Shire Plans Phase 4 Clinical Trial of Parathyroid Hormone Therapy

Shire plans a Phase 4 clinical trial of its parathyroid hormone therapy Natpara as an add-on to standard hypothyroidism treatment.

Hypoparathyroidism is caused by abnormal low levels of parathyroid hormone (PTH), which regulates levels of calcium in blood and bones. Low levels of the hormone lead to a  mineral imbalance that includes lack of calcium and vitamin D. Among the disease’s symptoms are fatigue, intolerance to cold, sleepiness, and depression.

Standard treatment consists of calcium and vitamin D supplements. But not all patients respond to it, with some having fluctuations in calcium levels.

Shire developed Natpara to help patients who are unable to stabilize their calcium levels with standard therapy. The treatment, called Natpar in Europe, is the first artificially produced full-length human parathyroid hormone.

A Phase 3 trial (NCT00732615) showed that daily injections of Natpara normalized calcium levels in blood while allowing 42 percent of the 124 patients to reduce their oral calcium and vitamin D doses.

The most common adverse events that Natpara-treated participants displayed were sensations of tingling, tickling, pricking, or burning of the skin, low or high blood calcium levels, headache, and nausea. The events occurred at similar rates in patients in the placebo group, suggesting that they may not be related to Natpara treatment.

The Phase 3 results led to the FDA approving Natpura in January 2015 — with some restrictions — and Naptar’s conditional approval in the European Union in April 2017. Conditional approval makes the therapies available to patients with unmet medical needs sooner.

An ongoing randomized Phase 1 trial (NCT02781844), also known as PARALLAX, is evaluating how the body handles twice-a-day doses of Natpara, compared with the once-a-day dose that regulators approved.

Shire is still recruiting patients for the PARALLAX study. Those who complete it will have the option of continuing treatment in an extension study (NCT03364738).

The company plans to enroll 150 hypoparathyroid patients aged 18-85 in the Phase 4 trial (NCT03324880). Its main objective is to see if a daily dose of Naptara improves the symptoms of patients on standard care.

Researchers are seeking participants who have had hypoparathyroidism for at least 12 months, and who are being treated with vitamin D alone or in combination with calcium supplements. Patients will be randomized to receive either a Natpara or placebo injection every day for six months.

Symptom improvement will be assessed at the beginning of the study and after six months of treatment. The yardstick will be patients’ Hypoparathyroidism Symptom Diary (HPT-SD) scores.

Researchers will also assess the treatment’s effect on metabolism, or the conversion of nutrition to energy, and treatment-associated adverse events.

Additional information about the trial can be found here.