A first patient has been dosed in a Phase 3 trial testing relacorilant as a possible treatment for Cushing’s syndrome, the investigative treatment’s maker, Corcept Therapeutics, announced a press release.
The trial, called GRACE (NCT03697109), is enrolling up to 130 endogenous Cushing’s patients at clinical sites in the U.S., Canada and Europe. To be eligible, patients must have concomitant type 2 diabetes, impaired glucose tolerance, or high blood pressure — all common consequences of prolonged excess cortisol (hypercortisolism).
Relacorilant, also known as CORT125134, is designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor. Interim data from an ongoing Phase 2 trial (NCT02804750) suggests that relacorilant may effectively manage the effects of hypercortisolism in Cushing’s patients.
Those treated with that trial’s lowest dose had a significant improvement in their glucose tolerance and a 60% increase in blood osteocalcin (a marker of bone health). Treatment also reduced the blood pressure in 45% of patients with uncontrolled high blood pressure from cortisol excess.
Importantly, results recorded after 12 weeks of relacorilant use were similar to those seen after six months of treatment with Korlym (mifepristone), an approved Cushing’s treatment also by Corcept. Side effects associated with this medicine, however, were not evident.
“Patients in Phase 2 experienced significant clinical benefit without Korlym’s serious off-target effects — endometrial thickening, vaginal bleeding and hypokalemia” said Joseph Belanoff, MD, Corcept’s chief executive officer. “Confirming these results in Phase 3 would constitute a major medical advance.”
The GRACE trial will be conducted in two stages. First, all patients will be given oral relacorilant for 22 weeks, at doses rising from 100 mg daily to a maximum of 400 mg each day.
Those who show improvements in pre-specified parameters of glucose tolerance or hypertension will then move into the second, randomized and placebo-control phase of the study.
Here, patients will be randomly assigned to either a placebo or relacorilant, given at the highest dose used in the open-label phase. Treatment will continue for 12 weeks.
The trial’s main objective is to determine the changes in glucose tolerance and blood pressure between the end of the study’s first and its second stage. Researchers will also assess the therapy’s safety by evaluating the number of treatment-related adverse effects over up to 48 weeks of follow-up.
Secondary goals include the proportion of patients achieving a response in glucose tolerance and high blood pressure criteria, changes in quality of life, and the proportion of patients whose disease worsened.
Patients who are not eligible for the randomized second part of this trial, and those who complete the randomized part, will be eligible to enter an extension safety study. Interim results from GRACE are expected by the end of 2020.
Test sites in five U.S. states are now open and recruiting eligible patients; information is available here.