Combined Therapy With Narrow-Band Ultraviolet B Phototherapy and Apremilast for the Treatment of Vitiligo

NCT03123016 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: GCO 16-1261
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Vitiligo is a common acquired disorder of pigmentation affecting 0.5% to 1% of the world population. Sharply demarcated patches of depigmentation, which can affect all ethnicities, and can lead to cosmetic disfiguration and psychosocial distress, characterize the disease. The etiology of vitiligo remains unknown. Various mechanisms have been proposed, such as autoimmunity, self-destruction, biochemical, genetic, neural, oxidative stress, and an imbalance of epidermal cytokines leading to inflammation and selective loss of epidermal melanocytes. Currently, the most popular theory is autoimmunity. Previous studies noted that around 25-30% of patients have at least one other autoimmune disease, such as autoimmune thyroid disease, Addison's disease, pernicious anemia, and alopecia areata. Currently, NB-UVB phototherapy is the most widely used therapeutic option for vitiligo affecting more than 10-20% of the skin surface, as it is generally considered to be a safe initial treatment. Potential side effects include phototoxic reaction, thickening of the skin and koebnerization. NB-UVB is a band of UV radiation with a wavelength of 311-313 nm. UVB induces mitogenesis and migration in melanocytes mediated by several factors such as IL-1, TNF alpha, and leukotriene C4. UV radiation produces increased number and activity of melanocytes, increased melanin density, elongation and branching of dendrites, with increased transfer of more heavily melanized melanosomes to keratinocytes, seen clinically as increased pigmentation. Apremilast is an oral small molecule phosphodiesterase-4 (PDE4) inhibitor that has been shown to regulate inflammatory mediators. Apremilast enters cells by passive diffusion and, once intracellular, binds PDE4. PDE-4, the dominant phosphodiesterase expressed in immune cells, degrades cyclic AMP (cAMP) into AMP. PDE4 inhibition thereby elevates intracellular cAMP, which can down-regulate the inflammatory responses such as TNF-α, IFN-γ, interleukins (IL) 2, 12 and 23 through mechanisms such as partially inhibiting expression of inflammatory cytokines and increasing expression of anti-inflammatory mediators such as IL2 and IL10. The hypothesis is that apremilast will shut down the inflammatory insult in vitiligo and NB-UVB phototherapy will then be able to regenerate melanocytes and their activity. By examination of skin biopsies taken pre- and post-therapy, the study team aims to assess changes in immune and cellular markers in affected skin.

Conditions

Vitiligo

Keywords

Vitiligo

Outcome Measures

Primary Outcomes (1)

• Change in proportion of responders to treatment from Week 16 to Week 32

  The proportion of responders to apremilast plus concomitant NB-UVB at week 32 compared to the proportion of responders to NB-UVB phototherapy at week 16.

  Week 16 and Week 32

Secondary Outcomes (6)

• Body Surface Area (BSA)

  Week 32 and Week 48

• VASI score - Vitiligo Area and Severity Index (VASI)

  Week 32 and Week 48

• VETF score - Vitiligo European Task Force (VETF) score

  Up to 64 weeks

• Dermatology Life Quality Index

  Up to 64 weeks

• Visual Analogue Scale (VAS)

  Up to 64 weeks

Study Arms (1)

Vitiligo with Apremilast and NB-UVB phototherapy

EXPERIMENTAL

Each participant will be compared with one side of the body to the other side

Drug: Apremilast; Procedure: NB-UVB phototherapy

Interventions

Apremilast DRUG

Apremilast 30 mg orally, twice daily. (oral tablet)

Vitiligo with Apremilast and NB-UVB phototherapy

NB-UVB phototherapy PROCEDURE

treatment with narrowband UVB two to three times weekly to one half of their body for a total of 16 weeks

Vitiligo with Apremilast and NB-UVB phototherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, ≥ 18 years of age at the time of signing the informed consent document.
• Must be in general good health (except vitiligo) as judged by the Investigator, based on medical history, physical examination, clinical laboratories, and urinalysis. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions).
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• Subjects must be clinically diagnosed by the investigator to have at least 20% body surface area involvement of generalized type vitiligo.
• Fitzpatrick skin phototypes IV, V, and VI.
• 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, 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

You may not qualify if:

• 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 \[CVID\]). 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).

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Celgene: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Vitiligo

Interventions

apremilast

Condition Hierarchy (Ancestors)

Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Mark Lebwohl, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and System Chair

Model Details: Enrolled subjects will be randomized to treatment with narrowband UVB two to three times weekly to one half of their body for a total of 16 weeks, while the contralateral side of the body is covered by a special garment to prevent any UVB treatment

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 21, 2017
• Study Start: April 14, 2017
• Primary Completion: August 5, 2019
• Study Completion: August 5, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)