Central Centrifugal Cicatricial Alopecia, Lichen Planopilaris
Conditions
Brief summary
This study evaluates the safety, tolerability, and biomarker effects of twice-daily topical delgocitinib 2% cream in adults with lichen planopilaris (LPP) or central centrifugal cicatricial alopecia (CCCA) over a 48-week treatment period. Approximately 30 participants will be enrolled: 15 CCCA and 15 LPP. The study will take place at the Icahn School of Medicine at Mount Sinai (ISMMS).
Interventions
DRUGDelgocitinib
twice-daily topical 2% cream
Sponsors
Icahn School of Medicine at Mount Sinai
LEO Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants of any gender, age 18 years or older, at the time of informed consent at Screening. * Participants who are willing and able to adhere to the study visit schedule and comply with protocol requirements. * Participant self-reports a history of at least 6 months of CA (LPP or CCCA). Diagnosis will be made clinically (according to the LPPAI10, and/or CHLG11) and/or histopathologically. * Participants who are females of childbearing potential must have a negative urine pregnancy test at screening and must be practicing an adequate and medically acceptable method of birth control for at least 30 days prior to Day 0 and at least 28 days after the last dose of study drug. Acceptable methods of birth control include intrauterine device (IUD) oral, transdermal, implanted or injected hormonal contraceptives (must have been initiated at least 1 month before entering the study); tubal ligation; abstinence; barrier methods with spermicide. If not of child-bearing potential, Participants must have a sterile or vasectomized partner; have had a hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in a menopausal state for at least a year. * Participant is judged to be in otherwise good overall health following a detailed medical and medication history, physical examination, and laboratory testing.
Exclusion criteria
* Participants of hair loss is indeterminable and/or they have concomitant causes of alopecia, such pregnancy-related, drug-induced, telogen effluvium, or advanced androgenetic alopecia. * Participant has a history of CA for ≥ 4 years since the disease onset, severe fibrosing disease, or very rapid hair loss at screening. * Participant has a history of moderate to severe keloids on the scalp, as determined by clinical examination at screening. * Other scalp disease that may impact assessment (e.g., scalp psoriasis, dermatitis, etc.). * Participant is pregnant or breastfeeding. * Participation in other studies involving investigational drug(s) within 4 weeks or within 5 half-lives (if known), whichever is longer, prior to study entry and/or during study participation (de novo patients only). * Active systemic diseases that may cause hair loss (e.g., systemic lupus erythematosus, thyroiditis, systemic sclerosis, etc.). * Any Psychiatric condition in the opinion of the investigator precludes participation in the study. * Current or recent history of clinically significant severe, progressive, or uncontrolled renal (including but not limited to active renal disease or recent kidney stones), hepatic, hematological, gastrointestinal, metabolic, endocrine (particularly thyroid disease which can be associated with hair loss), pulmonary, cardiovascular, psychiatric, immunologic/rheumatologic or neurologic disease; or have any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or interfere with the interpretation of study results; or in the opinion of the investigator, the participant is inappropriate for entry into this study, or unwilling/unable to comply with STUDY PROCEDURES. * History of thromboembolic events including DVT and PE or history of inherited coagulopathies. * Any present malignancies or history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. * History of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease. * History of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 0. * Active acute or chronic infection requiring treatment with oral antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 0 or superficial skin infection within 1 week prior to Baseline. * Considered in imminent need for surgery or with elective surgery scheduled to occur during the study. * Have an active history of alcohol or substance abuse within 1 year prior to Day 0. * Participant has any uncertain or clinically significant laboratory abnormalities that may affect interpretation of study data or endpoints, at determined by the PI. * History of adverse systemic or allergic reactions to components of study drug. * Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, within 8 weeks prior to baseline visit. * Use of other non-biologic systemic agent for CA, including, 5α-reductase inhibitors, hydroxychloroquine, or retinoids, within 4 weeks prior to baseline visit. * Use of an intralesional corticosteroids or oral JAK inhibitor (tofacitinib, ruxolitinib, or any JAK1/TYK2 product) within 4 weeks prior to the baseline visit. * Participant has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus or cyclosporine within 1 week before the baseline visit. * Participant has been previously treated with biological drugs in the last 12 weeks for other indications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in IFNγ in CA scalp in delgocitinib-treated patients | Baseline to Week 36 | Changes in Th1 markers in CA scalp from baseline to week 36 in delgocitinib-treated patients |
