Nasal Safety of Chronic Intermittent Use of INP104: Results From the Phase 3 Open-Label STOP 301 Study
posted in Presentations by Brooke Eger
Poster presented at the 2021 American Headache Society (AHS) Virtual Annual Scientific Meeting.
Authors: Greg Davis, MD, MPH, Adil Fatakia, MD, Seth Pransky, MD, Alison E. Heald, MD, Sheena K. Aurora, MD, Jasna Hocevar-Trnka, MD, Stephen B. Shrewsbury, MB ChB
To assess the safety and tolerability of chronic intermittent use of INP104 (under development) on the nasal mucosa for 24/52 weeks in an open-label, Phase 3 clinical trial (STOP 301).
The STOP 301 study was designed to evaluate the safety and tolerability of INP104, a combination drug-device product of dihydroergotamine mesylate administered to the upper nasal space by a Precision Olfactory Delivery (POD®) device, for the acute treatment of migraine over 24 or 52 weeks. The primary endpoints were the number of patients with serious and non-serious treatment-emergent adverse events (TEAEs) change in nasal mucosal integrity, and change in olfactory function.
A standardized objective safety assessment instrument for the upper nasal space was not previously available. A Nasal Safety Review Committee (NSRC), consisting of 3 independent otolaryngologists, participated in the development and evaluation of nasal safety monitoring tools, which included the Quantitative Scoring Scale for Evaluation of the Nasal Mucosa (QSS-NM; scores of mucosal irritation = 0-5, epistaxis = 0-3, mucosal edema = 0-3, nasal discharge = 0-3, and mucosal crusting = 0-3), the University of Pennsylvania Smell Identification Test (UPSIT), and nasal adverse event (AE) reporting. Specific attention was given to the relationship between endoscopic mucosal examination grading (QSS-NM), UPSIT changes, and nasal-related TEAEs.
360 patients with episodic migraine were enrolled and 354 treated ≥1 self-reported migraine (full safety set, FSS) of whom 262 completed the first 24 weeks. A total of 73 patients entered the 28-week extension, with 66 completing 52 weeks of treatment, with a total of 6332 doses of INP104 administered. Nasal AE monitoring revealed that 162 patients (45.8%) reported a nasal-related TEAE in the 24-week FSS, of which none were serious. The most common (incidence ≥ _10%) nasal-related TEAEs were nasal congestion (n=59, 16.7%) and upper respiratory tract infection (URTI; n=38, 10.7%). Nasal-related TEAEs were mild or moderate with a single severe nasal-related TEAE (of nasal congestion). TEAEs of nasal congestion led to treatment discontinuation in only 5 (1.4%) patients. Over 90% of patients had normal upper nasal endoscopies reported throughout the 24-week trial. Clinically significant changes were noted in 4 patients at Week 4, 3 patients at Weeks 8 and 12, but none at Weeks 24, 36, or 52. Only 4 patients had a total QSS-NM score change of >7 points (sum of left + right), while 12 patients had a change of ≥2 on any one of the 5 items over 24 weeks. Endoscopy or QSS-NM score changes were associated in 22 of 26 cases of unrelated or unlikely to be related TEAEs over 52 weeks. No increase in TEAE frequency was noted to be related to more frequent or longer duration of dosing. 25 patients had an UPSIT score decrease of 5 or more points over 52 weeks, and associated TEAEs were asymptomatic (17), associated with URTI or sinus symptoms (9), and mild hyposmia (2) without other upper respiratory symptoms. No safety concerns were raised by the NSRC based on review of all data.
Patient-reported AEs were sufficient to monitor safety of intermittent use of INP104. Nasal endoscopies and physiological tests did not add additional clinical value.
Davis G, Fatakia A, Pransky S, Heald AE, Aurora SK, Hocevar-Trnka J, Shrewsbury SB, Nasal Safety of Chronic Intermittent Use of INP104: Results From the Phase 3 Open-Label STOP 301 Study, 2021 American Headache Society (AHS) Virtual Annual Scientific Meeting.