Clinical trial NCT03204318: SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
Official title: SPIRIT 1: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometriosis Related Pain
Keywords: Endometriosis
Pain
Dysmenorrhea
Lead sponsor: Myovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2017-07-02
Enrollment: 638
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 will be 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)
timeFrame: Week 24 or EOT
measure: Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT
timeFrame: Week 24 or EOT
Secondary outcomes:
measure: Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In NMPP NRS Score At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT
timeFrame: Week 24 or EOT
measure: Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24
timeFrame: Baseline to Week 24
measure: Dysmenorrhea Responder Rate By Month
timeFrame: Baseline to Week 24
measure: NMPP Responder Rate By Month
timeFrame: Baseline to Week 24
measure: Change In Dysmenorrhea NRS Score By Month
timeFrame: Baseline to Week 24
measure: Change In NMPP NRS Score By Month
timeFrame: Baseline to Week 24
measure: Change In Overall Pelvic Pain NRS Score By Month
timeFrame: Baseline to Week 24
measure: Change In Dyspareunia NRS Score By Month
timeFrame: Baseline to Week 24
measure: Change From Baseline In Ibuprofen Use At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In Opioid Use At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT
timeFrame: Baseline, Week 24 or EOT
measure: Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24
timeFrame: Baseline, Week 24
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At Week 24
timeFrame: Week 24
measure: Change From Baseline In PGA For NMPP Symptom Severity At Week 24
timeFrame: Baseline, Week 24
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24
timeFrame: Week 24
measure: Change From Baseline In PGA For Pain Severity At Week 24
timeFrame: Baseline, Week 24
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24
timeFrame: Week 24
measure: Change From Baseline In PGA For Function At Week 24
timeFrame: Baseline, Week 24
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24
timeFrame: Week 24
measure: Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24
timeFrame: Week 24
measure: Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24
timeFrame: Week 24
measure: Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24
timeFrame: Week 24
measure: Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In The EHP-30 Scale Total Score At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In The EHP Work Domain Score At Week 24
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24
timeFrame: Baseline, Week 24
measure: Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA
timeFrame: Week 24 or EOT
measure: Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA
timeFrame: Week 24 or EOT
measure: Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline to Week 24
measure: Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12
timeFrame: Baseline, Week 12
measure: Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24
timeFrame: Baseline, Week 24
measure: Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B
timeFrame: Week 12
measure: Change From Baseline In Serum Concentrations Of Luteinizing Hormone, Follicle Stimulating Hormone, Estradiol, And Progesterone
timeFrame: Baseline, Week 24
measure: Pre-dose Relugolix Plasma Concentrations
timeFrame: Week 4
measure: Endometrial Biopsy At Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Dothan
state: Alabama
city: Mesa
country: United States
facility: Mesa
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Canoga Park
country: United States
facility: Canoga Park
state: California
city: Long Beach
country: United States
facility: Long Beach
state: California
city: San Diego
country: United States
facility: San Diego
state: California
city: Greenwood Village
country: United States
facility: Greenwood Village
state: Colorado
city: Fort Myers
country: United States
facility: Fort Myers
state: Florida
city: Loxahatchee Groves
country: United States
facility: Loxahatchee
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Orlando
country: United States
facility: Orlando
state: Florida
city: Oviedo
country: United States
facility: Oviedo
state: Florida
city: Plantation
country: United States
facility: Plantation
state: Florida
city: Sarasota
country: United States
facility: Sarasota
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Augusta
country: United States
facility: Augusta
state: Georgia
city: Norcross
country: United States
facility: Norcross
state: Georgia
city: Idaho Falls
country: United States
facility: Idaho Falls
state: Idaho
city: Oak Brook
country: United States
facility: Oakbrook
state: Illinois
city: Shawnee Mission
country: United States
facility: Shawnee
state: Kansas
city: New Orleans
country: United States
facility: New Orleans
state: Louisiana
city: Jefferson City
country: United States
facility: Jefferson City
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas
state: Nevada
city: Port Jefferson
country: United States
facility: Port Jefferson
state: New York
city: Durham
country: United States
facility: Durham
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Winston-Salem
country: United States
facility: Winston Salem
state: North Carolina
city: Englewood
country: United States
facility: Englewood
state: Ohio
city: Hershey
country: United States
facility: Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Memphis
