Photosensitizer Radachlorin®: Skin cancer PDT phase II clinical trials

Summary“Radachlorin”®, also known in the EU as Bremachlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution, was introduced into the Russian Pharmacopoeia. Its GMP (Good Manufacturing Practice) facility based manufacturing method was patented. Laboratory experiments and clinical phase I were performed.Protocols were designed for PDT of basal cell carcinoma of the skin to result in GCP (Good Clinical Practice)-conformed randomized phase II clinical studies. “Radachlorin”® solution for intravenous infusions 0.35% 10 mL in the doses of 0.5–0.6 and 1.0–1.2 mg/kg and a gel for topical application 0.1% 25 g in the dose of 0.1 g/cm2 were photoactivated by 2.5W 662 nm semiconductor laser “LAKHTA-MILON®” (St. Petersburg, Russia) in light doses of 200, 300 (solution), 400, 600, 800 (gel) J/cm2.Safety study showed no side effects and a good tolerability of “Radachlorin”® by patients. There was no normal skin/subdermal tissue damage after both laser and sun light exposure. The main part (98%) of the drug was excreted or metabolized in the first 48 h. Drug administration at a dose of 1.0–1.2 mg/kg and irradiation at 3 h with 662 ± 3 nm light at a dose of 300 J/cm2 (solution) and 4 PDT sessions at an interval of 1 week with 3 h gel exposure, followed by 400 J/cm2 light exposure (gel) were found to be the optimal treatment regimes.Having successfully passed clinical trials, “Radachlorin”® achieved marketing authorization in Russia in 2009 and a conditional approval in South Korea in 2008. It is a candidate for phase III clinical trials in the EC and may be commercialized as a prospective second-generation photosensitizer.