Phase Ⅰ/Ⅱ Clinical Trial for Regeneration of the Vocal Fold with Hepatocyte Growth Factor in Patients with Vocal Fold Scar and Sulcus

Abstract

The vocal fold mucosa has vibratory properties that are supported by specific histological structures, including the layer structure and wide distribution of hyaluronic acid. When the mucosa is scarred, the vibratory property is deteriorated, which leads to severe permanent dysphonia. No optimal treatment has yet been established. Hepatocyte growth factor (HGF) has a strong anti-fibrotic function and has been proven to resolve fibrosis and regenerate the original tissues in lung and kidney in animal experiments. We have additionally shown that HGF can resolve fibrotic tissues in vocal fold scars and improve the vocal function in animal models. Based on these pre-clinical data, a phase I/II exploratory clinical trial was planned for the assessment of the regeneration of the vocal fold in patients with vocal fold scar and sulcus. A GMP-compatible recombinant human HGF protein drug (KP-100LI; Kringle Pharma, Inc., Osaka) was injected into the scarred vocal folds under topical anesthesia. Three different dosages (1, 3, and 10 µg) for 1 side of the vocal fold were used for each group of patients. The injection was repeated weekly, up to four times. The patients were followed for six months after the treatment. The results indicated significant improvement of the vocal fold vibratory amplitude, voice handicap index (VHI)-10, and GRBAS scale. No severe adverse events were noted. These findings suggest that HGF is effective for promoting regeneration of the vocal fold in patients with vocal fold scar and sulcus.