A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum C and V

Study Overview
=================
Brief Summary
-----------------
The CUV152 study will evaluate the safety of afamelanotide in XP-C and XP-V patients, as well as the drug's ability to assist reparative processes following ultraviolet (UV) provoked DNA damage of the skin. It will assess whether SCENESSE® increases the amount of UV light needed to cause DNA damage of skin cells, as well as the extent of skin repair before and after treatment.

Official Title
-----------------
A Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety and Efficacy of Subcutaneous Implants of Afamelanotide in Patients With Xeroderma Pigmentosum C and V (XPC and XPV)

Conditions
-----------------
Xeroderma Pigmentosum

Intervention / Treatment
-----------------
* Drug: Afamelanotide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patient with a molecular-genetically confirmed diagnosis of XP-C or XP-V; Aged 18-75 years. Exclusion Criteria: Known allergy to afamelanotide or the polymer contained in the implant; Presence of severe hepatic disease or hepatic impairment; Renal impairment; Any other medical condition which may interfere with the study protocol; Existing melanoma; Female who is pregnant or lactating; Females of child-bearing potential (pre-menopausal, not surgically sterile) not using adequate contraceptive measures; Sexually active man with a partner of child-bearing potential who is not using adequate contraceptive measures; Use of any other prior and concomitant therapy which may interfere with the objective of the study; Participation in a clinical trial for an investigational agent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afamelanotide<br> | Drug: Afamelanotide<br>* Patients will receive afamelanotide every two weeks for twelve weeks and undergo a follow up visit 6 months later.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in minimal erythema dose (MED) in patients with XP-C. | MED is the lowest dose of UV light that causes reddening of the skin. | From baseline to day 76. | 
| Change in MED in patients with XP-V. | MED is the lowest dose of UV light that causes reddening of the skin. | From baseline to day 76. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in UV-induced DNA damage, as assessed by quantification of UV photoproduct levels in patients with XP-C. | Analysis of UV photoproducts from skin samples. | From baseline to day 76. | 
| Changes in UV-induced DNA damage repair capacity, as assessed by quantification of DNA repair mechanisms in patients with XP-C. | Analysis of DNA repair mechanisms from skin samples. | From baseline to day 76. | 
| Changes in UV-induced DNA damage, as assessed by quantification of UV photoproduct levels in patients with XP-V. | Analysis of UV photoproducts from skin samples. | From baseline to day 76. | 
| Changes in UV-induced DNA damage repair capacity, as assessed by quantification of DNA repair mechanisms in patients with XP-V. | Analysis of DNA repair mechanisms from skin samples. | From baseline to day 76. | 
| Change in skin disease severity in patients with XP-C (A). | The higher the score, the more severe the disease. | From baseline to day 76. | 
| Change in skin disease severity in patients with XP-V (A) | The higher the score, the more severe the disease. | From baseline to day 76. | 
| Change in skin disease severity in patients with XP-C (B). | The higher the score, the more severe the disease. | From baseline to day 76. | 
| Change in skin disease severity in patients with XP-V (B). | The higher the score, the more severe the disease. | From baseline to day 76. | 
| Change in skin disease severity in patients with XP-C (C). | The higher the score, the more severe the disease. | From baseline to day 76. | 
| Change in skin disease severity in patients with XP-V (C). | The higher the score, the more severe the disease. | From baseline to day 76. | 
| Change in quality of life assessed by a disease specific tool (A) in patients with XP-C. | Higher scores represent worse health-related quality of life. | From baseline to day 76. | 
| Change in quality of life assessed by a disease specific tool (A) in patients with XP-V. | Higher scores represent worse health-related quality of life. | From baseline to day 76. | 
| Change in quality of life assessed by a validated global quality of life tool (B) in patients with XP-C. | Score calculated in impairment percentages, with higher numbers indicating greater impaired quality of life. | From baseline to day 76. | 
| Change in quality of life assessed by a validated global quality of life tool (B) in patients with XP-V. | Score calculated in impairment percentages, with higher numbers indicating greater impaired quality of life. | From baseline to day 76. |