NCT02716714

Clinical Trial of Ingenol Mebutate Gel 0.015% & 0.05% in Actinic Keratosis

A Multi-center, OPen, InvEstigator Initiated Phase IV Clinical TRial to Evaluate the Efficacy and SaFety of Ingenol Mebutate Gel 0.015% on Face and Scalp & 0.05% on Trunk and Extremities in KorEan Patient With ACtinic KeraTosis (PERFECT)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 77 (actual)
• Sponsor: Korea University · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

This study evaluate the efficacy and safety of ingenol mebutate gel 0.015% on face and scalp \& 0.05% on trunk and extremities in Korean patient with actinic keratosis.

Detailed description

The mechanism of action of ingenol mebutate for actinic keratosis(AK) treatment involves a rapid induction of necrosis followed by neutrophil-mediated, antibody-dependent cellular cytotoxicity (ADCC) of residual lesion. As the ingenol mebutate infiltrates the cell membrane, it increases intracellular Ca2+ concentration which leads to mitochondrial swelling and disruption of mitochondrial membrane within hours. The release of intra-mitochondrial Ca2+ into the cytoplasm leads to depletion of adenosine triphosphate (ATP) and a rapid induction of cell death by necrosis. This process occurs within 1 hour of application, which explains why the treatment period requires only 2 or 3 days of treatment. As the next phase, the cellular necrosis is accompanied by a robust inflammatory response through the release of proinflammatory cytokines from skin cells and tumor cells undergoing necrosis. The release of these proinflammatory cytokines into the dysplastic cells mediates the process of neutrophil recruitment through paracrine signaling and activation of endothelial cells. Here, the neutrophil mediated ADCC occurs, where activated neutrophils attach to the fragment, crystallized (Fc) parts of antibodies of dysplastic cells and destroys the residual dysplastic epidermal cells. In this way, the ingenol mebutate eradicates any residual tumor cells and prevents recurrence of actinic keratosis.As described above, the rapid effect and dual mechanism of action of ingenol mebutate gel allows not only a short-course therapy (2 or 3 days of application) for the elimination of actinic keratosis but also, the benefit for eradication of any residual lesions preventing the recurrence and the progression of AK into squamous cell carcinoma (SCC).

Conditions

• Actinic Keratosis

Interventions

Type	Name	Description
DRUG	ingenol mebutate gel 0.015%	-Face or Scalp arm (Referred to Face/Scalp arm): Apply ingenol mebutate gel 0.015% once daily for 3 consecutive days
DRUG	ingenol mebutate gel 0.05%	-Trunk or Extremities arm (Referred to Trunk/Extremities arm): Apply ingenol mebutate gel 0.05% once daily for 2 consecutive days

Timeline

• Start date: 2015-04-01
• Primary completion: 2016-06-01
• Completion: 2016-06-01
• First posted: 2016-03-23
• Last updated: 2018-04-18
• Results posted: 2018-04-18

Locations

1 site across 1 country: South Korea