Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Phototherapy in the Treatment of Nonsegmental Vitiligo (NSV)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of afamelanotide, when combined with narrowband ultraviolet B (NB-UVB) phototherapy, in patients with nonsegmental vitiligo. Afamelanotide is expected to increase the rate of the repigmentation induced by NB-UVB, leading to a reduced frequency and dose of NB-UVB.

Detailed Description
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Vitiligo is the most common depigmentation disorder. A commonly used treatment is phototherapy with narrow-band ultraviolet B irradiation (NB-UVB). Further therapeutic approaches are desired and currently being evaluated. The investigational product, afamelanotide, is a synthetic analogue of the human alpha melanocyte stimulating hormone (alpha-MSH). Afamelanotide activates melanin in skin, with the controlled-release injectable implant formulation having an affect across the total body surface area (pandermally). Earlier studies in vitiligo patients showed afamelanotide, in combination with NB-UVB, could induce faster and deeper repigmentation in patients compared to NB-UVB alone.

Official Title
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A Two-Arm, Randomized, Double-Blind, Phase IIb Study to Compare the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants Plus Narrow-Band Ultraviolet B (NB-UVB) Light Source With Narrow-Band Ultraviolet B (NB-UVB) Light Source in the Treatment of Nonsegmental Vitiligo AND A Single-Arm, Open Label, Phase IIb Study to Evaluate the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants Plus Narrow-Band Ultraviolet B (NB-UVB) Light Source in the Treatment of Nonsegmental Vitiligo

Conditions
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Vitiligo

Intervention / Treatment
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* Drug: Afamelanotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: for double-blind phase: Male and female subjects with a confirmed diagnosis of nonsegmental vitiligo with 15% to 50% of total body surface involvement for open label phase: Male and female subjects with a confirmed diagnosis of nonsegmental vitiligo with 10% to 50% of total body surface involvement Vitiligo involving the head and neck Stable or slowly progressive vitiligo over a 3-month period Aged 21 years or more Willing and able to comply with the conditions specified in this protocol and study procedures, in the opinion of the Investigator Provided written Informed Consent prior to the performance of any study-specific procedure Exclusion Criteria: Extensive leukotrichia, in the opinion of the Investigator Previous treatment with NB-UVB light or other light source within 6 weeks prior to the Screening Visit Patient not responsive to previous NB-UVB light treatment, defined as a patient who had undergone at least 20 NB-UVB sessions with no or minimal clinically relevant pigmentary response, in the opinion of the Investigator Previous topical treatment for vitiligo, including topical immunomodulators (e.g. corticosteroids, calcineurin inhibitors), within 4 weeks prior to the Screening Visit Allergy to afamelanotide or the polymer contained in the implant or to lignocaine/lidocaine or other local anaesthetic to be used during the administration of the implant History of photosensitivity disorders Claustrophobia Any active and/or unstable autoimmune disease judged to be clinically significant by the Investigator Any current skin disease that may have interfered with the study evaluation Female who was pregnant (confirmed by positive β-human chorionic gonadotropin (HCG) pregnancy test) or lactating Female of child-bearing potential (pre-menopausal, not surgically sterile) not using adequate contraceptive measures (i.e. oral contraceptives or diaphragm plus spermicide or intrauterine device) during the treatment phase (7 months) and for a period of three months thereafter - except if abstinence from intercourse was practiced Sexually active man with a partner of child-bearing potential (pre-menopausal, not surgically sterile) who was not using adequate contraceptive measures, as described above Participated in a clinical trial for an investigational agent within 30 days prior to the Screening Visit

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A Two-Arm, Randomized, Double-Blind Study and a Single-Arm, Open Label, Phase IIb Study to Evaluate the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants plus Narrow-Band Ultraviolet B (NBUVB) Light Source in the Treatment of Nonsegmental Vitiligo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afamelanotide and NB-UVB<br>Participants received Afamelanotide implants (Days 28, 56, 112, 140, and 168) and NB-UVB light (twice weekly for 7 months from Day 0). | Drug: Afamelanotide<br> <br> |
| Placebo Comparator: Placebo and NB-UVB<br>Participants received Placebo implants (Days 28, 56, 112, 140, and 168) and NB-UVB light (twice weekly for 7 months from Day 0). | Drug: Placebo<br> <br> |
| Experimental: Single-Arm, Open Label Group<br>The study design was modified into a single-arm, open label study with only one treatment group receiving afamelanotide implants plus NB-UVB light. Participants received Afamelanotide implants (Days 28, 56, 112, 140, and 168) and NB-UVB light (twice weekly for 7 months from Day 0). | Drug: Afamelanotide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | A decrease in VASI over time indicates a reduction of the body surface area affected by vitiligo and/ or a reduction in the body sites' degree of depigmentation (possible range 1-100) | From Day 0 to Day 196 |