Evaluation of Afamelanotide's Effect on UV-Induced DNA Damage and Repair in Healthy Volunteers

The primary objective of this study is to evaluate the impact of **afamelanotide** in aqueous solution on total ultraviolet radiation (UVR)-induced direct DNA damage in healthy human skin. This is clinically relevant as it aims to understand the protective effects of afamelanotide, a synthetic hormone analogue, against UVR-induced DNA damage, which is a critical factor in skin cancer prevention and skin health maintenance. The study involves the administration of afamelanotide via subcutaneous injection, with a maximum daily dose of 0.08 mg/kg and a total dose of 0.32 mg/kg over a treatment period of four weeks. There are no secondary objectives listed for this study.

The clinical trial involves **healthy volunteers** with a focus on evaluating the impact of afamelanotide in aqueous solution on total UVR-induced direct DNA damage in healthy human skin. The study population consists of adult males and females aged between 18 and 45 years, with a **Body Mass Index (BMI)** ranging from 18 to 30 kg/m². Participants are required to have a heart rate between 50 and 90 bpm, blood pressure below 120/80 mm Hg and above 90/60 mm Hg, and normal renal and hepatic function as determined through laboratory testing. They must be free of significant abnormal findings as determined during the screening procedure by medical history, laboratory testing, and vital signs. The trial excludes individuals with a history of drug abuse, both licit and illicit, as assessed through medical history review and a urine drug screening test. Participants must agree not to use any non-prescribed medications and be willing to take precautions to prevent pregnancy with their partner. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the impact of **afamelanotide** in aqueous solution on ultraviolet radiation (UVR)-induced DNA damage and DNA repair capacity in healthy volunteers. This study is a randomized, double-blind, controlled trial, categorized as a Phase IV trial. The trial will involve healthy adult males and females aged between 18 and 45 years, with specific inclusion criteria such as a heart rate between 50 and 90 bpm, blood pressure below 120/80 mm Hg and above 90/60 mm Hg, and normal renal and hepatic function. Participants must also have a Body Mass Index (BMI) between 18 and 30 kg/m² and be free of significant abnormal findings as determined during the screening procedure.

The trial is expected to commence recruitment on May 13, 2024, and conclude by December 6, 2024. The study will involve a series of visits, beginning with an inclusion (screening) visit to assess eligibility based on the inclusion criteria. Participants will then undergo a series of follow-up visits where they will receive the investigational product, **PRENUMBRA**, administered via subcutaneous injection. The primary endpoint of the study is to measure the changes in UV photoproducts from pre to post-afamelanotide in UVR-exposed skin and in non-irradiated skin. The maximum treatment period is set at four weeks, with a maximum daily dose of 0.08 mg/kg and a total dose not exceeding 0.32 mg/kg.

The expected length of participant involvement is approximately four weeks, with conditions for early termination including non-compliance with the study protocol, adverse events, or withdrawal of consent. The end-of-study visit will involve final assessments to evaluate the primary endpoint and ensure participant safety. The trial is conducted under the sponsorship of CLINUVEL PHARMACEUTICALS LTD, with the investigational product being a synthetic hormone analogue. Participants are required to agree not to use any non-prescribed medications and to take precautions to prevent pregnancy during the study period.

The clinical trial involves the administration of the experimental medication **afamelanotide**, marketed under the name **PRENUMBRA**. This medication is provided in the form of a **solution for injection**. The active substance, afamelanotide, is a synthetic hormone analogue classified as a protein of other origin. The pharmaceutical form is specifically designed for **subcutaneous injection**. The dosing regimen for afamelanotide is set at a maximum daily dose of 0.08 mg/kg, with a total maximum dose of 0.32 mg/kg over the treatment period. The maximum treatment duration is four weeks. The administration of the drug is monitored to ensure compliance with the dosing schedule.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the impact of afamelanotide on ultraviolet radiation-induced DNA damage and DNA repair capacity in healthy volunteers. Participant compliance with the dosing schedule is closely monitored to ensure the integrity of the trial results. The trial is conducted under the sponsorship of CLINUVEL PHARMACEUTICALS LTD, with the medication being authorized for use in this specific clinical investigation.

Efficacy in this clinical trial will be assessed by evaluating the impact of **afamelanotide** on ultraviolet radiation (UVR)-induced DNA damage in healthy human skin. The primary endpoint for efficacy evaluation is the change in UV photoproducts from pre to post administration of afamelanotide in both UVR-exposed and non-irradiated skin. This assessment will provide insights into the compound's effect on DNA repair capacity and its potential protective role against UVR-induced damage. The trial is designed to measure these changes using appropriate laboratory tests and methodologies, ensuring accurate and reliable data collection. The study will follow a structured schedule to collect and analyze these parameters, although specific timepoints for these assessments are not detailed in the provided information. The trial is categorized as a Phase II study, focusing on the mechanistic understanding of afamelanotide's effects in a controlled setting.