Treatment of Alopecia Areata (AA) With Dupilumab in Patients With and Without Atopic Dermatitis (AD)
Condition: Alopecia Areata
MeSH terms: Dermatitis, Atopic; Dermatitis; Alopecia; Alopecia Areata
Intervention: Dupilumab; Placebo
Intervention description: A total of 24 doses; A total of 24 doses
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: alopecia; alopecia areata; alopecia universalis; alopecia totalis; dupixent; dupilumab

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.
    

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.