Inhibition of Complement Factor 3 in Geographic Atrophy with NGM621: Phase 1 Dose-Escalation Study Results
| Autor: | Priya Chandra, Husam Younis, Charles C. Wykoff, Erin C. Henry, David A Eichenbaum, Alex DePaoli, Mark Solloway, Vrinda S. Hershberger, Nancy Yuan |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
medicine.medical_specialty
Visual acuity genetic structures Lesion Macular Degeneration Pharmacokinetics Geographic Atrophy Ophthalmology medicine Humans Fluorescein Angiography Adverse effect business.industry Complement C3 Macular degeneration medicine.disease Choroidal Neovascularization eye diseases Treatment Outcome Choroidal neovascularization Tolerability Pharmacodynamics Intravitreal Injections medicine.symptom business Tomography Optical Coherence |
| Zdroj: | American Journal of Ophthalmology. 235:131-142 |
| ISSN: | 0002-9394 |
| Popis: | Purpose To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential. Design Multicenter, open-label, single- and multiple-dose phase 1 study. Methods Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2 and best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, 15 mg) or received 2 doses NGM621 15 mg 4 weeks apart in the multidose phase and were followed for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments. Results All 15 participants completed the 12-week study. There were no serious adverse events and no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points. Conclusions In this small, open-labelled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect