A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of EN3285 for the Prevention or Delay to Onset of Severe Oral Mucositis in Subjects with Head and Neck Cancer Receiving Chemoradiotherapy

INTERVENTION: Product Name: NAC ProGelz® (NAC Oromucosal Liquid) Product Code: EN3285 Pharmaceutical Form: Oromucosal liquid* CAS Number: 616‐91‐1 Current Sponsor code: EN3285 Other descriptive name: N‐Acetylcysteine Concentration unit: % (W/W) percent weight/weight Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Oromucosal liquid* Route of administration of the placebo: Oromucosal use CONDITION: Severe Oral Mucositis ; MedDRA version: 9.1 Level: LLT Classification code 10028130 Term: Mucositis oral PRIMARY OUTCOME: Main Objective: The primary objective of this study is to evaluate the relative efficacy of EN3285 compared with placebo in the delay to onset of severe (NCI grade >2) OM. The coprimary objective of this study is to evaluate the relative efficacy of EN3285 compared with placebo in prevention of severe (NCI grade >2) OM at a cumulative dose of 50 Gy. Primary end point(s): The primary endpoint will be radiation dose to onset of severe OM (NCI grade >2) over the cumulative dose range 0 to 50 Gy.; ; The coprimary endpoint will be the proportion of subjects with severe OM (NCI grade >2) at a cumulative dose of 50 Gy.; ; The study will enroll subjects who are scheduled to receive a minimum cumulative RT dose of 60 Gy during a treatment period of up to 8 weeks. Due to the high variability of the treatment regimens not only across centers, but between subjects, this study will look at group comparisons up to and at a cumulative RT dose of 50 Gy. ; Secondary Objective: The secondary objectives of the study are to compare EN3285 with placebo with respect to:; • Safety through the collection of AEs and laboratory data; • Delaying the onset of severe OM (WHO grade >2) ; • Prevention of severe OM (WHO grade >2); • Percent of time (days) spent on opiates for oral pain during the course of RT ; • Reducing the need for interventional placement of feeding tubes for nutritional support due to OM; INCLUSION CRITERIA: Subjects will be included in the study if they: • Are 18 years and older with newly diagnosed clinically and histologically confirmed SCC of the oral cavity and/or oropharynx, and are intended for treatment with ChemoRT. (Subjects with unknown primary tumors are allowed depending on target RT as defined below as well as postoperative subjects.) • Have a clinical plan to receive a minimum of 60 Gy to the oral cavity and/or oropharynx using any of the following: – Standard fractionation to deliver 1.8 to 2.2 Gy per day in a single fraction – Intensity Modulated Radiotherapy (IMRT) and Helio IMRT are allowed • Will receive chemotherapy consisting of one of the following regimens: – Cisplatin 80 ‐ 100 mg/m2 in 21‐day cycles – Weekly cisplatin 30 mg/m2 • Have a WBC =3500 per cubic millimeter • Have a platelet count =100,000 per cubic millimeter • Have adequate renal function as determined by the principal investigator prior to enrollment