Clinical trial NCT03521687: Apremilast in the Treatment of Central Centrifugal Cicatricial Alopecia (CCCA)
Official title: An Open-label Pilot Study to Investigate the Efficacy of Apremilast in the Treatment of Central Centrifugal Cicatricial Alopecia (CCCA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Central Centrifugal Cicatricial Alopecia
Keywords: Central centrifugal cicatricial alopecia
open-label pilot study
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2018-05-11
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label study that will enroll 20 subjects with central centrifugal cicatricial alopecia. All subjects will receive apremilast.
Primary purpose: TREATMENT

Brief summary: This is a single-center, open-label clinical study to study the efficacy of apremilast in the treatment of mild to moderate central centrifugal cicatricial alopecia. The investigators hypothesize that the anti-inflammatory properties of apremilast may play a role in the decreasing scalp inflammation in patients with CCCA and may prevent further hair loss and potentially induce hair regrowth in patients with mild to moderate disease.

Detailed description: Central centrifugal cicatricial alopecia (CCCA) is a type of scarring alopecia commonly seen in women of African American descent. The etiology is not completely understood, but CCCA likely results from a combination of hair-grooming practices, a pro-inflammatory state within the hair follicles, and genetic factors. The management of CCCA remains a challenge as there are no published treatment guidelines. Current therapies aim to decrease inflammation in order to prevent further hair loss.

Apremilast, an oral phosphodiesterase-4 inhibitor, has been shown to be effective in the treatment of moderate to severe plaque psoriasis and psoriatic arthropathy. In vitro studies have demonstrated anti-inflammatory properties via inhibition of inflammatory mediators. Therefore, apremilast offers a possible therapeutic option for CCCA. This will be a single-center, open-label clinical study to determine the efficacy of apremilast in the treatment of mild to moderate central centrifugal cicatricial alopecia.

Eligibility criteria: Inclusion Criteria:

* Provide written, signed and dated informed consent prior to initiating any study-related activities
* Females of African ancestry \>18 years of age at the time of screening
* Clinical diagnosis of mild to moderate vertex-predominant CCCA as defined by CHLG stages 1B, 2B, 3B
* Punch biopsy at screening, or punch biopsy of the scalp within six months prior to screening visit, consistent with CCCA
* 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, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options.
* Must be in general good health as judged by the Investigator, based on medical history and physical examination. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions).

Exclusion Criteria:

* Systemic or intralesional treatment of CCCA for 4 weeks prior to baseline visit, including but not limited to corticosteroids (systemic, intralesional), oral tetracycline antibiotics, and oral anti-inflammatory medications
* Topical corticosteroid or calcineurin inhibitor treatment of CCCA for 2 weeks prior to baseline visit.
* Topical minoxidil for 4 weeks prior to baseline visit.
* Severe or end-stage CCCA with CHLG as defined as CHLG \>3
* CCCA with frontal accentuation pattern as defined as CHLG 1A to 5A.
* Diagnosis of other dermatologic diagnosis or condition that, in the opinion of the investigator, would interfere with diagnosis, examination, or treatment of the studied condition (i.e. lichen planopilaris, systemic lupus, cutaneous lupus) or would require treatment with systemic steroids, topical or intralesional steroids on the scalp, or systemic tetracycline antibiotic therapy during the duration of the study.
* Other than the disease under study, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease that is currently uncontrolled.
* 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 cervix with no evidence of recurrence within the previous 5 years.
* Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
* Use of systemic immunosuppressive drugs (including, but not limited to, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, or tacrolimus) within four weeks prior to Baseline/Randomization (Visit 2).
* Prior history of suicide attempt at any time in the subject's life time prior to screening or randomization, or major psychiatric illness requiring hospitalization within the last 3 years.
* Pregnant or breast feeding.
* Subjects not willing to implement the following suggested hair care practices and/or maintain the same or similar hair style for the duration of study: Shampoo hair every 7 days with a conditioning shampoo; Condition hair every 7 days with a deep or reconstructive conditioner; Towel-dry hair before exposing it to a dryer to minimize excessive heat; Comb hair daily with a wide-toothed comb; gently pass the comb through hair starting from the ends and working your way up to the roots; Avoid heavy pomades and hair oils to scalp; opt for silicone based products or light pomades to hair shafts; Limit use of styling gels; Limit traction-associated hair styles (e.g. tight braids, tight weaves, tight cornrows) as determined by investigator; Avoid chemical or thermal injury to scalp during hair styling process; Chemical relaxer treatments can be used as long as there is no associated scalp injury (i.e. tingling, burning, pain); Maintain the same hair style throughout the study i.e. weave or braids present at baseline must be maintained through the end of the study; weaves or braids may be redone during the study if needed, but should resemble the subject's hair style at baseline, if possible.
* Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamics half-lives, if known (whichever is longer).
* Prior treatment with apremilast
* History of allergy to any component of the IP
* Active substance abuse or a history of substance abuse within 6 months prior to Screening.

Primary outcomes:
measure: Mean Change in Physician Global Assessment of Improvement (PGA-I)
timeFrame: Week 0 and Week 24
Secondary outcomes:
measure: Mean Change in CCCA Investigator Global Severity Score (IGSS)
timeFrame: Week 0 and Week 24
measure: Mean Change in Central Hair Loss Grade (CHLG)
timeFrame: Week 0 and week 24
measure: Mean Change in Subject Visual Analog Scale (VAS) of Hair Loss Severity
timeFrame: Week 0 and Week 24
measure: Mean Change in Subject Global Assessment of Improvement
timeFrame: Week 0 and Week 24
measure: Change in Subject Rating of Symptom Severity Questionnaire (NRS)
timeFrame: Week 0 and Week 24
measure: Mean Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score
timeFrame: Week 0 and Week 24
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai West Dermatology
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Saakshi Khattri, MD
role: PRINCIPAL_INVESTIGATOR
References: