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

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT03359356
• Collaborator: Rockefeller University (Other), Regeneron Pharmaceuticals (Industry), Sanofi (Industry)
• Enrollment: 60
• Locations: 2
• Arms: 2
• Actual Duration (Months): 35.3
• Patients Per Site: 30
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alopecia Areata	Drug: Dupilumab; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Defining Reversal of Alopecia Areata (AA) Phenotype With Dupilumab in Patients With and Without Associated Atopic Dermatitis (AD)
• Actual Study Start Date: Jan 9, 2018
• Actual Primary Completion Date: Jan 14, 2020
• Actual Study Completion Date: Dec 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dupilumab An initial dupilumab dose of 600 mg (two 300 mg subcutaneous injections), followed by dupilumab 300 mg given every week	Drug: Dupilumab; A total of 24 doses; Other Names: Dupixent
Placebo Comparator: Placebo Matching placebo in prefilled syringes identical to the dupilumab syringes	Drug: Placebo; A total of 24 doses; Other Names: matching placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 24 [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.

Secondary Outcome Measures

1. Change From Week 24 in the SALT Score at Week 48 [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.

2. Change From Baseline in the SALT Score at Week 48 [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.

3. 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 [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.

4. Number of Patients Achieving at Least 75% Improvement in SALT-75 at Weeks 24 and 48 [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.

5. Number of Patients Achieving at Least 90% Improvement in Severity of Alopecia Tool (SALT) Score (SALT-90) at Weeks 24 and 48 [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

6. Change in Alopecia Areata Symptom Impact Scale (AASIS) [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.

7. Change in Alopecia Areata Quality of Life Questionnaire [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).

8. Eyelash/Eyebrow Assessment Score Weeks 12, 24, 36, and 48 Compared to Baseline [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).

9. Change in EASI Scores From Baseline at Week 24 and 48 [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.

10. Number of Adverse Events [48 weeks]

    Safety profile of dupilumab in subjects with AA by reported adverse effects, physical examinations and laboratory parameters

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
2	The Rockefeller University Laboratory for Investigative Dermatology	New York	New York	United States	10065-6399

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai
• Rockefeller University
• Regeneron Pharmaceuticals
• Sanofi

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 8, 2020

More Information

Publications

None provided.

• Responsible Party: Emma Guttman, Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03359356
• Other Study ID Numbers: GCO 17-1084
• First Posted: Dec 2, 2017
• Last Update Posted: Feb 14, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Keywords provided by Emma Guttman, Professor, Icahn School of Medicine at Mount Sinai: alopecia; alopecia areata; alopecia universalis; alopecia totalis; dupixent; dupilumab
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Alopecia; Alopecia Areata

Study Results

Participant Flow

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Placebo given Weeks 0-24, then Dupilumab given Weeks 24-48 Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Period Title: Overall Study
STARTED	20	40
COMPLETED	20	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo Then Dupilumab	Dupilumab	Total
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.	Total of all reporting groups
Overall Participants	20	40	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.5 (14.4)	41.6 (13.8)	43 (13)
Sex: Female, Male (Count of Participants)
Female	13 65%	30 75%	43 71.7%
Male	7 35%	10 25%	17 28.3%
Race/Ethnicity, Customized (Count of Participants)
White	15 75%	31 77.5%	46 76.7%
African American	2 10%	3 7.5%	5 8.3%
Asian	2 10%	6 15%	8 13.3%
Other	1 5%	0 0%	1 1.7%
Duration since last hair regrowth (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.5 (3)	3.8 (2.9)	3.6 (3)
Severity of alopecia tool (SALT) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	75.4 (26.1)	70.5 (27.6)	72.1 (27)
Patients with SALT>75 (Count of Participants)
Count of Participants [Participants]	12 60%	20 50%	32 53.3%
Patients with SALT<75 (Count of Participants)
Count of Participants [Participants]	8 40%	20 50%	28 46.7%
Patients with Alopecia Totalis/Universalis (Count of Participants)
Count of Participants [Participants]	8 40%	13 32.5%	21 35%
Alopecia Areata Symptom Impact Scale (AASIS) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	56.1 (32.86)	48.42 (30.27)	50.9 (31.33)
Alopecia Areata Quality of Life (AA-QoL) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	51.75 (13.88)	49.49 (12.56)	50.25 (13.1)
Eyelash assessment (Count of Participants)
Very prominent	6 30%	12 30%	18 30%
Prominent	2 10%	6 15%	8 13.3%
Moderate	1 5%	4 10%	5 8.3%
Minimal	6 30%	9 22.5%	15 25%
None	4 20%	9 22.5%	13 21.7%
Eyebrow assessment (Count of Participants)
Very prominent	6 30%	10 25%	16 26.7%
Prominent	0 0%	5 12.5%	5 8.3%
Moderate	2 10%	6 15%	8 13.3%
Minimal	8 40%	9 22.5%	17 28.3%
None	4 20%	10 25%	14 23.3%
Patients with atopic dermatitis (AD) history (Count of Participants)
Count of Participants [Participants]	6 30%	17 42.5%	23 38.3%
Patients with active AD (Count of Participants)
Count of Participants [Participants]	2 10%	5 12.5%	7 11.7%
Eczema area and severity index (EASI) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	27.4 (11.0)	13.58 (5.68)	17.53 (9.83)
Patients with family history of atopy (Count of Participants)
Count of Participants [Participants]	9 45%	18 45%	27 45%
IgE (IU/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [IU/ml]	342.5 (826.7)	525.8 (1211.3)	464.7 (1094)
Patients with IgE≥200 (Count of Participants)
Count of Participants [Participants]	5 25%	13 32.5%	18 30%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 24
Description	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.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Mean (Standard Deviation) [score on a scale]	-6.3 (4.2)	2.3 (3)

