A Dose-Scheduling Study of AP001 and AP002 in the Treatment of Oral Mucositis Induced by Acute Radiation in Hamsters.

Principal Investigator: Stephen T. Sonis, DMD., DMSc, Department of Oral Medicine, Infection and Immunity Harvard School of Dental Medicine Divisions of Oral Medicine, Oral and Maxillofacial Surgery and Dentistry Brigham and Women’s Hospital and the Dana Farber Cancer Institute Boston, MA, USA.

Results

The mean mucositis scores for each group were evaluated on alternative days. The mean mucositis scores for treatment with AP002 were much lower than the vehicle control or an untreated control group. Vehicle-treated animals exhibited a peak mucositis score of 3.2 on Day 18 that had decreased to an average score of 2.5 by Day 24. The group dosed with 3μg of AP002 daily from Day 1 to Day 10 had a peak average mucositis score of 2.7 on Day 16 which had decreased to 1.8 on Day 24.

Results

To examine the levels of clinically significant mucositis, the total number of days in which an animal exhibited an elevated score was summed and expressed as a percentage of the total number of days scored for each group. Statistical significance of observed differences was calculated using chi-square analysis. Statistically significant changes were observed between the vehicle control group and all treatment groups (p value for AP002 group < 0.001).

1. Topical dosing of AP001 at 8μg/dose from Day -1 to Day 20 resulted in significant reduction in ulcerative mucositis duration compared to the vehicle-treated controls, an effect that was also observed in the previous studies, APS-02A and APS-02B.
2. 1. Treatment with AP001 at 8μg/dose on an abbreviated schedule, whether that schedule was from Day -2 to Day 4 or from Day 1 to Day 10, resulted in greater reductions in ulcerative mucositis than when AP001 was given from Day -1 to Day 20.
3. Treatment with AP002 at 3μg/dose produced similar reductions in ulcerative mucositis to the AP001 when given from Day -2 to Day 4 or from Day 1 to Day 10.
4. No adverse events were noted in animals treated with topically dosed AP002 or AP001 peptide forms.