A Phase 3 trial evaluating Corcept Therapeutics‘ relacorilant in treating the high blood pressure and poorer glucose tolerance in people with endogenous Cushing’s syndrome has begun dosing patients in Europe, the company announced.
The GRACE trial (NCT03697109) will be conducted at 62 sites in the United States, Canada, Europe, and Israel. Currently, 43 sites in the U.S. and Europe are open and enrolling patients, and the company expects to “open an additional 13 sites by the end of the year,” Andreas Grauer, MD, Corcept’s chief medical officer, said in a press release.
More information, including contacts, on study sites now recruiting can be found here.
Patients with endogenous Cushing’s syndrome have an “internal” (endogenous) culprit — usually a benign tumor in the pituitary or adrenal glands — that triggers excessive cortisol production. This can lead to serious problems, such as type 2 diabetes and high blood pressure.
Relacorilant was designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor.
In an earlier and now completed Phase 2 trial (NCT02804750), relacorilant improved glucose tolerance and lowered blood pressure in patients faster and with fewer side effects than approved medications.
The trial also met several of its secondary goals, including improvements in liver function, blood flow, insulin resistance, cognitive function, mood, and quality of life.
These findings support relacorilant as a potential standard treatment for managing the effects of prolonged cortisol excess in Cushing’s patients. The newly opened Phase 3 trial is needed to confirm them.
GRACE will compare relacoritant to placebo in up to 130 patients with endogenous Cushing’s syndrome and concurrent type 2 diabetes mellitus, impaired glucose tolerance, and/or uncontrolled high blood pressure.
It is being conducted in two parts. First, all patients will be given oral relacorilant once daily for 22 weeks, at doses rising from 100 mg to a maximum of 400 mg. Patients who complete this first part and show improvements in pre-specified measures of glucose tolerance or blood pressure will then move into its second, randomized (placebo group) part.
Here, patients will be randomly assigned to either continued relacorilant treatment at the same dose they were receiving in part one, or to being given a placebo instead. This second round will last 12 weeks.
GRACE’s primary outcome is to evaluate changes in glucose tolerance and blood pressure during the trial’s second part, as well as safety, which will be evaluated for a total of 48 weeks.
“Our investigators are highly enthusiastic about GRACE, because of relacorilant’s positive Phase 2 efficacy and side effect profile,” said Grauer, adding that the company plans to ready for submission an application requesting regulatory approval by the end of 2021.
Corcept also plans to launch another Phase 3 trial testing relacorilant in patients whose Cushing’s syndrome is caused by a benign adrenal tumor. These patients often have poor outcomes.
This study is expected to open in early 2020, and aims to enroll up to 130 patients at sites in the U.S. and Europe, potentially at sites also participating in GRACE.