| Changes in CCL5 in CA scalp in delgocitinib-treated patients | Baseline to Week 36 | Changes in Th1 markers in CA scalp from baseline to week 36 in delgocitinib-treated patients |
| Changes CXCL9 markers in CA scalp in delgocitinib-treated patients | Baseline to Week 36 | Changes in Th1 markers in CA scalp from baseline to week 36 in delgocitinib-treated patients |
| Changes in CXCL10 in CA scalp in delgocitinib-treated patients | Baseline to Week 36 | Changes in Th1 markers in CA scalp from baseline to week 36 in delgocitinib-treated patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in IFNγ in CA scalp in delgocitinib-treated patients | Week 36 to Week 48 | Changes in Th1 markers in CA scalp from baseline to week 48 and from week 36 to week 48 |
| Changes in CCL5 in CA scalp in delgocitinib-treated patients | Week 36 to Week 48 | Changes in Th1 markers in CA scalp from baseline to week 48 and from week 36 to week 48 |
| Changes in CXCL9 in CA scalp in delgocitinib-treated patients | Week 36 to Week 48 | Changes in Th1 markers in CA scalp from baseline to week 48 and from week 36 to week 48 |
| Changes in Th1 markersCXCL10in CA scalp in delgocitinib-treated patients | Week 36 to Week 48 | Changes in Th1 markers in CA scalp from baseline to week 48 and from week 36 to week 48 |
| Changes in TGFB1/2 | Baseline to Week 36; Baseline to Week 48 | Changes in biomarkers of fibrosis at weeks 36 and at weeks 48 |
| Changes in vimentin | Baseline to Week 36; Baseline to Week 48 | Changes in biomarkers of fibrosis at weeks 36 and at weeks 48 |
| Changes in fibronectin | Baseline to Week 36; Baseline to Week 48 | Changes in biomarkers of fibrosis at weeks 36 and at weeks 48 |
| Changes in CTGF | Baseline to Week 36; Baseline to Week 48 | Changes in biomarkers of fibrosis at weeks 36 and at weeks 48 |
| Change in Central Hair Loss Grade (CHLG) | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | The Central Hair Loss Grade is a clinical measure of severity that uses a 6 points scale (0 no central scalp hair loss, 1 - minimal central scalp hair loss, 2 - clinically evident central scalp hair loss, 3-5 advanced central scalp hair loss) |
| Change in Lichen Planopilaris Activity Index (LPPAI) | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | The Lichen Planopilaris Activity Index is a standardized validated quantitative measure of disease activity. LPPAI score (0-10) is calculated as follows: (pruritus + pain + burning)/3 + (scalp erythema + perifollicular erythema + perifollicular scale)/3 + 2.5 (pull test) + 1.5 (spreading/2). Symptoms and signs are graded on a 4-point scale with 0 = absent, 1 = mild, 2 = moderate, and 3 =severe. Clinical progression and a positive hair pull test are graded 1=yes; 0=no. |
| Molecular cutaneous phenotype of CCCA and LPP by molecular studies in scalp tissues acquired via biopsies | Baseline to Week 48; Week 24 to Week 48 | An Analysis of Covariance will be used to analyze the changes induced by Delgocitinib in CCL5 (a surrogate for IFNγ activity) and biomarkers of fibrosis expression in CA scalp from baseline to week 48 and from week 24 to week 48. |
| Change in Dermatology Quality of Life Index (DLQI) | Baseline to Week 24, Baseline to Week 36, Baseline to Week 48 | Full score on scale from 0 to 30, with higher indicating higher impact on quality of life. |
| Change in hair count per cm2 | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in number of hairs present in a 1cm2 area |
| Change in sum of hair width per cm2 | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in total hair diameter in a 1cm2 area |
| Change in terminal:vellus ratio | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in the ratio of thick pigmented long hair to fine-barely visible hairs |
| Change in average hairs per follicular unit | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in average number of hairs growing out of each pore |
| Change in average hair width | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in average width of each individual hair |
| Change in follicular units per cm2 | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in hair density in a 1cm2 area |
| Change in inter-follicular mean distance | Baseline to Week 24; Baseline to Week 36; Baseline to Week 48 | Change in average gap between hairs |
| Change in Peak Pruritus Numerical Rating Scale (PP-NRS) | Baseline to Week 24, Baseline to Week 36, Baseline to Week 48 | The score ranges from 0 - 10 with 0 representing no itch and 10 representing worse possible itch. |
Countries
United States
Contacts
CONTACTSharlene Martin, MPH
PRINCIPAL_INVESTIGATORBenjamin Ungar, MD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed