Oral mucositis has a significant impact on patient quality of life and outcomes during cancer therapy as well as having a significant pharmacoeconomic cost. There are no currently approved drugs to treat oral mucositis in patients with non-hematological malignancies, including head and neck cancer (HNC). Soligenix is developing a new compound, SGX942, a modulator of the innate defense system, which binds to the p62 protein. p62 is a key adaptor protein that functions downstream of key sensing receptors of the innate defense system. Preclinical studies with SGX942 revealed a significant reduction in both duration and peak intensity of oral mucositis in both a fractionated radiation-induced hamster model of oral mucositis and a chemotherapy- induced mouse model of oral (tongue) mucositis: there was ~50% reduction in the duration of severe mucositis. Efficacy was dose responsive and optimal at 25 mg/kg dosed every third day during fractionated radiation therapy. Based on the preclinical findings, we hypothesize that SGX942 will be a safe and effective therapy for chemotherapy and radiation induced mucositis, allowing for better long-term cancer-related outcomes. Therefore, SGX942 warrants further clinical investigation. A placebo-controlled Phase 1 study in 84 healthy volunteers has been completed under a clinical trial application (CTA) filed with Health Canada, demonstrating that single intravenous (IV) doses of SGX942 were well tolerated up to the maximum tested (8 mg/kg) and daily IV doses were well tolerated up to the maximum tested (6.5 mg/kg for 7 days). No adverse events or toxicities were reported. On February 20, 2013, Soligenix submitted an investigational new drug application (IND) that included the clinical protocol for Study IDR-OM-01 entitled, "A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging, Multicenter Study of SGX942 for the Attenuation of Oral Mucositis in Patients Being Treated with Concomitant Chemoradiation for the Treatment of Squamous Cell Carcinoma of the Head and Neck." The IND completed the 30-day review period on March 22, 2013 and is now effective. The proposal requests funding to support the conduct of the Phase 2 clinical study IDR-OM-01. Approximately 75 patients will be enrolled at 15-25 clinical centers in the US with recently diagnosed cancers of the oral cavity and pharynx who are planned to receive chemoradiation treatment (CRT) into 3 treatment groups (1:1:1) including placebo, SGX942 1.5 mg/kg and SGX942 6.0 mg/kg. The study is designed to include 50 experimental (SGX942) subjects and 25 control (placebo) subjects. This is an exploratory study to enable estimation of patient responses for future studies and to establish proof of concept.
Specific Aim 1. Evaluate the efficacy of SGX942 compared to placebo in attenuating the onset of severe oral mucositis in patients receiving CRT for the treatment of HNC.
Specific Aim 2. Evaluate the safety of SGX942 in patients receiving CRT for the treatment of HNC.
Oral mucositis generally occurs as a debilitating adverse side effect of chemotherapy and radiation treatment for cancer and can cause patients to modify/delay treatment of their cancer. Oral mucositis is particularly common and severe in patients with head and neck cancer and there is no approved therapy for these patients. SGX942 is a new compound, targeting the hypothesized underlying cause of mucositis, that will be tested for its ability to decrease severe oral mucositis in patients receiving chemoradiation fo their head and neck cancer.