Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata

Alopecia areata (AA) 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 to assess the effects of a new treatment called apremilast in patients with alopecia areata. A total of 30 patients will be included in the study, which will run for a total of 52 weeks.

This is a randomized, double-blind, placebo-controlled pilot study consisting of two phases. A total of 30 subjects with moderate to severe alopecia areata (including universalis and totalis) involving 50-100% of the scalp will be enrolled. A possible maximum of 15 patients (approximately 7 patients each) with current episodes of AA totalis / universalis may be included in this study.

In Phase 1, subjects will be randomized (2:1) to either receive apremilast or placebo for 24 weeks.

In Phase 2, eligible subjects will receive apremilast from Week 24 through Week 48. The following subjects will be eligible to enter into Phase 2:

1. Subjects who received placebo in Phase 1 of the study
2. Subjects who received apremilast in Phase 1 of the study, and who achieved a minimum of 50% regrowth (SALT50) at Week 24, compared to Baseline.

Eligibility Criteria:
Inclusion Criteria:

Males or females, 18 years or older at the time of signing the informed consent document.

Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted.

Able to adhere to the study visit schedule and other protocol requirements. Subject with a diagnosis of patchy scalp alopecia areata present for at least 6 months, and up to a maximum of 10 years.

Patients with ≥50% and \<95% total scalp hair loss at Baseline as measured using the SALT score to qualify as moderate to severe AA; and 95%-100% scalp hair loss to qualify as AA totalis/universalis.

Must meet the following laboratory criteria White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and \< 14,000/mm3 (\< 14 x 109/L). Platelet count ≥ 100,000/μL (≥ 100 x 109/L). Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L). 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.

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.

Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L).

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:

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

Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]); plus spermicide PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]) while on IP and for at least 28 days after the last dose of IP.

No evidence of hair regrowth present at Baseline.

EXCLUSION CRITERIA:

The presence of any of the following will exclude a subject from enrollment:

Clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, or immunologic disease, or other major uncontrolled diseases that will affect the health of the subject during the study or interfere with the interpretation of study results.

Hepatitis B surface antigen positive at Screening (Visit 1). Hepatitis C antibody positive at Screening (Visit 1). History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency \[CVID\]). Subjects deemed at risk by the study investigator, may also undergo testing for human immunodeficiency virus (HIV). Subjects deemed at risk include those with a history of injection drug use, homosexual subjects, and subjects with known sexual contact with an HIV positive partner.

Active TB or a history of inadequately treated TB. Active substance abuse or a history of substance abuse within six months prior to Screening.

Pregnant or breast feeding. History of allergy to any component of the IP.

Major surgery within eight weeks prior to Screening (Visit 1) and/or planned surgery during the length of the study.

Malignancy or history of malignancy, except for:

treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years prior to Screening (Visit 1).

Unstable asthma (eg, acute episodes of exacerbation \[nocturnal episodes, sudden episodes triggered by unidentifiable factors\] despite a stable regimen of anti-asthmatic medications); prior episode(s) of life-threatening asthma; or asthma that requires inhaled budesonide or equivalent at \>1200 μg/day or fluticasone propionate at \> 880 μg/day along with another anti-asthmatic drug such as a long-acting beta-agonist.

A history of and/or concurrent condition of serious hypersensitivity (eg, anaphylaxis) to drugs, foods, or other allergens without access to emergency rescue medication such as epinephrine.

Persistent or recurring bacterial infection requiring systemic antibiotics, or clinically significant viral or fungal infections, within two weeks of Screening (Visit 1). Any treatment for such infections must have been completed at least two weeks prior to the Screening Visit and no new/recurrent infections should have occurred prior to the Baseline Visit.

Active skin infection requiring systemic antimicrobials at Baseline/Randomization (Visit 2).

Skin lesion(s) due to conditions other than AA that would interfere with the study specified assessments.

Prior treatment with apremilast, or participation in a clinical study involving apremilast.

Use of phototherapy (ie, UVB, UVA) or systemic immunosuppressive drugs (including, but not limited to, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine, Methotrexate, or tacrolimus), or oral preparations of herbal immunomodulatory medications within four weeks prior to Baseline/Randomization (Visit 2).

Use of interferon-γ within 12 weeks prior to Baseline/Randomization (Visit 2). Use of abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or tocilizumab within 12 weeks prior to Baseline/Randomization (Visit 2).

Use of oral janus kinase (JAK) inhibitors (e.g. tofacitinib, ruxolitinib) within 12 weeks prior to Baseline/Randomization (Visit 2).

Use of omalizumab, rituximab, ustekinumab, alefacept, briakinumab, or other therapeutic antibody products within 24 weeks prior to Baseline/Randomization (Visit 2).

Use of any investigational drug within four weeks or five PK or PD half lives (whichever is longer) prior to Baseline/Randomization (Visit 2).

Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other topical preparations with immunomodulatory properties within 2 weeks prior to Baseline/Randomization (Visit 2).

Prior history of suicide attempt at any time in the subject's lifetime prior to Baseline (Visit 2) or major psychiatric illness requiring hospitalization within 3 years prior to Baseline (Visit 2).

History of male or female pattern hair loss Ludwig stage III or Hamilton \> stage V.

Patients in whom the diagnosis of alopecia areata is in question, or subjects with scarring alopecia.