SPIRIT EXTENSION
Research type
Research Study
Full title
SPIRIT EXTENSION: An International Phase 3 Open-Label, Single-Arm, Safety and Efficacy Extension Study to Evaluate Relugolix Co-Administered with Low-Dose Estradiol and Norethindrone Acetate in Women with Endometriosis-Associated Pain
IRAS ID
246692
Contact name
Nicholas Raine-Fenning
Contact email
Sponsor organisation
Myovant Sciences GmbH
Eudract number
2017-004066-10
Clinicaltrials.gov Identifier
076642, IND Number
Duration of Study in the UK
1 years, 5 months, 29 days
Research summary
RESEARCH SUMMARY:
Endometriosis is a common chronic condition, occurring in women of reproductive age, where tissue that behaves like the lining of the womb (endometrium) is found in other parts of the body such as the ovaries and fallopian tubes. Each month, these cells react in the same way to those in the womb, building up and breaking down and bleeding. This can lead to chronic pain and infertility. The exact prevalence of endometriosis is unknown but estimates range from 2-10% of women of reproductive age, with symptoms ranging from minimal to severely debilitating.
Relugolix is being developed as a treatment of endometriosis-associated pain. Relugolix blocks certain receptors in the pituitary gland (a pea-sized gland located in the brain, involved in hormone control), leading to suppression of oestradiol (a female sex hormone, essential for reproductive tissue and bone development/maintenance).
This SPIRIT EXTENSION study is an international phase 3 open-label, single-arm, long-term efficacy and safety study that will enrol eligible participants who have completed the phase 3, randomised, double-blind, placebo-controlled parent study: SPIRIT 2. Approximately 800 women (aged 18 to 51) with endometriosis-associated pain will be enrolled.
Participants will receive oral relugolix once daily plus a capsule contacting low-dose estradiol/ norethindrone acetate (a combination medicine for treatment of menopause symptoms and to prevent bone loss) for up to 28 weeks. The objectives of the study are to evaluate long-term efficacy and safety through up to 52 weeks of treatment (including treatment during the parent study and this open label extension study) of relugolix co-administered with low-dose estradiol/norethindrone acetate.
Baseline procedures will be done at the same visit for this extension study that coincides with the Week 24 visit from the parent study.
Participants will undergo various tests and procedures including blood samples, urine samples, electrocardiograms, physical examinations, bone scans and eDiary/questionnaire completion.LAY SUMMARY OF RESULTS:
This multinational long-term open-label extension trial enrolled 802 women with surgically confirmed endometriosis, 84% of whom had undergone prior surgical interventions for endometriosis, with endometriosis-associated pain and high disease burden based on pain intensity, use of opioids and non-opioid pain relievers, and substantial physical limitations. To clarify total length of exposure to relugolix combination therapy through 104 weeks, patients were identified in the extension study by their original treatment group in the pivotal trials. Baseline characteristics (ie, age, race/ethnicity, pain, function, and bone mineral density) were similar across groups.Treatment with relugolix combination therapy for up to 104 weeks provided
• clinically meaningful reductions in pain associated with menstruation (dysmenorrhea) for 84.8% of women at Week 52 that was sustained at Week 104 (84.8%),
• clinically meaningful reductions in non-menstrual pelvic pain for 73.6% of women at Week 52 that was sustained at Week 104 (75.8%),
• clinically meaningful improvements in function for 83.6% of women at Week 52 and 88.6% at Week 104,
• improvement in painful intercourse (dyspareunia), with 89.1% of women reporting dyspareunia was “better” or “much better” at Week 52, and
• improvement in overall pelvic pain, with a 64.5% (Week 52) and 69.4% (Week 104) reduction in pain from baseline and an absolute score that was indicative of mild pain.Pain reduction was associated with a 77% decrease in the percentage of women using opioids. Relugolix combination therapy was generally well-tolerated with a mean decrease < 1 % in bone density that did not progress during long-term treatment. No endometrial safety concerns were identified. Resumption of menses was prompt (median time of menses return of 32 - 33 days across treatment groups) following treatment discontinuation in the majority of women, even after 104 weeks of continuous treatment with relugolix + estradiol/norethindrone acetate.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
18/WM/0238
Date of REC Opinion
19 Oct 2018
REC opinion
Further Information Favourable Opinion