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

• Sponsor: Clinuvel Pharmaceuticals Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04525157
• Collaborator: (none)
• Enrollment: 21
• Arms: 3
• Actual Duration (Months): 24

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vitiligo	Drug: Afamelanotide; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• 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.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 (Participant, 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.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jun 6, 2014
• Actual Primary Completion Date: Feb 2, 2016
• Actual Study Completion Date: Jun 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afamelanotide and NB-UVB 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
Placebo Comparator: Placebo and NB-UVB 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
Experimental: Single-Arm, Open Label Group 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

Outcome Measures

Primary Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Clinuvel Pharmaceuticals Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clinuvel Pharmaceuticals Limited
• ClinicalTrials.gov Identifier: NCT04525157
• Other Study ID Numbers: CUV103
• First Posted: Aug 25, 2020
• Last Update Posted: May 21, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Vitiligo; Afamelanotide

Study Results

Participant Flow

Recruitment Details	18 participants were enrolled in the Arm Afamelanotide and NB-UVB (pooled analysis)

Arm/Group Title	Afamelanotide and NB-UVB (Pooled Analysis)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	18
COMPLETED	15
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Afamelanotide and NB-UVB (Pooled Analysis)
Arm/Group Description	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.
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 22.2%
Male	14 77.8%

Outcome Measures

1. Primary Outcome

Title	Change in Pigmentation (Total and Individual Body Parts) Using the Vitiligo Area Scoring Index (VASI)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Afamelanotide and NB-UVB (Pooled Analysis)
Arm/Group Description	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.
Measure Participants	15
Total Day 28	0.00
Head and Neck Day 28	0.00
Hands Day 28	0.00
Upper Extremities Day 28	0.00
Trunk Day 28	0.00
Lower Extremities Day 28	0.00
Feet Day 28	0.00
Total Day 56	-0.05
Head and Neck Day 56	0.00
Hands Day 56	0.00
Upper Extremities Day 56	0.00
Trunk Day 56	0.00
Lower Extremities Day 56	0.00
Feet Day 56	0.00
Total Day 84	-0.70
Head and neck Day 84	0.00
Hands Day 84	0.00
Upper Extremities Day 84	0.00
Trunk Day 84	0.00
Lower Extremities Day 84	0.00
Feet Day 84	0.00
Total Day 112	-1.13
Head and Neck Day 112	-0.10
Hands Day 112	0.00
Upper Extremities Day 112	0.00
Trunk Day 112	-0.13
Lower Extremities Day 112	0.00
Feet Day 112	0.00
Total Day 140	-2.56
Head and Neck Day 140	-0.11
Hands Day 140	0.00
Upper Extremities Day 140	-0.50
Trunk Day 140	-0.50
Lower Extremities Day 140	-0.50
Feet Day 140	0.00
Total Day 168	-2.86
Head and Neck Day 168	-0.13
Hands Day 168	0.00
Upper Extremities Day 168	-0.50
Trunk Day 168	-1.00
Lower Extremities Day 168	-0.75
Feet Day 168	0.00
Total Day 196	-3.70
Head and Neck Day 196	-0.13
Hands Day 196	0.00
Upper Extremities Day 196	-1.00
Trunk Day 196	-1.13
Lower Extremities Day 196	-0.60
Feet Day 196	0.00

Adverse Events

Arm/Group Title	Afamelanotide and NB-UVB (Pooled Analysis)
Arm/Group Description	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.
All Cause Mortality
	Afamelanotide and NB-UVB (Pooled Analysis)
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Serious Adverse Events
	Afamelanotide and NB-UVB (Pooled Analysis)
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Other (Not Including Serious) Adverse Events
	Afamelanotide and NB-UVB (Pooled Analysis)
	Affected / at Risk (%)	# Events
Total	4/18 (22.2%)
General disorders
Fatigue	1/18 (5.6%)
Investigations
Glomerular filtration rate decreased	1/18 (5.6%)
Urinary casts	1/18 (5.6%)
Nervous system disorders
Lethargy	1/18 (5.6%)
Skin and subcutaneous tissue disorders
Nail pigmentation	2/18 (11.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.