2. Secondary Outcome

Title	Change From Week 24 in the SALT Score at Week 48
Description	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.
Time Frame	Week 24 and 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Mean (Standard Error) [score on a scale]	-6.3 (4.2)	2.3 (3)

3. Secondary Outcome

Title	Change From Baseline in the SALT Score at Week 48
Description	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.
Time Frame	Baseline and 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Mean (Standard Error) [score on a scale]	-6.3 (4.2)	2.3 (3)

4. Secondary Outcome

Title	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
Description	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.
Time Frame	weeks 24 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks, an initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 24 doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week, A total of 24 doses
Measure Participants	20	40
Week 24	0 0%	4 10%
Week 48	3 15%	9 22.5%

5. Secondary Outcome

Title	Number of Patients Achieving at Least 75% Improvement in SALT-75 at Weeks 24 and 48
Description	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.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Week 24	0 0%	2 5%
Week 48	1 5%	6 15%

6. Secondary Outcome

Title	Number of Patients Achieving at Least 90% Improvement in Severity of Alopecia Tool (SALT) Score (SALT-90) at Weeks 24 and 48
Description	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
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.), followed by 300 mg given every other week, A total of 24 doses
Measure Participants	20	40
Week 24	0 0%	1 2.5%
Week 48	1 5%	4 10%

7. Secondary Outcome

Title	Change in Alopecia Areata Symptom Impact Scale (AASIS)
Description	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.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. A total of 24 doses	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week, A total of 24 doses
Measure Participants	20	40
Week 24	10.25 (20.29)	0.64 (22.27)
Week 48	22.6 (35.42)	8.13 (27.65)

8. Secondary Outcome

Title	Change in Alopecia Areata Quality of Life Questionnaire
Description	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).
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Week 24	4.29 (9.14)	2.06 (8.49)
Week 48	22.6 (35.42)	8.13 (27.65)

9. Secondary Outcome

Title	Eyelash/Eyebrow Assessment Score Weeks 12, 24, 36, and 48 Compared to Baseline
Description	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).
Time Frame	Weeks 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

One participant had missing eyelash data because of artificial eyelashes (glued on her real eyelashes).

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Eyelash Week 12	0 (0.37)	0.07 (0.24)
Eyelash Week 24	0.37 (0.34)	0.04 (0.24)
Eyelash Week 36	-0.15 (0.37)	-0.06 (0.27)
Eyelash Week 48	-0.17 (0.35)	0.05 (0.26)
Eyebrow Week 12	0.09 (0.37)	0.21 (0.25)
Eyebrow Week 24	0.27 (0.34)	0.19 (0.24)
Eyebrow Week 36	-0.2 (0.34)	0.17 (0.24)
Eyebrow Week 48	-0.03 (0.35)	0.09 (0.25)

10. Secondary Outcome

Title	Change in EASI Scores From Baseline at Week 24 and 48
Description	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.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Data for only those participants with eczema.

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	2	3
Week 24	-1.45 (3.61)	10.6 (3.64)
Week 48	23.9 (10.61)	10.53 (3.75)

11. Secondary Outcome

Title	Number of Adverse Events
Description	Safety profile of dupilumab in subjects with AA by reported adverse effects, physical examinations and laboratory parameters
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Then Dupilumab	Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.	An initial dose of 600 mg (two 300 mg subcutaneous injections), followed by 300 mg given every other week. A total of 48 Dupilumab doses will be given throughout the clinical trial, including 24 weeks during a randomized period and 24 weeks during an open label period.
Measure Participants	20	40
Number [events]	24	9

Adverse Events

Time Frame	48 weeks
Arm/Group Title	Placebo		Dupilumab
Arm/Group Description	Matching placebo in prefilled syringes identical to the dupilumab syringes. 24 weeks of Placebo		Matching placebo in prefilled syringes identical to the dupilumab syringes. After 24 weeks of Placebo, an initial dose of 600 mg Dupilumab (two 300 mg subcutaneous injections), followed by an open-label period in which 300 mg given every other week. A total of 24 Dupilumab doses.
All Cause Mortality
	Placebo		Dupilumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/40 (0%)
Serious Adverse Events
	Placebo		Dupilumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		1/40 (2.5%)
Renal and urinary disorders
Bladder Cancer	0/20 (0%)	0	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Dupilumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/20 (20%)		22/40 (55%)
Gastrointestinal disorders
Gastrointestinal symptoms	1/20 (5%)	1	3/40 (7.5%)	3
General disorders
Fall	1/20 (5%)	1	0/40 (0%)	0
Fatigue	0/20 (0%)	0	1/40 (2.5%)	1
Infections and infestations
Facial rash	0/20 (0%)	0	1/40 (2.5%)	1
Upper respiratory tract infection	2/20 (10%)	2	6/40 (15%)	6
Urinary tract infection	0/20 (0%)	0	2/40 (5%)	2
Oral herpes	1/20 (5%)	1	0/40 (0%)	0
Musculoskeletal and connective tissue disorders
Other orthopedic injuries/procedures	1/20 (5%)	1	5/40 (12.5%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder malignancy	0/20 (0%)	0	1/40 (2.5%)	1
Prostatic hyperplasia	0/20 (0%)	0	1/40 (2.5%)	1
Skin and subcutaneous tissue disorders
Injection site reaction	0/20 (0%)	0	2/40 (5%)	2
Eosinophilic dermatitis	0/20 (0%)	0	1/40 (2.5%)	1
Conjuctivitis	0/20 (0%)	0	4/40 (10%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.