SPIRIT 2, one of two pivotal Phase 3 clinical trials evaluating once daily relugolix pills combined with estradiol and progestin in treating pain in women with endometriosis, is now fully enrolled, its developer Myovant Sciences announced.
The safety and efficacy trial (NCT03204331), along with its twin study SPIRIT 1 (NCT03204318), is part of a Myovant program aiming at regulatory approval of relugolix in treating moderate-to-severe endometriosis pain. Top-line data are expected in the first months of 2020 for SPIRIT 2, and at mid-year for SPIRIT 1.
Enrollment in SPIRIT 1 is still underway at multiple sites in the U.S., Canada, Europe, Argentina, and South Africa. More information on these sites is available here.
“One in ten premenopausal women have endometriosis, a condition often associated with debilitating pain … and infertility. Currently, the standard of care for women with moderate to severe endometriosis is invasive procedures and pain medicines, including opioids,” Juan Camilo Arjona Ferreira, MD, Myovant’s chief medical officer, said a press release.
“We are developing relugolix combination therapy as a single pill taken once a day with the goal of offering patients a well-tolerated and effective alternative,” Ferreira added.
Relugolix is an investigational small molecule that blocks signals from gonadotropin-releasing hormone (GnRH), thereby lowering ovarian estrogen production. Estrogen is known to stimulate the growth of uterine fibroids, noncancerous growths that can lead to heavy menstrual bleeding and pelvic pain, which are associated with endometriosis.
Both these pivotal and worldwide studies, each enrolling about 600 adults up to age 50, aim to confirm the safety and efficacy of relugolix, combined with estradiol and progestin, in reducing endometriosis-associated pain.
Participants are being randomly assigned to one of three groups: the relugolix combination therapy, consisting of relugolix tablets (40 mg) plus capsules of estradiol (1.0 mg) and progestin (norethindrone acetate; 0.5 mg) once a day for 24 weeks; relugolix alone for 12 weeks, followed by the relugolix combination therapy for another 12 weeks; or to a placebo for 24 weeks.
Estradiol and progestin are forms of the female sex hormones estrogen and progesterone. They will be added to relugolix as a form of low-dose, hormonal add-back to help balance the relugolix-induced lowering of estrogen levels and to offset the effects this can cause, such as weakened bones and hot flushes.
The primary measure of effectiveness in each trial will be the changes in menstrual pelvic pain (dysmenorrhea) and non-menstrual pelvic pain reported by patients.
Safety outcomes, including bone mineral density changes as measured by bone densitometry (DEXA, DXA), will also be assessed.
Women completing either trial may continue in its open-label extension phase, in which all will be given the relugolix combination therapy for 80 weeks, allowing those in the initial investigative group to use the combo treatment for a total of 104 weeks. Its goal is to evaluate the safety of longer-term treatment, especially on bone health.
Myovant also is running a clinical program to assess the relugolix combination in treating women with heavy menstrual bleeding associated with uterine fibroids — the LIBERTY 1 (NCT03049735), LIBERTY 2 (NCT03103087), and LIBERTY-EXTENSION (NCT03412890) studies.
Relugolix given as a sole treatment, or monotherapy, is also been investigated in advanced prostate cancer patients, based on its ability to lower testosterone production in men.