Abstract
Purpose :
Neurotech’s novel product NT-501 is an encapsulated cell therapy (ECT) targeting treatment of Macular Telangiectasia Type 2. Aminoglycoside antibiotics are commonly administered to patients following ophthalmic surgery to prevent infection of the eye. During phase 3 clinical trials of NT-501, aminoglycosides were contraindicated for use with NT-501 due to their potentially cytotoxic effects. To support the use of these antibiotics with NT-501, the following study was conducted evaluating three critical quality attributes (cell viability, cell quantitation, and CNTF output).
Methods :
NT-501 drug product was treated in vitro with two of the most common aminoglycosides (Tobramycin and Gentamicin), as well as a fluoroquinolone Ofloxacin, which was used in NT-501 clinical trials [NCT#03319849]. Appropriate bioavailability of the vitreous was determined by literature review to be between 0.1 and 5%. Therefore, a 10% bioavailability (2x the maximum literature estimate) was targeted. Devices were treated daily over a 7 day period, to simulate the recommended NT-501 post-implantation administration schedule. Prior to administration of antibiotics, baseline device viability was evaluated by a metabolic activity assay, number of cells was evaluated by DNA quantitation, and output of the target therapeutic (CNTF) was evaluated by ELISA. These critical quality attributes were again evaluated after 7 days of antibiotic administration, as well as after an additional 7 day recovery period (total 14 days).
Results :
A two one-sided t-Test (TOST) for non-inferiority was performed on the cellular viability, cell number, and CNTF output of NT-501. For all three antibiotics, these critical quality attributes were shown to be non-inferior to their respective baselines (viability p<0.04, cell number p<0.01, CNTF output p<0.01).
Conclusions :
The findings of this study support the use of aminoglycosides such as Tobramycin and Gentamicin in addition to the use of fluoroquinolones such as Ofloxacin as treatment options for administration of antibiotics following surgical administration of NT-501. These results support the future use of aminoglycosides for similar ECT platform applications.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.