 (poor) to 100 (good).
• Percent change in AAQoL [ Time Frame: Baseline and 48 weeks ]
  Percent change in AAQoL at Weeks 48 compared to baseline. AAQoL is a 21-item instrument, each time scored from 0 to 4. The scores are adjusted to produce a full range from 0 to 100 where higher scores refer to worse QoL.
• Change in Salt subclass score [ Time Frame: Baseline and 24 weeks ]
  Semi-quantitative score using SALT subclasses (0 = no hair loss; 1 = <25% hair loss; 2 = 25-49% hair loss; 3 = 50-75% hair loss; 4 = 75-99% hair loss; 5 = 100% hair loss) at weeks 24 compared to baseline
• Change in Salt subclass score [ Time Frame: Baseline and 48 weeks ]
  Semi-quantitative score using SALT subclasses (0 = no hair loss; 1 = <25% hair loss; 2 = 25-49% hair loss; 3 = 50-75% hair loss; 4 = 75-99% hair loss; 5 = 100% hair loss) at weeks 48 compared to baseline
• Investigator's Global Assessment (IGA) [ Time Frame: Week 48 ]
  The aaPGA is used to assess the clinical response to treatment based on a 6-point scale ranging from 0 (no regrowth) to 5 (100% regrowth).
• Change in the Eyelash/Eyebrow Assessment score [ Time Frame: Baseline and 48 weeks ]
  The Eyelash/Eyebrow Assessment score based on a 5-point scale, ranging from 0 (none) to 4 (very prominent eyelashes/eyebrows)
• Change in Eczema Area and Severity Index (EASI90) [ Time Frame: Baseline and 48 weeks ]
  Proportion of patients with EASI90 (> of equal to 90% reduction from baseline EASI score) at 48 weeks compared to baseline. The EASI is used to assess the severity and extent of AD. Four AD disease characteristics will be assessed (0 = absent to 3 = severe). Area of AD involvement will be assessed as a percentage by involved body area of the head, trunk, arms, and legs, and converted to a score of 0 to 6.
• Change in Eczema Area and Severity Index (EASI75) [ Time Frame: Baseline and 48 weeks ]
  Proportion of patients with EASI75 (> of equal to 75% reduction from baseline EASI score) at 48 weeks compared to baseline. The EASI is used to assess the severity and extent of AD. Four AD disease characteristics will be assessed (0 = absent to 3 = severe). Area of AD involvement will be assessed as a percentage by involved body area of the head, trunk, arms, and legs, and converted to a score of 0 to 6.
• Change in Eczema Area and Severity Index (EASI50) [ Time Frame: Baseline and 48 weeks ]
  Proportion of patients with EASI50 (> of equal to 50% reduction from baseline EASI score) at 48 weeks compared to baseline. The EASI is used to assess the severity and extent of AD. Four AD disease characteristics will be assessed (0 = absent to 3 = severe). Area of AD involvement will be assessed as a percentage by involved body area of the head, trunk, arms, and legs, and converted to a score of 0 to 6.
• Number of Adverse events [ Time Frame: 72 weeks ]
  Safety profile of dupilumab in subjects with AA by reported by number adverse effects

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of Alopecia Areata (AA) With Dupilumab in Patients With and Without Atopic Dermatitis (AD)
• Official Title: Defining Reversal of Alopecia Areata (AA) Phenotype With Dupilumab in Patients With and Without Associated Atopic Dermatitis (AD)
• Brief Summary: Alopecia areata is a medical condition, in which the hair falls out in patches. The hair can fall out on the scalp or elsewhere on the face and body. Alopecia areata is an autoimmune skin disease, which means that the immune system is recognizing the hair follicles as foreign and attacking them, causing round patches of hair loss. It can progress to total scalp hair loss (alopecia totalis) or complete body hair loss (alopecia universalis). The scalp is the most commonly affected area, but the beard or any hair-bearing site can be affected alone or together with the scalp. Alopecia areata occurs in males and females of all ages, and is a highly unpredictable condition that tends to recur. Alopecia areata can cause significant distress to both patients and their families. In this study, the aim is to assess the effects of dupilumab in patients with alopecia areata.

Detailed Description

The purpose of this study is to assess whether dupilumab can be a helpful treatment for alopecia areata.

This is a randomized, double-blind, placebo-controlled pilot study of a total of 54 subjects with moderate to severe alopecia areata involving 30-100% of the scalp. The researchers expect one third of these subjects to have concomitant alopecia areata (AA) and atopic dermatitis (AD).

The researchers' experience in AD, and past experience in psoriasis showed that biomarker studies in skin tissues are critical to the understanding of key pathogenic pathways that are upregulated in each disease and how well they are suppressed with effective treatment. These mechanistic studies coupled with clinical trials are key in the disease to shed light on important disease mechanisms, and to explain which molecules are suppressed by each therapeutic target. Data shows that IL-13 is significantly upregulated in both AD and AA lesions compared to nonlesional skin. It is very important to associate the clinical responses with suppression of this cytokine and related molecules as well as other pathway cytokines in skin tissues. Both the whole genomic profiling and individual molecular and cellular markers are very important in order to understand how well anti-IL-13 will change/suppress AA-associated pathways and compare with those that will be suppressed in AD.