state: Tennessee
city: Murfreesboro
country: United States
facility: Murfreesboro
state: Tennessee
city: Austin
country: United States
facility: Austin
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Webster
country: United States
facility: Webster
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
city: Norfolk
country: United States
facility: Norfolk
state: Virginia
city: Richmond
country: United States
facility: Richmond
state: Virginia
city: Seattle
country: United States
facility: Seattle
state: Washington
city: Ciudad de Buenos Aires
country: Argentina
facility: Ciudad de Buenos Aires
state: Buenos Aires
city: San Isidro
country: Argentina
facility: San Isidro
state: Buenos Aires
city: Rosario
country: Argentina
facility: Rosario
state: Santa Fe
city: Córdoba
country: Argentina
facility: Córdoba
city: Leuven
country: Belgium
facility: Leuven
state: Flemish Brabant
city: La Louvière
country: Belgium
facility: La Louvière
state: Hainaut
city: Gent
country: Belgium
facility: Gent
state: Oost-vlaanderen
city: Brussels
country: Belgium
facility: Brussels
city: Sofia
country: Bulgaria
facility: Sofia
state: Sofiya
city: Sofia
country: Bulgaria
facility: Sofia
state: Sofiya
city: Sofia
country: Bulgaria
facility: Sofia
state: Sofiya
city: Blagoevgrad
country: Bulgaria
facility: Blagoevgrad
city: Pleven
country: Bulgaria
facility: Pleven
city: Sofia
country: Bulgaria
facility: Sofia
city: Sofia
country: Bulgaria
facility: Sofia
city: Stara Zagora
country: Bulgaria
facility: Stara Zagora
city: Varna
country: Bulgaria
facility: Varna
city: Red Deer
country: Canada
facility: Red Deer
state: Alberta
city: Waterloo
country: Canada
facility: Waterloo
state: Ontario
city: Victoriaville
country: Canada
facility: Victoriaville
state: Quebec
city: Praha 10
country: Czechia
facility: Praha 10
state: Praha
city: Náchod
country: Czechia
facility: Nachod
city: Olomouc
country: Czechia
facility: Olomouc
city: Praha 8 - Libeň
country: Czechia
facility: Praha 8 - Libeň
city: Vodňany
country: Czechia
facility: Vodnany
city: Vysoké Mýto
country: Czechia
facility: Vysoké Mýto
city: Kuopio
country: Finland
facility: Kuopio
state: Eastern Finland
city: Helsinki
country: Finland
facility: Helsinki
state: Southern Finland
city: Oulu
country: Finland
facility: Oulu
city: Kecskemét
country: Hungary
facility: Kecskemét
state: Bacs-kiskun
city: Pécs
country: Hungary
facility: Pécs
state: Baranya
city: Békéscsaba
country: Hungary
facility: Békéscsaba
state: Bekes
city: Gyula
country: Hungary
facility: Gyula
state: Bekes
city: Szeged
country: Hungary
facility: Szeged
state: Csongrad
city: Debrecen
country: Hungary
facility: Debrecen
state: Hajdu-bihar
city: Debrecen
country: Hungary
facility: Debrecen
state: Hajdu-bihar
city: Debrecen
country: Hungary
facility: Debrecen
state: Hajdu-Bihar
city: Nyíregyháza
country: Hungary
facility: Nyíregyháza
state: Szabolcs-szatmar-bereg
city: Budapest
country: Hungary
facility: Budapest
city: Budapest
country: Hungary
facility: Budapest
city: Budapest
country: Hungary
facility: Budapest
city: Lódz
country: Poland
facility: Lódz
state: Lodzkie
city: Lublin
country: Poland
facility: Lublin
state: Lubelskie
city: Lublin
country: Poland
facility: Lublin
state: Lubelskie
city: Lublin
country: Poland
facility: Lublin
state: Lubelskie
city: Kraków
country: Poland
facility: Kraków
state: Malopolskie
city: Warszawa
country: Poland
facility: Warszawa
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa
state: Mazowieckie
city: Białystok
country: Poland
facility: Białystok
state: Podlaskie
city: Katowice
country: Poland
facility: Katowice
state: Slaskie
city: Katowice
country: Poland
facility: Katowice
state: Slaskie
city: Poznań
country: Poland
facility: Poznań
state: Wielkopolskie
city: Skórzewo
country: Poland
facility: Skórzewo
state: Wielkopolskie
city: Szczecin
country: Poland
facility: Szczecin
state: Zachodniopomorskie
city: Almada
country: Portugal
facility: Almada
state: Lisboa
city: Coimbra
country: Portugal
facility: Coimbra
city: Covilhã
country: Portugal
facility: Covilhã
city: Lisbon
country: Portugal
facility: Lisbon
city: Porto
country: Portugal
facility: Porto
city: Port Elizabeth
country: South Africa
facility: Port Elizabeth
state: Eastern Cape
city: Centurion
country: South Africa
facility: Centurion
state: Gauteng
city: Roodepoort
country: South Africa
facility: Roodepoort
state: Gauteng
city: Durban
country: South Africa
facility: Durban
state: Kwazulu-natal
city: Cape Town
country: South Africa
facility: Cape Town
state: Western Cape
city: Madrid
country: Spain
facility: Madrid
city: Valencia
country: Spain
facility: Valencia
city: Kyiv
country: Ukraine
facility: Kyiv
state: Kiev City
city: Kyiv
country: Ukraine
facility: Kyiv
state: Kiev City
city: Kyiv
country: Ukraine
facility: Kyiv
state: Kiev
city: Chernivtsi
country: Ukraine
facility: Chernivtsi
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk
city: Kharkiv
country: Ukraine
facility: Kharkiv
city: Kiev
country: Ukraine
facility: Kiev
city: Kiev
country: Ukraine
facility: Kiev
city: Kiev
country: Ukraine
facility: Kiev
city: Vinnytsya
country: Ukraine
facility: Vinnytsya
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya
Study officials:
affiliation: Myovant Sciences
name: Myovant Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Giudice 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.
citation: Rolla E. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res. 2019 Apr 23;8:F1000 Faculty Rev-529. doi: 10.12688/f1000research.14817.1. eCollection 2019.