Phase 2 Trial of TransCon PTH to Speed Enrollment of Patients Affected by U.S. Recall of Natpara

A Phase 2 trial testing the experimental therapy TransCon PTH in adults with hypoparathyroidism is expanding to allow for faster enrollment of people previously treated with Natpara (parathyroid hormone, PTH), which was recently recalled in the United States.

Developed by Ascendis Pharma, TransCon PTH is intended to restore PTH levels within 24 hours. It is a prodrug, which means it is an inactive molecule that is metabolized within the body to form the active agent, which in this case is PTH.

The PaTH Forward study (NCT04009291), sponsored by Ascendis, is designed to evaluate Transcon PTH’s safety and efficacy. Information on contacts and study locations in the U.S., Europe, and Canada can be found here. Those interested in enrolling should consult with their healthcare provider first, the company said.

In September, Takeda issued a U.S. recall of Natpara following concerns of potential contamination of the therapy by small rubber fragments detaching from the product’s protection cap.

“This has been one of the most challenging times in the history of the hypoparathyroidism community, as we have navigated both the emotional and physical impact of the only PTH replacement therapy available being recalled in the U.S.,” Deb Murphy, president of the HypoPARAthyroidism Association and vice chair of its board of trustees, said in a press release.

“We are grateful and very excited about Ascendis Pharma’s efforts to expedite participation in the PaTH Forward Trial for additional patients,” Murphy added.

PaTH Forward was initially planning to enroll 40 adults with hypoparathyoridism who are managing their condition with the vitamin D analog calcitriol at least twice a day or the vitamin D byproduct alfacalcidol at least once a day, along with calcium supplements taken at least twice a day.

Prior to this expansion, people who had undergone treatment with Natpara were required to undergo a long “washout” period before being allowed to enter screening for PaTH Forward. With the protocol changes, these individuals will have a faster path for enrollment, which, according to Ascendis, is expected to result in recruitment of more than the anticipated 40 participants.

“The unexpected recall of Natpara in the U.S. has had a major impact on my patients who have not been optimally controlled on standard of care with vitamin D and calcium supplements,” said Mishaela Rubin, MD, one of the trial investigators.

“Patients living with hypoparathyroidism have an acute need to manage both their short-term symptoms and reduce risk of long-term complications,” she added. “The PaTH Forward trial is an opportunity for patients to participate in evaluation of a new potential treatment option.”

To meet the study’s primary goals, patients’ blood calcium levels and the percentage of calcium filtered by the kidneys must be normalized after treatment, or decrease by 50% without the need for vitamin D supplementation or more than 1 g of a daily calcium supplement.

Participants will be randomly assigned to one of three doses of TransCon PTH (15, 18, or 21 μg per day) or a placebo for four weeks, all given once daily via under-the-skin injection with a pre-filled pen. After completing the study, patients will have the option of moving to a long-term extension trial.

PTH is normally secreted by the parathyroid gland and helps regulate levels of calcium and phosphate in the body. A Phase 1 trial (ACTRN12617001375347) found that TransCon PTH sustained release of PTH in the blood of healthy volunteers for more than 60 hours, supporting once-a-day administration. The treatment was also designed to normalize calcium levels in blood and urine, serum phosphate levels, and bone turnover.

Of note, TransCon stands for “transient conjugation.” TransCon molecules have three components: an unmodified parent therapy, an inert carrier that protects it, and a linker that binds the other two parts.