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

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

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.

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.

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