185. Safety Study by Validated Immunoassays in a Phase III Study of Subjects with Inherited Retinal Dystrophy Due to Mutations in the Gene Encoding Human Retinal Pigment Epithelium-Specific Protein 65 (RPE65) Injected with Adeno-Associated Viral Vectors
| Autor: | Jean Bennett, Yifeng Chen, Romuald Corbau, Daniel J. Hui, Stephen R. Russell, Thomas Antrilli, Yun Liu, Katherine A. High, Albert M. Maguire |
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| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
medicine.diagnostic_test biology business.industry ELISPOT T cell Antibody titer law.invention Titer medicine.anatomical_structure Randomized controlled trial Tolerability law Immunoassay Drug Discovery Immunology Genetics medicine biology.protein Molecular Medicine Antibody business Molecular Biology |
| Zdroj: | Molecular Therapy. 24:S72-S73 |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/s1525-0016(16)32994-x |
| Popis: | Mutations in the gene encoding Retinal Pigment Epithelium-Specific Protein 65 (RPE65) cause impaired vision from an early age and eventually total vision loss later in life. Recent work by our group and others demonstrated the use of SPK-RPE65, an adeno-associated viral (AAV) vector, to deliver the gene stably in small and large animal models, while Phase 1 and Phase 3 clinical trials with SPK-RPE65 showed promising results (Maguire et al., 2008; Maguire et al., 2009; Simonelli et al., 2010; Maguire, AAO 2015). The Phase 3 trial was an open-label, randomized study using a subretinally-delivered AAV2 vector to augment the RPE65 gene. Thirty one subjects were enrolled from centers at The Children's Hospital of Philadelphia or University of Iowa. Twenty of the 21 intervention group subjects received 1.5E11 vg non-simultaneous injections to each eye. In addition to a separate efficacy assessment that measured the primary and secondary endpoints for the trial, an independent safety study was performed that included previously established immunological assays designed to monitor cellular immune responses. Two assays were subjected to further validation in-house and used for immune analysis of clinical samples obtained from all intervention subjects. An Enzyme-Linked Immunosorbent Assay (ELISA), capable of detecting a titer of at least 1.55 ug/mL anti-AAV2-capsid human IgG, was performed on 21 subjects covering up to 4 timepoints (baseline prior to injection, day 30, day 90 and 1 year). To better evaluate the results, the subjects were placed into 6 categories based on their antibody titer profile (Table 1Table 1).Table 1Anti-AAV2 Profile of Intervention Group (n=21)Number of SubjectsAnti AAV Titer Range (ug/mL)Anti-AAV2 Profile7 |
| Databáze: | OpenAIRE |
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