Based on an interim blinded analysis of the first group of the more than 80 patients who have now completed the trial at 16 weeks, the study has shown improvement in polyposis by endoscopy in about 50 percent of patients (N=43) and improvement in sinus inflammation by CT scan in approximately 50 percent of patients (N=23). Moreover, 50 percent of patients with objective evidence of improvement have achieved the primary endpoint of complete resolution of cardinal symptoms.
In order to put the blinded analysis into perspective, it is important to appreciate the study design. The study population is in patients who have undergone one or more sinus surgeries for CS, but who are struggling with recurrent severe CS as determined by symptoms, endoscopy, and CT scan of the sinuses.
The trial is intended to test the efficacy and safety of SinuNase? (intranasal amphotericin B 0.01% suspension) lavage for the treatment of severe refractory chronic sinusitis. All patients entering the trial and all patients after two weeks of saline irrigations must have the two cardinal symptoms of CS. To date, no patient has had resolution of either cardinal symptom after two weeks of saline irrigations. Subsequently, patients are randomized in a double-blind fashion on a 1:1 ratio with 50% of patients using SinuNase and 50% using a placebo control. The primary endpoint is complete resolution of both key cardinal symptoms of chronic sinusitis at 16 weeks. The protocol includes questions about symptoms and nasal endoscopy performed throughout the trial at scheduled intervals, with CT scans of the sinuses taken at the beginning and end of the trial for each patient.
Based on an interim blinded analysis of the first group of the more than 80 patients who have now completed the trial at 16 weeks, the study has shown improvement in polyposis by endoscopy in about 50% of patients (N=43) and improvement in sinus inflammation by CT scan in approximately 50% of patients (N=23). Moreover, the interim data shows that almost 50% of these patients with objective evidence of improvement have achieved the primary endpoint of complete resolution of the two key cardinal symptoms. The Company cautions that these are blinded interim results and that although the positive correlation of symptom resolution with objective evidence of improvement by endoscopy and CT scan suggests that SinuNase is demonstrating the anticipated efficacy compared to control, only unblinded data will determine if the SinuNase arm of the trial has achieved the primary endpoint versus control in a statistically significant manner. When Accentia designed the clinical trial, the Company projected that approximately 4% of all patients would need to achieve the primary endpoint assuming a null hypothesis (no effect) for the control group. The interim blinded data shows that approximately 23% of all patients are achieving the primary endpoint of complete resolution of both cardinal symptoms and approximately 27% of all patients have achieved complete resolution of one or the other of the two cardinal symptoms (N=48).
Furthermore, Accentia reports that it appears that patients are experiencing substantial symptom resolution and reduction in polyposis by 2-4 weeks. Accordingly, the Company believes that if analysis of unblinded data at the conclusion of the trial documents that SinuNase is indeed effective by Week 4, the second pivotal Phase 3 trial may be adjusted to be an 8-week trial rather than 16-weeks.
Accentia reiterates its goal of completing enrollment in the trial before the end of the summer in order to have unblinded top line results around the end of the year. The clinical investigators in the trial have evaluated over 600 candidates, of which over 100 otherwise qualified patients to date were rejected because their initial sinus inflammation as judged by CT scan did not qualify as severe enough to meet the standards of the trial. Accordingly, the Company currently has over 90% enrollment in the 300 patient trial but it cannot predict with certainty the date of enrollment completion because of the strict entrance criteria as they relate to CT scan of the sinuses.
The Company does not anticipate providing additional interim analyses of blinded data. The Company has continued a black out period for trading during which directors, officers, and employees of the Company (insiders) can not engage in open market stock transactions until the unblinding of the Phase 3 clinical trial and the public release of the results. On a case-by-case basis, the Board may consider allowing private purchases of stock by insiders when the seller acknowledges in writing that the purchaser is an insider privy or potentially privy to material non-public information.