Research Project
9409741
7. Project Summary/Abstract This proposal supports the conduct of the clinical study IDR-OM-02 entitled, ?A Pivotal, Double-Blind, Randomized, Placebo-Controlled, Multinational Study of SGX942 (Dusquetide) 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?. This trial is designed to confirm the positive findings seen in the SBIR Phase I (R43DE024032) supported 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?. Oral mucositis (OM) is a serious and debilitating condition and currently an unmet medical need for patients and physicians. It 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 OM in patients with non-hematological malignancies, including head and neck cancer (HNC). Severe OM (i.e., WHO grades 3 or 4) is the most clinically important form as they have the potential to result in alterations to a patient's cancer therapy. OM has been linked to the dysregulation of the innate defense system, resulting in an inflammatory cascade, which amplifies damage to the mucosal lining leading to clinically overt mucositis. Dusquetide (the active pharmaceutical ingredient in SGX942) is an Innate Defense Regulator (IDR), which binds to the p62 protein, a key adaptor protein which functions downstream of most innate immune receptors. SGX942 has received Fast Track Designation from the FDA validating it has demonstrated the potential to address this unmet medical need. SGX942 can address both acute trauma and acute infections, and SGX942 may have some independent direct anti-tumor activity via its activity in the innate immune system. This Phase II proposal seeks to conduct a study to confirm that SGX942 (1.5 mg/kg dusquetide) is an efficacious therapy for chemoradiation therapy (CRT) induced severe OM in patients with HNC, allowing for better long-term cancer-related outcomes. If successful, results from this study will support marketing authorization applications worldwide, including a New Drug Application (NDA) submission to the FDA. The Specific Aims of this proposal are: Specific Aim 1. Confirm the efficacy of 1.5 mg/kg SGX942 compared to placebo in reducing the duration of severe oral mucositis (SOM) in patients receiving CRT for their oral cavity or oropharyngeal squamous cell carcinoma. Specific Aim 2. Confirm the safety of this immunomodulator in HNC patients including the lack of interference with chemoradiation treatment outcomes (tumor progression and mortality) and the lack of an increased infection rate with 1.5 mg/kg SGX942 treatment compared to placebo.