Since this study is designed to gain basic knowledge rather than to yield information directly related to patient care, the results are not entered in the participants' medical records. If, at a later date, correlations of in-vitro tests and the patients' clinical situation suggest that the results do bear on the patients' health, an amended protocol will be submitted to the IRB so that results can be made available to the medical record.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alopecia Areata

Intervention

• Drug: Dupilumab
  A total of 24 doses
  Other Name: Dupixent
• Drug: Placebo
  A total of 24 doses
  Other Name: matching placebo

Study Arms

• Experimental: Dupilumab
  An initial dupilumab dose of 600 mg (two 300 mg subcutaneous injections), followed by dupilumab 300 mg given every week
  Intervention: Drug: Dupilumab
• Placebo Comparator: Placebo
  Matching placebo in prefilled syringes identical to the dupilumab syringes
  Intervention: Drug: Placebo

• Publications *: Guttman-Yassky E, Renert-Yuval Y, Bares J, Chima M, Hawkes JE, Gilleaudeau P, Sullivan-Whalen M, Singer GK, Garcet S, Pavel AB, Lebwohl MG, Krueger JG. Phase 2a randomized clinical trial of dupilumab (anti-IL-4Ralpha) for alopecia areata patients. Allergy. 2022 Mar;77(3):897-906. doi: 10.1111/all.15071. Epub 2021 Sep 6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 23, 2020): 60
• Original Estimated Enrollment (submitted: November 27, 2017): 54
• Actual Study Completion Date: December 17, 2020
• Actual Primary Completion Date: January 14, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female subjects who are at least 18 years old at the time of informed consent.
• Subject is able to understand and voluntarily sign an informed consent document prior to participation
• Subject is able to adhere to the study visit schedule and other protocol requirements.

• Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product (IP), FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

  1. Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR
  2. Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
• If subject is a female of non-childbearing potential, she must have documented history of infertility, be in a menopausal state for one year, or had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy.

• Subject has a history of at least 6 months of moderate to severe AA (≥ 30% scalp involvement) as measured using the SALT score; OR subject has ≥ 95% loss of scalp hair for enrollment as AA totalis (AT) or universalis (AU) subtypes.

  1. AT and AU will be limited to 50% of the total number of subjects enrolled.
  2. One-third of subjects must have active AD skin or a concomitant history of AD at the time of the Screening and Baseline visits.
• Subject has a negative Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) prior to baseline. Subjects with a positive or indeterminable PPD or QFT result must have a documented negative workup for tuberculosis and/or completed standard tuberculosis therapy.

• Subjects must meet the following laboratory criteria:

  1. White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (≤ 14 x 109/L).
  2. Platelet count ≥ 100,000/μL (≥ 100 x 109/L).
  3. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L).
  4. AST (SGOT) and ALT (SGPT) ≤ 2 x upper limit of normal (ULN). If the initial test shows ALT or AST > 2 times the ULN, one repeat test is allowed during the Screening Phase.
  5. Total bilirubin ≤ 2 mg/dL (34 μmol/L). If the initial test shows total bilirubin > 2 mg/dL (34 μmol/L), one repeat test is allowed during the Screening Phase.
  6. Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L).
• Subject is judged to be in otherwise good overall health following a detailed medical and medication history, physical examination, and laboratory testing.

Exclusion Criteria:

• Subject is pregnant or breastfeeding.
• Subject's cause of hair loss is indeterminable and/or they have concomitant causes of alopecia, such traction, cicatricial, pregnancy-related, drug-induced, telogen effluvium, or advanced androgenetic alopecia (i.e. Ludwig Type III or Norwood-Hamilton Stage ≥ V).
• Subject has a history of AA with no evidence of hair regrowth for ≥ 10 years since their last episode of hair loss.
• Subject has an active bacterial, viral, or helminth parasitic infections; OR a history of ongoing, recurrent severe infections requiring systemic antibiotics
• Subject with a known or suspected underlying immunodeficiency or immune-compromised state as determined by the investigator.
• Subject has a concurrent or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, intestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
• Active hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or positive HIV serology at the time of screening for subjects determined by the investigators to be at high-risk for this disease.
• Subject has a suspected or active lymphoproliferative disorder or malignancy; OR a history of malignancy within 5 years before the Baseline assessment, except for completely treated in situ non-melanoma skin and cervical cancers without evidence of metastasis.
• Subject has received a live attenuated vaccine ≤ 30 days prior to study randomization.
• Subject has any uncertain or clinically significant laboratory abnormalities that may affect interpretation of study data or endpoints.
• Subject has any other medical or psychological condition that, in the opinion of the investigator, may present additional unreasonable risks as a result of their participation in the study and/or interfere with clinic visits and necessary study assessments.
• History of adverse systemic or allergic reactions to any component of the study drug.
• Severe, untreated asthma or a history of life-threatening asthma exacerbations while on appropriate anti-asthmatic mediations.
• Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus, or ultraviolet (UV) phototherapy with/without Psoralen Ultraviolet A (PUVA) therapy within 4 weeks prior to randomization.
• Use of an oral JAK inhibitor (tofacitinib, ruxolitinib) within 12 weeks prior to the Baseline visit.
• Subject has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus within 1 week before the Baseline visit.
• Subject has been previously treated with dupilumab.
• Subject currently uses or plans to use anti-retroviral therapy at any time during the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03359356
• Other Study ID Numbers: GCO 17-1084
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Since this study is designed to gain basic knowledge rather than to yield information directly related to patient care, the results are not entered in the participants' medical records. If, at a later date, correlations of in-vitro tests and the patients' clinical situation suggest that the results do bear on the patients' health, an amended protocol will be submitted to the IRB so that results can be made available to the medical record.

• Current Responsible Party: Emma Guttman, Icahn School of Medicine at Mount Sinai
• Original Responsible Party: Emma.Guttman, Icahn School of Medicine at Mount Sinai, Professor
• Current Study Sponsor: Icahn School of Medicine at Mount Sinai
• Original Study Sponsor: Same as current

Collaborators

• Rockefeller University
• Regeneron Pharmaceuticals
• Sanofi

Investigators

• Principal Investigator: Emma Guttman, MD,PhD; Icahn School of Medicine at Mount Sinai

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: August 2022