Endometriosis Related PainPhase 3NCT03204331
SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
A Phase 3 study testing Relugolix and Estradiol/norethindrone acetate in people with Endometriosis Related Pain, run by Myovant Sciences GmbH at 91 sites in 11 countries.
Trial summary
The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Endometriosis Related Pain
- What is being tested?
- Relugolix and Estradiol/norethindrone acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 623 participants
- Where
- 91 sitesin 11 countries
- Study dates
- 1 Nov 2017to 31 May 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form.
- Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these.
- Has a diagnosis of endometriosis and has had, within 10 years prior to signing the informed consent form, surgical or direct visualization and/or histopathologic confirmation of endometriosis, for example, during a laparoscopy or laparotomy.
- During the Run-In Period (35 to 70 days prior to treatment period) has a dysmenorrhea NRS score ≥ 4.0 on at least 2 days and
- Mean NMPP NRS score ≥ 2.5, or
- Mean NMPP NRS score ≥ 1.25 and NMPP NRS score ≥ 5.0 on ≥ 4 days.
Who cannot join
- Has a history of chronic pelvic pain that is not caused by endometriosis.
- Has any chronic pain or frequently recurring pain condition, other than endometriosis that is treated with opioids or requires analgesics for ≥ 7 days per month.
- Has had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit.
- Has a history of or currently has osteoporosis or other metabolic bone disease.
- Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.
Trial locations and contacts
91 sites in 11 countries.
91 sites in 11 countries
United States41 sites
Akron
Akron, Ohio, 44313
Albuquerque
Albuquerque, New Mexico, 87102
Andalusia
Andalusia, Alabama, 36420
Atlanta
Atlanta, Georgia, 30312
Aventura
Aventura, Florida, 33180
Beaumont
Beaumont, Texas, 77702
Chattanooga
Chattanooga, Tennessee, 37404
Columbia
Columbia, South Carolina, 29201
Columbus
Columbus, Ohio, 43231
Columbus
Columbus, Ohio, 43235
Corpus Christi
Corpus Christi, Texas, 78412
Covington
Covington, Louisiana, 70433
Dallas
Dallas, Texas, 75231
Deland
DeLand, Florida, 32720
Fort Worth
Fort Worth, Texas, 76104
Franklin
Franklin, Ohio, 45005
Hialeah
Hialeah, Florida, 33012
Hialeah
Hialeah, Florida, 33016
Houston
Houston, Texas, 77054
Idaho Falls
Idaho Falls, Idaho, 83404
Irving
Irving, Texas, 75062
Lafayette
Lafayette, Indiana, 47905
Margate
Margate, Florida, 33063
Marrero
Marrero, Louisiana, 70072
Miami
Miami, Florida, 33176
New Bern
New Bern, North Carolina, 28562
New York
New York, New York, 10038
Omaha
Omaha, Nebraska, 68124
Park Ridge
Park Ridge, Illinois, 60068
Pleasant Grove
Pleasant Grove, Utah, 84062
Port St. Lucie
Port Saint Lucie, Florida, 34952
Saginaw
Saginaw, Michigan, 48602
Salt Lake City
Salt Lake City, Utah, 84102
San Antonio
San Antonio, Texas, 78258
Spartanburg
Spartanburg, South Carolina, 29301
St. Louis
St Louis, Missouri, 63141
Sugar Land
Sugar Land, Texas, 77479
Tampa
Tampa, Florida, 33606
Towson
Towson, Maryland, 21204
Virginia Beach
Virginia Beach, Virginia, 23502
Washington DC
Washington D.C., District of Columbia, 20036
Brazil11 sites
Passo Fundo
Passo Fundo, Rio Grande do Sul, 99010-080
Porto Alegre
Porto Alegre, Rio Grande do Sul, 90430-001
Porto Alegre
Porto Alegre, Rio Grande do Sul, 90510-040
Porto Alegre
Porto Alegre, Rio Grande do Sul, 90610-000
Porto Alegre
Porto Alegre, São Paulo, 90035-903
São Bernardo do Campo
São Bernardo do Campo, São Paulo, 09715-090
São Paulo
São Paulo, São Paulo, 01317-000
São Paulo
São Paulo, São Paulo, 01323-900
São Paulo
São Paulo, São Paulo, 04023-062
São Paulo
São Paulo, São Paulo, 04266-010
São Paulo
São Paulo, São Paulo, 04708-001
Poland10 sites
Bialystok
Bialystok, Podlaskie Voivodeship, 15-224
Białystok
Bialystok, Podlaskie Voivodeship, 15-464
Katowice
Katowice, Silesian Voivodeship, 40-301
Lodz
Lodz, Łódź Voivodeship, 90-602
Lublin
Lublin, Lublin Voivodeship, 20-064
Lublin
Lublin, Lublin Voivodeship, 20-093
Poznan
Poznan, Greater Poland Voivodeship, 60-185
Warszawa
Warsaw, Masovian Voivodeship, 02-066
Warszawa
Warsaw, Masovian Voivodeship, 02-201
Warszawa
Warsaw, Masovian Voivodeship, 02-929
Australia5 sites
Adelaide
Adelaide, South Australia, 5000
Nedlands
Nedlands, Western Australia, 6009
Sherwood
Sherwood, Queensland, 4075
Sydney
Sydney, New South Wales, 2000
Wollongong
Wollongong, New South Wales, 2522
Italy5 sites
Catanzaro
Catanzaro, 88100
Monserrato
Monserrato, Cagliari, 09042
Napoli
Naples, 80131
Pavia
Pavia, 27100
Roma
Roma, 00168
New Zealand5 sites
Birkenhead
Birkenhead, Auckland, 0626
Christchurch
Christchurch, 8013
Palmerston North
Palmerston North, Manawatu-Wanganui, 4442
Remuera
Remuera, Auckland, 1050
Tauranga
Tauranga, Bay of Plenty, 3112
Chile4 sites
Santiago
Santiago, 7510186
Santiago
Santiago, 8320165
Santiago
Santiago, 8360160
Santiago
Santiago, 8880465
Czechia4 sites
Ceské Budejovice
České Budějovice, 370 01
Písek
Písek, South Bohemian Region, 39701
Praha 2
Prague, Prague, 128 08
Tábor
Tábor, Jihormoravsky KRAJ, 390 03
Romania4 sites
Brasov
Brasov, 500091
București
Bucharest, Bucharest, 20475
Bucuresti
Bucharest, 012071
Bucuresti
Bucharest, 022441
About this study
Official title: SPIRIT 2: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Endometriosis-Associated Pain
The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.
Read the detailed description
This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral, once-daily relugolix (40 mg) co-administered with either 12 or 24 weeks of low-dose E2 (1.0 mg) and NETA (0.5 mg), compared with placebo.
Approximately 600 women with endometriosis-associated pain were enrolled and randomized 1:1:1 to Group A - relugolix plus low-dose hormonal add-back therapy, Group B - relugolix monotherapy for 12 weeks followed by co-administration with low-dose hormonal add-back therapy, or Group C - placebo (N = 200 per group).
Eligible participants were randomized on Baseline Day 1 to Treatment Group A, B, or C, in the double-blind period.
Eligible participants, including those randomized to placebo, were offered the opportunity to enroll in an 80-week open label extension study where participants received relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a Follow-Up visit approximately 30 days after the participant's last dose of study drug.
- Conditions
- Endometriosis Related Pain
- Being tested
- Relugolix, Estradiol/norethindrone acetate, Estradiol/norethindrone acetate placebo, Relugolix placebo
- Keywords
- Endometriosis, Pain, Dysmenorrhea
- Medical subject headings
- Endometriosis, Pain, Dysmenorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RelugolixDrug
Also called TAK-385, MVT-601
Relugolix 40-mg tablet administered orally once daily.
Estradiol/norethindrone acetateDrug
Also called E2/NETA
Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.
Estradiol/norethindrone acetate placeboDrug
E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor.
Relugolix placeboDrug
Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.
| Study group | Role | What they receive |
|---|---|---|
| Relugolix plus E2/NETA (Group A) | Experimental | Relugolix co-administered with E2/NETA for 24 weeks. Receives: Drug: Relugolix; Drug: Estradiol/norethindrone acetate |
| Relugolix plus Delayed E2/NETA (Group B) | Experimental | Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks. Receives: Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Estradiol/norethindrone acetate placebo |
| Placebo (Group C) | Placebo comparator | Relugolix placebo co-administered with E2/NETA placebo for 24 weeks. Receives: Drug: Estradiol/norethindrone acetate placebo; Drug: Relugolix placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)
Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Measured: Week 24 or EOT
Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Measured: Week 24 or EOT
Secondary outcomes (43)
Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24
Assessed using the Pain Domain of the EHP-30 questionnaire.
Measured: Baseline, Week 24
Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Change From Baseline In NMPP NRS Score At Week 24 Or EOT
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT
Assessed using an NRS score (11-point scale) for dyspareunia recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT
Assessed based on usage of protocol-specified opioids for endometriosis-associated pain recorded daily in an e-Diary.
Measured: Week 24 or EOT
Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT
Assessed based on usage of protocol-specified analgesic for endometriosis-associated pain recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24
Assessed using the pain domain of the EHP-30 questionnaire.
Measured: Baseline to Week 24
Dysmenorrhea Responder Rate By Month
The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Measured: Baseline to Week 24
NMPP Responder Rate By Month
The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Measured: Baseline to Week 24
Change In Dysmenorrhea NRS Score By Month
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline to Week 24
Change In NMPP NRS Score By Month
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline to Week 24
Change In Overall Pelvic Pain NRS Score By Month
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline to Week 24
Change In Dyspareunia NRS Score By Month
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Measured: Baseline to Week 24
Change From Baseline In Ibuprofen Use At Week 24 Or EOT
Assessed using ibuprofen pill counts for endometriosis-associated pain recorded daily in an e-Diary.
Measured: Baseline, Week 24
Change From Baseline In Opioid Use At Week 24 Or EOT
Assessed using opioid pill counts for endometriosis-associated pain recorded daily in an e-Diary.
Measured: Baseline, Week 24
Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT
Assessed using the subject modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT
Assessed using the subject modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT
Assessed using the subject modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an e-Diary.
Measured: Baseline, Week 24 or EOT
Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24
The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle.
Measured: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At Week 24
The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle.
Measured: Week 24
Change From Baseline In PGA For NMPP Symptom Severity At Week 24
The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.
Measured: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24
The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.
Measured: Week 24
Change From Baseline In PGA For Pain Severity At Week 24
The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Measured: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24
The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Measured: Week 24
Change From Baseline In PGA For Function At Week 24
The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Measured: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24
The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Measured: Week 24
Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24
The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.
Measured: Week 24
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24
The PGIC for NMPP is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.
Measured: Week 24
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24
The PGIC for dyspareunia is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during sexual intercourse.
Measured: Week 24
Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24
Assessed using the non-pain domains (Control and Powerlessness, Social Support, Emotional Well-Being, and Self-Image) of the EHP-30 questionnaire.
Measured: Baseline, Week 24
Change From Baseline In The EHP-30 Scale Total Score At Week 24
Assessed using the total score of the EHP-30 questionnaire.
Measured: Baseline, Week 24
Change From Baseline In The EHP Work Domain Score At Week 24
The EHP Work domain is a 5-item questionnaire that assesses impact of pain on ability to work.
Measured: Baseline, Week 24
Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.
Measured: Baseline, Week 24
Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.
Measured: Baseline, Week 24
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Measured: Week 24 or EOT
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Measured: Week 24 or EOT
Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA
Assessed using the Pain Domain of the EHP-30 questionnaire.
Measured: Baseline, Week 24
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA
Assessed using the pain domain of the EHP-30 questionnaire.
Measured: Baseline to Week 24
Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12
Assessed by dual-energy X-ray absorptiometry (DXA) scan.
Measured: Baseline, Week 12
Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24
Assessed by DXA scan.
Measured: Baseline, Week 24
Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B
Measured: Week 12
Change From Baseline In Serum Concentrations Of Luteinizing Hormone, Follicle Stimulating Hormone, Estradiol, And Progesterone
Blood samples will be collected from participants for hormonal measurements.
Measured: Baseline, Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start1 Nov 2017
- Primary completion1 Apr 2020
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Endometriosis Related PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 623 participants (actual)
Sponsor and investigators
- Lead sponsor
- Myovant Sciences GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Myovant Medical Monitor, Study director, Myovant Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03204331
- Sponsor's protocol ID
- MVT-601-3102
- Other IDs
- 2017-001632-19, 2017
- Status last verified
- Jun 2021
- First submitted
- 27 Jun 2017
- Last updated
- 28 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Giudice LC, As-Sanie S, Arjona Ferreira JC, Becker CM, Abrao MS, Lessey BA, Dynowski K, Wilk K, Li Y, Mathur V, Wagman RB, Johnson NP. A Plain Language Summary to learn about relugolix combination therapy for the treatment of pain associated with endometriosis. Pain Manag. 2023 Nov;13(11):631-640. doi: 10.2217/pmt-2023-0052. Epub 2023 Nov 20.
PubMed 37982388Hunsche E, Gauthier M, Witherspoon B, Rakov V, Agarwal SK. Endometriosis Symptoms and Their Impacts on the Daily Lives of US Women: Results from an Interview Study. Int J Womens Health. 2023 Jun 1;15:893-904. doi: 10.2147/IJWH.S409733. eCollection 2023.
PubMed 37283994Giudice LC, As-Sanie S, Arjona Ferreira JC, Becker CM, Abrao MS, Lessey BA, Brown E, Dynowski K, Wilk K, Li Y, Mathur V, Warsi QA, Wagman RB, Johnson NP. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022 Jun 18;399(10343):2267-2279. doi: 10.1016/S0140-6736(22)00622-5.
PubMed 35717987
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SPIRIT 2: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Endometriosis-Associated Pain
- ClinicalTrials.gov ID
- NCT03204331
- Acronym / sponsor ID
- MVT-601-3102
- Conditions
- Endometriosis Related Pain
- Keywords
- Endometriosis, Pain, Dysmenorrhea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 623 participants (actual)
- Lead sponsor
- Myovant Sciences GmbHIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 1 Apr 2020 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 2 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.
Detailed description
This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral, once-daily relugolix (40 mg) co-administered with either 12 or 24 weeks of low-dose E2 (1.0 mg) and NETA (0.5 mg), compared with placebo.
Approximately 600 women with endometriosis-associated pain were enrolled and randomized 1:1:1 to Group A - relugolix plus low-dose hormonal add-back therapy, Group B - relugolix monotherapy for 12 weeks followed by co-administration with low-dose hormonal add-back therapy, or Group C - placebo (N = 200 per group).
Eligible participants were randomized on Baseline Day 1 to Treatment Group A, B, or C, in the double-blind period.
Eligible participants, including those randomized to placebo, were offered the opportunity to enroll in an 80-week open label extension study where participants received relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a Follow-Up visit approximately 30 days after the participant's last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Relugolix plus E2/NETA (Group A) | Experimental | Drug: Relugolix, Drug: Estradiol/norethindrone acetateRelugolix co-administered with E2/NETA for 24 weeks. |
| Relugolix plus Delayed E2/NETA (Group B) | Experimental | Drug: Relugolix, Drug: Estradiol/norethindrone acetate, Drug: Estradiol/norethindrone acetate placeboRelugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks. |
| Placebo (Group C) | Placebo comparator | Drug: Estradiol/norethindrone acetate placebo, Drug: Relugolix placeboRelugolix placebo co-administered with E2/NETA placebo for 24 weeks. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form.
- Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these.
- Has a diagnosis of endometriosis and has had, within 10 years prior to signing the informed consent form, surgical or direct visualization and/or histopathologic confirmation of endometriosis, for example, during a laparoscopy or laparotomy.
- During the Run-In Period (35 to 70 days prior to treatment period) has a dysmenorrhea NRS score ≥ 4.0 on at least 2 days and
Key exclusion criteria (5 listed)
- Has a history of chronic pelvic pain that is not caused by endometriosis.
- Has any chronic pain or frequently recurring pain condition, other than endometriosis that is treated with opioids or requires analgesics for ≥ 7 days per month.
- Has had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit.
- Has a history of or currently has osteoporosis or other metabolic bone disease.
- Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RelugolixAlso: TAK-385, MVT-601Relugolix 40-mg tablet administered orally once daily. | Drug | Relugolix plus Delayed E2/NETA (Group B), Relugolix plus E2/NETA (Group A) |
| Estradiol/norethindrone acetateAlso: E2/NETACapsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily. | Drug | Relugolix plus Delayed E2/NETA (Group B), Relugolix plus E2/NETA (Group A) |
| Estradiol/norethindrone acetate placeboE2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor. | Drug | Placebo (Group C), Relugolix plus Delayed E2/NETA (Group B) |
| Relugolix placeboRelugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor. | Drug | Placebo (Group C) |
Primary outcome
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)
Time frame: Week 24 or EOT
Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT
Time frame: Week 24 or EOT
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
43 secondary outcomes
Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24
Time frame: Baseline, Week 24
Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Change From Baseline In NMPP NRS Score At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT
Time frame: Week 24 or EOT
Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24
Time frame: Baseline to Week 24
Dysmenorrhea Responder Rate By Month
Time frame: Baseline to Week 24
NMPP Responder Rate By Month
Time frame: Baseline to Week 24
Change In Dysmenorrhea NRS Score By Month
Time frame: Baseline to Week 24
Change In NMPP NRS Score By Month
Time frame: Baseline to Week 24
Change In Overall Pelvic Pain NRS Score By Month
Time frame: Baseline to Week 24
Change In Dyspareunia NRS Score By Month
Time frame: Baseline to Week 24
Change From Baseline In Ibuprofen Use At Week 24 Or EOT
Time frame: Baseline, Week 24
Change From Baseline In Opioid Use At Week 24 Or EOT
Time frame: Baseline, Week 24
Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT
Time frame: Baseline, Week 24 or EOT
Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24
Time frame: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At Week 24
Time frame: Week 24
Change From Baseline In PGA For NMPP Symptom Severity At Week 24
Time frame: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24
Time frame: Week 24
Change From Baseline In PGA For Pain Severity At Week 24
Time frame: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24
Time frame: Week 24
Change From Baseline In PGA For Function At Week 24
Time frame: Baseline, Week 24
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24
Time frame: Week 24
Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24
Time frame: Week 24
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24
Time frame: Week 24
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24
Time frame: Week 24
Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24
Time frame: Baseline, Week 24
Change From Baseline In The EHP-30 Scale Total Score At Week 24
Time frame: Baseline, Week 24
Change From Baseline In The EHP Work Domain Score At Week 24
Time frame: Baseline, Week 24
Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24
Time frame: Baseline, Week 24
Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24
Time frame: Baseline, Week 24
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA
Time frame: Week 24 or EOT
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA
Time frame: Week 24 or EOT
Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA
Time frame: Baseline, Week 24
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA
Time frame: Baseline to Week 24
Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12
Time frame: Baseline, Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2021.
- Derived from this study: PubMed 37982388Giudice LC, As-Sanie S, Arjona Ferreira JC, Becker CM, Abrao MS, Lessey BA, Dynowski K, Wilk K, Li Y, Mathur V, Wagman RB, Johnson NP. A Plain Language Summary to learn about relugolix combination therapy for the treatment of pain associated with endometriosis. Pain Manag. 2023 Nov;13(11):631-640. doi: 10.2217/pmt-2023-0052. Epub 2023 Nov 20.
- Derived from this study: PubMed 37283994Hunsche E, Gauthier M, Witherspoon B, Rakov V, Agarwal SK. Endometriosis Symptoms and Their Impacts on the Daily Lives of US Women: Results from an Interview Study. Int J Womens Health. 2023 Jun 1;15:893-904. doi: 10.2147/IJWH.S409733. eCollection 2023.
- Derived from this study: PubMed 35717987Giudice LC, As-Sanie S, Arjona Ferreira JC, Becker CM, Abrao MS, Lessey BA, Brown E, Dynowski K, Wilk K, Li Y, Mathur V, Warsi QA, Wagman RB, Johnson NP. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022 Jun 18;399(10343):2267-2279. doi: 10.1016/S0140-6736(22)00622-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Myovant Medical Monitor study director
Myovant Sciences
91 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Relugolix and Estradiol/norethindrone acetate in people with Endometriosis Related Pain, run by Myovant Sciences GmbH at 91 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 91 sites in United States, Brazil, Poland, Australia, Italy and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT) (time frame: Week 24 or EOT). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03204331, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2021.