Protara announces alignment with FDA on path forward for IV Choline Chloride

Protara Therapeutics has reached alignment with the U.S. Food and Drug Administration on a registrational path forward for intravenous Choline Chloride, an investigational phospholipid substrate replacement. The Company had previously been pursuing an indication in intestinal failure-associated liver disease and following feedback from FDA, will now pursue a broader indication in patients on parenteral nutrition who are or may become unable to synthesize choline from oral or enteral nutrition sources. The Company plans to advance the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PN. The FDA has granted IV Choline Chloride Orphan Drug Designation for the prevention of choline deficiency in PN patients. Choline is recommended for patients on PN by the American Society for Parenteral and Enteral Nutrition Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi-Trace Element Products, as well as by the European Society for Clinical Nutrition and Metabolism in their Guideline on Home Parenteral Nutrition. The FDA indicated that a single study with an endpoint of restoring choline levels in PN patients could serve as the basis for a regulatory filing for IV Choline Chloride. Based on this feedback, the Company intends to assess the safety and efficacy of IV Choline Chloride in its planned seamless Phase 2b/3 double-blinded, randomized, placebo-controlled THRIVE-3 study in adolescents and adults on long-term PN when oral or enteral nutrition is not possible, insufficient, or contraindicated. The Phase 2b portion of the study, which will seek to establish the pharmacokinetics profile of IV Choline Chloride, will enroll approximately 24 patients who will receive one of three daily doses of IV Choline Chloride for 24 weeks. During the randomized, double-blind Phase 3 portion of the study, approximately 100 patients will receive either high dose IV Choline Chloride, low dose Choline Chloride, or placebo for 24 weeks. The primary endpoint of this portion of the study will seek to demonstrate IV Choline Chloride as a durable source of choline. Secondary endpoints will assess the impact of choline replacement on liver function. All patients will be eligible to enter an open-label extension. The Company intends to initiate this study in the first half of 2025. In previous studies, treatment with IV Choline Chloride successfully increased plasma choline concentrations in patients on PN and was also shown to improve steatosis, a key marker of liver injury.