MMA-101 (AAV8-MMUT) as a Gene Therapy For Methyl Malonic Acidemia

National Center For Advancing Translational Sciences

Investigators

Abstract

To ensure the timely initiation of the clinical trial, we and the other participating ICs (NHGRI, NINDS, NICHD, and NIH CC/ORSC) have executed legal agreements (Memorandum of Understanding and Clinical Trials Agreement) and set up a trial oversight Steering Committee. In addition, we initiated the clinical trial database build using the CiSTAR platform (NINDS), assembled the clinical operations team, planned for the Data and Safety Monitoring Board (DSMB) activities, finalized the clinical protocol and associated documents, prepared the device compatibility study testing plan, and are developing the bioanalytical methods to be used during clinical sample testing. Batches of clinical grade / current Good Manufacturing Practice (cGMP)-compliant MMA-101 product have already been manufactured. Stability testing of the cGMP MMA-101 and diluent has continued, to ensure they maintain the quality required for use in the upcoming trial. Similarly, we continued the stability testing for cGMP-grade 1-13C-propionate, as this reagent is used in evaluating a primary endpoint in the clinical trial. We performed a regulatory review of the IND documentation for MMA-101, with finalization pending review from the Contracting Manufacturing Organization (CMO) that produced the MMA-101 investigational product and is conducting the stability testing. This will enable filing the IND application to begin clinical evaluation at the NIH Clinical Center.