Clinical trial NCT03204331: SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
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
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: 623
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 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.

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: Change From Baseline In Dyspareunia NRS Scores 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 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
measure: Change From Baseline In Opioid Use At Week 24 Or EOT
timeFrame: Baseline, Week 24
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
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Andalusia
state: Alabama
city: Washington
country: United States
facility: Washington DC
state: District of Columbia
city: Aventura
country: United States
facility: Aventura
state: Florida
city: DeLand
country: United States
facility: Deland
state: Florida
city: Hialeah
country: United States
facility: Hialeah
state: Florida
city: Hialeah
country: United States
facility: Hialeah
state: Florida
city: Margate
country: United States
facility: Margate
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Port Saint Lucie
country: United States
facility: Port St. Lucie
state: Florida
city: Tampa
country: United States
facility: Tampa
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Idaho Falls
country: United States
facility: Idaho Falls
state: Idaho
city: Park Ridge
country: United States
facility: Park Ridge
state: Illinois
city: Lafayette
country: United States
facility: Lafayette
state: Indiana
city: Covington
country: United States
facility: Covington
state: Louisiana
city: Marrero
country: United States
facility: Marrero
state: Louisiana
city: Towson
country: United States
facility: Towson
state: Maryland
city: Saginaw
country: United States
facility: Saginaw
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis
state: Missouri
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque
state: New Mexico
city: New York
country: United States
facility: New York
state: New York
city: New Bern
country: United States
facility: New Bern
state: North Carolina
city: Akron
country: United States
facility: Akron
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Franklin
country: United States
facility: Franklin
state: Ohio
city: Columbia
country: United States
facility: Columbia
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga
state: Tennessee
city: Beaumont
country: United States
facility: Beaumont
state: Texas
city: Corpus Christi
country: United States
facility: Corpus Christi
state: Texas
city: Dallas
country: United States
facility: Dallas
state: Texas
city: Fort Worth
country: United States
facility: Fort Worth
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Irving
country: United States
facility: Irving
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: Sugar Land
country: United States
facility: Sugar Land
state: Texas
city: Pleasant Grove
country: United States
facility: Pleasant Grove
state: Utah
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
city: Virginia Beach
country: United States
facility: Virginia Beach
state: Virginia
city: Sydney
country: Australia
facility: Sydney
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong
state: New South Wales
city: Sherwood
country: Australia
facility: Sherwood
state: Queensland
city: Adelaide
country: Australia
facility: Adelaide
state: South Australia
city: Nedlands
country: Australia
facility: Nedlands
state: Western Australia
city: Passo Fundo
country: Brazil
facility: Passo Fundo
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: SAO Paulo
city: São Bernardo do Campo
country: Brazil
facility: São Bernardo do Campo
state: SAO Paulo
city: São Paulo
country: Brazil
facility: São Paulo
state: SAO Paulo
city: São Paulo
country: Brazil
facility: São Paulo
state: SAO Paulo
city: São Paulo
country: Brazil
facility: São Paulo
state: SAO Paulo
city: São Paulo
country: Brazil
facility: São Paulo
state: SAO Paulo
city: São Paulo
country: Brazil
facility: São Paulo
state: SAO Paulo
city: Santiago
country: Chile
facility: Santiago
city: Santiago
country: Chile
facility: Santiago
city: Santiago
country: Chile
facility: Santiago
city: Santiago
country: Chile
facility: Santiago
city: Písek
country: Czechia
facility: Písek
state: Jihocesky KRAJ
city: Tábor
country: Czechia
facility: Tábor
state: Jihormoravsky KRAJ
city: Praha 2
country: Czechia
facility: Praha 2
state: Praha
city: České Budějovice
country: Czechia
facility: Ceské Budejovice
city: Tbilisi
country: Georgia
facility: Tbilisi
state: Borjomi
city: Monserrato
country: Italy
facility: Monserrato
state: Cagliari
city: Catanzaro
country: Italy
facility: Catanzaro
city: Napoli
country: Italy
facility: Napoli
city: Pavia
country: Italy
facility: Pavia
city: Roma
country: Italy
facility: Roma
city: Birkenhead
country: New Zealand
facility: Birkenhead
state: Auckland
city: Remuera
country: New Zealand
facility: Remuera
state: Auckland
city: Tauranga
country: New Zealand
facility: Tauranga
state: Bay Of Plenty
city: Palmerston North
country: New Zealand
facility: Palmerston North
state: Manawatu-wanganui
city: Christchurch
country: New Zealand
facility: Christchurch
city: Łódź
country: Poland
facility: Lodz
state: Lodzkie
city: Lublin
country: Poland
facility: Lublin
state: Lubelskie
city: Lublin
country: Poland
facility: Lublin
state: Lubelskie
city: Warszawa
country: Poland
facility: Warszawa
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa
state: Mazowieckie
city: Bialystok
country: Poland
facility: Bialystok
state: Podlaskie
city: Białystok
country: Poland
facility: Białystok
state: Podlaskie
city: Katowice
country: Poland
facility: Katowice
state: Slaskie
city: Poznan
country: Poland
facility: Poznan
state: Wielkopolskie
city: București
country: Romania
facility: București
state: Bucuresti
city: Brasov
country: Romania
facility: Brasov
city: Bucuresti
country: Romania
facility: Bucuresti
city: Bucuresti
country: Romania
facility: Bucuresti
city: Malmö
country: Sweden
facility: Malmö
state: Skane
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.