DEVELOP, QUALIFY IMMUNOLOGICAL ASSAYS, AND PROVIDE CLINICAL SAMPLE TESTING FOR AAV-BASED GENE THERAPY CLINICAL CANDIDATES

About This Grant

The contractor shall develop OR adapt/use previously developed (if available): anti-drug antibody (ADA) and neutralizing antibody (NAb) assays as well as T-cell immunogenicity assays to support NACTS clinical trials including the MMA-101 gene therapy candidate and implement the assays for testing of clinical samples for the FIH clinical trial of MMA-101. The contractor shall qualify OR use already available qualified anti-AAV8, anti-MMUT, AAV8 NAb assays, and anti-AAV8 and anti-MMUT T-cell assays. The NAb assay must be performed in a CLIA certified laboratory because its results will be used to determine eligibility of MMA patients for the FIH clinical trial of MMA-101. Clinical trial endpoints also include anti-AAV8 and anti-MMUT antibody levels and T-cell responses to AAV8 capsid proteins and MMUT (Elispot or Fluorospot). Thus, all these assays will need to be developed, qualified, and performed on clinical trial samples for the study. Not more than 50 MMA patients will be screened for eligibility (NAb assay). The anti-AAV8 and anti-MMUT tests will be performed for up to 6 research subjects at baseline and Study Days 5, 14, 42, 56, 84, 168, 364. The NAb assay will be performed at baseline, Study Days 5, 14, 42, 56, 84, 168, 364, and Years 2, 3, 4 and 5 post MMA-101 administration. Reporting of data must be CLIA compliant for the NAb test performed for study eligibility, and cGCP-compliant, per study protocol, for the NAB and anti-AAV8 and anti-MMUT assays performed throughout the execution of the FIH study. The T-cell assays will be performed for up to 6 research subjects at Study Days 56, 84, 168, ad 364 after MMA-101 infusion. Sample processing, shipping, results transmission, and all related activities must follow the qualified methods, clinical protocol, Laboratory Manual, and related documentation. Contractor shall develop controls, standards and critical reagents, and SOPs to support clinical trial sample testing for NCATS trials or studies of interest to NCATS. Contractor shall provide a written results summary with data and a complete study report (IND format) after all subtasks are completed, including: a) the plan for assay development OR adaptation (if assay already available) and implementation of NAb, anti-AAV8, anti-MMUT antibody assays, and T-cell assays; b) a detailed description of the assays; c) the plan for testing of the clinical trial samples, including CLIA-compliant NAb assay; and d) all test results from the evaluation of the clinical samples.