Vitiligo
Conditions
Brief summary
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
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.
Interventions
DRUGAfamelanotide
DRUGPlacebo
Sponsors
Clinuvel Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
In the first half of the study, the Participant and Investigator are masked. In the second half of the study, the study is single arm, Open Label Study.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | From Day 0 to Day 196 | 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) |
Participant flow
Recruitment details
18 participants were enrolled in the Arm Afamelanotide and NB-UVB (pooled analysis)
Participants by arm
| Arm | Count |
|---|---|
| Afamelanotide and NB-UVB (Pooled Analysis) The study design was modified from a randomised controlled (Afamelanotide plus NB-UVB versus placebo plus NB-UVB) to an open label study (afamelanotide plus NB-UVB). A pooled analysis of all patients who received afamelanotide plus NB-UVB was undertaken and the results are presented. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Afamelanotide and NB-UVB (Pooled Analysis) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 4 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
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)
Time frame: From Day 0 to Day 196
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and Neck Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 28 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 56 | -0.05 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and Neck Day 56 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 56 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 56 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 56 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 56 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 56 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 84 | -0.70 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and neck Day 84 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 84 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 84 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 84 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 168 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 196 | -3.70 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and Neck Day 196 | -0.13 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 196 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 196 | -1.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 196 | -1.13 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 196 | -0.60 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 196 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 84 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 84 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 112 | -1.13 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and Neck Day 112 | -0.10 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 112 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 112 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 112 | -0.13 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 112 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 112 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 140 | -2.56 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and Neck Day 140 | -0.11 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 140 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 140 | -0.50 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 140 | -0.50 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 140 | -0.50 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Feet Day 140 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Total Day 168 | -2.86 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Head and Neck Day 168 | -0.13 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Hands Day 168 | 0.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Upper Extremities Day 168 | -0.50 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Trunk Day 168 | -1.00 Change in VASI score from baseline |
| Afamelanotide and NB-UVB (Pooled Analysis) | Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI) | Lower Extremities Day 168 | -0.75 Change in VASI score from baseline |