A Phase 2 clinical trial is recruiting adult women with endometriosis to evaluate the safety and effectiveness of an insertable vaginal ring of quinagolide to treat moderate to severe endometriosis pain.
Enrollment in the RAQUEL trial (NCT03692403) is ongoing at several sites across the U.S. Information about eligibility criteria is available here, and contacts and locations are found here.
Pain is one of the main symptoms for women with endometriosis, many of whom find it difficult to access quality care outside the limited number of specialized clinics. As a result, these women can often experience misdiagnosis, deficient care, and persistent symptoms.
In many cases, patients are placed on hormonal suppression to manage their pain but these medications relieve symptoms only temporarily and, in the case of gonadotropin-releasing hormone receptor analogs, are contraindicated for pregnancy with high costs and significant side effects, said Michelle E. Marvel, founder and executive director of the Endometriosis Research Center (ERC), in a press release.
“Safer and more effective therapies that can eliminate the actual lesions, prevent recurrence and effectively relieve pain are desperately needed,” she said.
Angiogenesis, the biological process of new blood vessel growth, is believed to play an important role in endometriosis and viewed as a promising target for new treatments.
Endometriotic lesions require an adequate blood supply to survive. The invasiveness of these cells — their ability to spread and establish elsewhere in the body — relies on the presence of an angiogenic-promoting environment.
Patients’ peritoneal fluid (the fluid inside the abdominal cavity) carries white blood cells, endometrial and red blood cells, many inflammatory cytokines (messenger molecules that mediate communication during immune responses), growth factors, hormones, and factors that promote angiogenesis (proangiogenic factors).
This complex mixture fosters the spreading of new blood vessels at endometriotic lesions and their surroundings, supporting their implantation and survival.
Thus, novel agents that block or attenuate this process may help reduce endometriotic lesions by reducing their blood supply.
Quinagolide, the active ingredient in the vaginal rings under development by Ferring Pharmaceuticals, is believed to reduce the levels of vascular endothelial growth factor (one of the most potent proangiogenic factors) and interleukin-6 (a cytokine associated with endometriosis development and severity).
The compound is approved in countries outside the U.S., including Canada and European countries, to treat high levels of the hormone prolactin (hyperprolactinemia).
Quinagolide is a non-ergot-derived selective dopamine D2 receptor, commonly called a dopamine agonist, that works by stimulating the receptors for dopamine, a neurotransmitter or chemical messenger that transmits signals sent by nerve cells. It is marketed as oral tablets under the brand name Norprolac, sold by Ferring.
In early studies, quinagolide demonstrated an acceptable safety profile, and was found not to affect pregnancy or fetal development.
RAQUEL was designed to investigate the effects of quinagolide, formulated in an extended-release vaginal ring, on moderate to severe endometriosis-related pain in adult women.
The study is a randomized, double-blind trial that will evaluate three doses of quinagolide, compared to a placebo (rings containing no active ingredient) during eight menstrual cycles in women with surgically confirmed endometriosis.
During the first part of the study, the women will be randomly assigned to receive rings containing one of three doses of quinagolide, or to a placebo. All patients will receive the vaginal ring at some point during the study.
The trial’s primary efficacy measure, or primary endpoint, will be the change in Numerical Rating Scale (NRS) scores for the worst endometriosis-related pain reported by patients in diaries. NRS is a 10-point subjective scale, with 0 indicating no pain and 10 indicating the worst.
Secondary endpoints will be evaluated, including dysmenorrhea (painful periods), non-menstrual pelvic pain, dyspareunia (pain during sex), vaginal bleeding, quality of life, painkiller use, hormonal levels, blood and urine tests, and heart exams.
“The currently available medical treatments for endometriosis all use a relatively crude approach of suppressing a woman’s estrogen,” said Andrew Cook, MD, an endometriosis specialist with centers in California and Colorado. “Unfortunately, endometriosis in some cases produces its own estrogen, rendering the medical treatments ineffective.”
“This novel, new approach may provide a new avenue of treatment of endometriosis, either alone or in combination with surgery to eliminate any remaining microscopic disease, with the potential benefit of increasing treatment success rates and decreasing recurrence rates,” he added.