Ascendis Planning Phase 2 Trial Testing Efficacy, Safety of Investigational TransCon PTH Therapy
Ascendis Pharma is planning the design of its upcoming Phase 2 clinical trial intended to assess the efficacy and safety of its proprietary, investigational TransCon PTH therapy in adults with hypoparathyroidism.
The latest data from the TransCon PTH clinical program was presented in a poster titled, “The design of a long-acting PTH (TransCon PTH) phase 2 trial in patients with hypoparathyroidism, based on phase 1 results in healthy subjects” (abstract#338), at the 46th Annual Meeting of the European Calcified Tissue Society (ECTS), recently held in Budapest, Hungary.
TransCon PTH is a long-acting pro-drug — a compound that needs to be metabolized to release the active agent — designed to restore the levels of the parathyroid hormone (PTH) within 24 hours in patients with hypoparathyroidism. In doing so, the therapy also promotes the normalization of calcium levels in the blood and urine, as well as serum phosphate levels, and bone turnover.
In an earlier Phase 1 trial (ACTRN12617001375347), TransCon PTH was shown to be, in general, safe and well-tolerated in healthy volunteers. Treatment with this investigational therapy also showed sustained release of PTH into the blood, which lasted for more than 60 hours in circulation, supporting once-a-day administration.
The effects were similar to those reported with infusion-based PTH therapies, which have been the most effective strategies to date in bringing PTH levels close to normal, according to the company.
Based on these findings, Ascendis is planning its Phase 2 PaTH Forward trial, aiming to further test the safety and efficacy of daily treatment with TransCon PTH.
The trial is expected to enroll approximately 40 adults with hypoparathyroidism from multiple clinical sites worldwide. Participants will receive TransCon PTH at a dose of 15, 18, or 21 μg, or placebo, for a period of four weeks. The treatment with be given with a ready-to-use prefilled pen device.
To meet the trial’s primary endpoint, patients’ blood calcium levels and the percentage of calcium filtrated by the kidneys must be within a normal range after treatment, or decrease by 50% from the beginning of the study. Participants should not need to take active vitamin D, or more than 1000 mg of calcium supplements per day, to achieve or maintain normal levels.
Researchers also will determine the best disease-specific, patient-reported outcomes for assessing and validating the treatment’s efficacy. Those would be used in future Phase 3 studies.
All participants will be eligible to for the study’s long-term extension, in which the doses of TransCon PTH will be optimized to suit each patient’s individual needs.
“The Phase 2 trial is designed to support the TransCon PTH target profile as a true PTH replacement therapy while confirming the starting dose in Phase 3,” the researchers said.
Ascendis Pharma is seeking approval by the U.S. Food and Drug Administration to launch the Phase 2 trial, and expects to announce its top-line data during the fourth quarter of 2019.
The positive early results and the advancement of TransCon PTH into clinical studies with hypoparathyroidism patients reflects Ascendis Pharma’s “strong commitment to patients and science,” Jan Mikkelsen, president and CEO, said in a press release.
Ascendis Pharma is currently involved in regulatory discussions to incorporate Asian territories into future Phase 3 clinical studies.