Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP)

Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP)-Related Skin Disease.

The primary objective is to evaluate the impact of afamelanotide on the severity of skin disease in patients with Variegate Porphyria (VP). The secondary objectives are to evaluate the safety and tolerability of afamelanotide in patients with VP and evaluate the impact of afamelanotide on the quality of life of patients with VP.

Study Overview

• Status: Completed
• Conditions: Variegate Porphyria
• Intervention / Treatment: Drug: Afamelanotide 16 MG

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • CLINUVEL investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients with confirmed diagnosis of VP.
• Patients with VP-related skin symptoms.
• Aged 18-70 years.

Exclusion Criteria:

• Allergy to afamelanotide or polymer or to local anaesthetic to be used if applicable.
• Had two or more acute attacks of hepatic porphyria, as defined by the occurrence or acute porphyric symptoms within 12 months prior to the Screening period.
• Individual history of malignant or premalignant skin lesions.
• Individual or family history of melanoma.
• Presence of severe hepatic disease.
• Renal impairment.
• Female who is pregnant or lactating.
• Females of child-bearing potential not using adequate contraceptive or a life-style excluding pregnancy.
• Sexually active man with a partner of child-bearing potential not using adequate contraceptive measures.
• Use of any other prior and concomitant therapy which may interfere with the objective of the study, within 30 days prior to the Screening period.
• Participation in a clinical trial within 30 days prior to the Screening period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afamelanotide	Drug: Afamelanotide 16 MG; Eligible patients will receive one dose of afamelanotide 16mg every 28 days (up to six doses), as a controlled-release formulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in Disease Severity in Patients With VP as Measured by CGIC.	The higher the score, the less severe the disease. Scale ranges from +3 to -3.	From baseline to Day 168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in Disease Severity in Patients With VP as Measured by 11-point VAS IGA.	A lower score indicates a reduced severity of the disease.Scale ranges from 0 to 10.	Median change from baseline to Day 168.
The Change in Disease Severity in Patients With VP as Measured by 5-point IGA.	A lower score indicates a reduced severity of the disease. Scale ranges from 0 to 4.	Median change from baseline to Day 168
The Change in Disease Severity in Patients With VP as Measured by PGIC.	The higher the score, the less severe the disease. Score ranges from +3 to -3.	Median change from baseline to Day 168
The Change in Disease Severity in Patients With VP as Measured by PGA Using VAS.	A lower score indicates a reduced severity of the disease. Scale ranges from 0 to 10.	Median change from baseline to Day 168
The Change in Number of New Skin Lesions Formed.	A lower number indicates a reduced severity of the disease.	Median change from baseline to Day 168.
The Change in the Quality of Life in Patients With VP as Measured by WPAI:GH.	Higher score indicates greater impairment and less productivity. Score is percentage impairment.	Median of change from baseline to Day 168
The Change in the Quality of Life in Patients With VP as Measured by VP-derived QOLEB.	Higher scores represent worse health-related quality of life. Scale ranges from 0 to 45.	From baseline to Day 168
The Change in the Quality of Life in Patients With VP as Measured by VP QoL.	"Quality of life measured by the number of responses of "much better than a year ago" to the question "How would you judge the condition of your skin of your face and hands today, in comparison to the situation last year (12 months ago)?"	Assessed at baseline and Day 168 to reflect retrospective changes over the previous 12 months.
The Change in Outdoor Light Exposure Over Time (Daily Diary)	Daily diaries recording outdoor light exposure.	From baseline to Day 168.

Collaborators and Investigators

• Sponsor: Clinuvel Pharmaceuticals Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Actual): December 28, 2023
• Study Completion (Actual): December 28, 2023

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Skin Diseases; Skin Diseases, Genetic; Porphyrias, Hepatic; Porphyria, Erythropoietic; Porphyrias; Porphyria, Variegate; Dermatologic Agents; Afamelanotide
• Other Study ID Numbers: CUV040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes