SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

Endometriosis Related Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03204331
• Other study ID #: MVT-601-3102
• Secondary ID: 2017-001632-19
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2017
• Est. completion date: May 31, 2021

Study information

• Verified date: June 2021
• Source: Myovant Sciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 623
• Est. completion date: May 31, 2021
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Key Inclusion Criteria:

1. Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form.

2. Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these.

3. 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.

4. 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

1. Mean NMPP NRS score = 2.5, or

2. Mean NMPP NRS score = 1.25 and NMPP NRS score = 5.0 on = 4 days.

Key Exclusion Criteria:

1. Has a history of chronic pelvic pain that is not caused by endometriosis.

2. 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.

3. Has had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit.

4. Has a history of or currently has osteoporosis or other metabolic bone disease.

5. Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.

Related Conditions & MeSH terms

• Endometriosis
• Endometriosis Related Pain

Intervention

Drug:
• Relugolix
Relugolix 40-mg tablet administered orally once daily.
• Estradiol/norethindrone acetate
Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.
• Estradiol/norethindrone acetate placebo
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 placebo
Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Locations

Country	Name	City	State
Australia	Adelaide	Adelaide	South Australia
Australia	Nedlands	Nedlands	Western Australia
Australia	Sherwood	Sherwood	Queensland
Australia	Sydney	Sydney	New South Wales
Australia	Wollongong	Wollongong	New South Wales
Brazil	Passo Fundo	Passo Fundo	RIO Grande DO SUL
Brazil	Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Porto Alegre	Porto Alegre	RIO Grande DO SUL
Brazil	Porto Alegre	Porto Alegre	RIO Grande DO SUL
Brazil	Porto Alegre	Porto Alegre	SAO Paulo
Brazil	São Bernardo do Campo	São Bernardo do Campo	SAO Paulo
Brazil	São Paulo	São Paulo	SAO Paulo
Brazil	São Paulo	São Paulo	SAO Paulo
Brazil	São Paulo	São Paulo	SAO Paulo
Brazil	São Paulo	São Paulo	SAO Paulo
Brazil	São Paulo	São Paulo	SAO Paulo
Chile	Santiago	Santiago
Chile	Santiago	Santiago
Chile	Santiago	Santiago
Chile	Santiago	Santiago
Czechia	Ceské Budejovice	Ceské Budejovice
Czechia	Písek	Písek	Jihocesky KRAJ
Czechia	Praha 2	Praha 2	Praha
Czechia	Tábor	Tábor	Jihormoravsky KRAJ
Georgia	Tbilisi	Tbilisi	Borjomi
Italy	Catanzaro	Catanzaro
Italy	Monserrato	Monserrato	Cagliari
Italy	Napoli	Napoli
Italy	Pavia	Pavia
Italy	Roma	Roma
New Zealand	Birkenhead	Birkenhead	Auckland
New Zealand	Christchurch	Christchurch
New Zealand	Palmerston North	Palmerston North	Manawatu-wanganui
New Zealand	Remuera	Remuera	Auckland
New Zealand	Tauranga	Tauranga	Bay Of Plenty
Poland	Bialystok	Bialystok	Podlaskie
Poland	Bialystok	Bialystok	Podlaskie
Poland	Katowice	Katowice	Slaskie
Poland	Lodz	Lódz	Lodzkie
Poland	Lublin	Lublin	Lubelskie
Poland	Lublin	Lublin	Lubelskie
Poland	Poznan	Poznan	Wielkopolskie
Poland	Warszawa	Warszawa	Mazowieckie
Poland	Warszawa	Warszawa	Mazowieckie
Poland	Warszawa	Warszawa	Mazowieckie
Romania	Brasov	Brasov
Romania	Bucure?ti	Bucure?ti	Bucuresti
Romania	Bucuresti	Bucuresti
Romania	Bucuresti	Bucuresti
Sweden	Malmö	Malmö	Skane
United States	Akron	Akron	Ohio
United States	Albuquerque	Albuquerque	New Mexico
United States	Andalusia	Andalusia	Alabama
United States	Atlanta	Atlanta	Georgia
United States	Aventura	Aventura	Florida
United States	Beaumont	Beaumont	Texas
United States	Chattanooga	Chattanooga	Tennessee
United States	Columbia	Columbia	South Carolina
United States	Columbus	Columbus	Ohio
United States	Columbus	Columbus	Ohio
United States	Corpus Christi	Corpus Christi	Texas
United States	Covington	Covington	Louisiana
United States	Dallas	Dallas	Texas
United States	Deland	DeLand	Florida
United States	Fort Worth	Fort Worth	Texas
United States	Franklin	Franklin	Ohio
United States	Hialeah	Hialeah	Florida
United States	Hialeah	Hialeah	Florida
United States	Houston	Houston	Texas
United States	Idaho Falls	Idaho Falls	Idaho
United States	Irving	Irving	Texas
United States	Lafayette	Lafayette	Indiana
United States	Margate	Margate	Florida
United States	Marrero	Marrero	Louisiana
United States	Miami	Miami	Florida
United States	New Bern	New Bern	North Carolina
United States	New York	New York	New York
United States	Omaha	Omaha	Nebraska
United States	Park Ridge	Park Ridge	Illinois
United States	Pleasant Grove	Pleasant Grove	Utah
United States	Port St. Lucie	Port Saint Lucie	Florida
United States	Saginaw	Saginaw	Michigan
United States	St. Louis	Saint Louis	Missouri
United States	Salt Lake City	Salt Lake City	Utah
United States	San Antonio	San Antonio	Texas
United States	Spartanburg	Spartanburg	South Carolina
United States	Sugar Land	Sugar Land	Texas
United States	Tampa	Tampa	Florida
United States	Towson	Towson	Maryland
United States	Virginia Beach	Virginia Beach	Virginia
United States	Washington DC	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Myovant Sciences GmbH

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Chile,  Czechia,  Georgia,  Italy,  New Zealand,  Poland,  Romania,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 24 or EOT
Primary	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.	Week 24 or EOT
Secondary	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.	Baseline, Week 24
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Week 24 or EOT
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline to Week 24
Secondary	Dysmenorrhea Responder Rate By Month	The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.	Baseline to Week 24
Secondary	NMPP Responder Rate By Month	The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.	Baseline to Week 24
Secondary	Change In Dysmenorrhea NRS Score By Month	Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.	Baseline to Week 24
Secondary	Change In NMPP NRS Score By Month	Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	Change In Dyspareunia NRS Score By Month	Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.	Baseline to Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline, Week 24 or EOT
Secondary	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.	Baseline, Week 24
Secondary	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.	Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Week 24
Secondary	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.	Week 24
Secondary	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.	Week 24
Secondary	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.	Week 24
Secondary	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.	Baseline, Week 24
Secondary	Change From Baseline In The EHP-30 Scale Total Score At Week 24	Assessed using the total score of the EHP-30 questionnaire.	Baseline, Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Baseline, Week 24
Secondary	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.	Week 24 or EOT
Secondary	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.	Week 24 or EOT
Secondary	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.	Baseline, Week 24
Secondary	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.	Baseline to Week 24
Secondary	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.	Baseline, Week 12
Secondary	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.	Baseline, Week 24
Secondary	Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B		Week 12
Secondary	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.	Baseline, Week 24