Clinical trial NCT03654274: SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometriosis
Keywords: Endometriosis
Dysmenorrhea
Pain
Dyspareunia
Pelvic Pain
Lead sponsor: Myovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2018-08-31
Enrollment: 802
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 51
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label extension
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long-term efficacy and safety of relugolix 40 milligram (mg) once daily co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) for up to 104 weeks on endometriosis-associated pain in participants who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3101 or MVT-601-3102).

Detailed description: This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that will enroll eligible participants who have completed their participation in one of the phase 3 randomized, double-blind, placebo-controlled parent studies, MVT-601-3101 (SPIRIT 1 - NCT03204318) or MVT-601-3102 (SPIRIT 2 - NCT03204331). All participants will receive relugolix 40 mg orally once daily co-administered with low-dose E2 (1.0 mg) and NETA (0.5 mg) for 80 weeks.

Approximately 800 women with endometriosis-associated pain will be enrolled, after having completed a 24-week treatment period in one of the parent studies. The objectives of the study are to evaluate long-term efficacy and safety through up to 104 weeks of treatment (including treatment during the parent study) of relugolix co-administered with low-dose E2/NETA.

Baseline procedures for this extension study will be performed on the same day as the Week 24 Visit of the parent study. This visit, referred to as the "Week 24/Baseline Visit, will be defined as the date of completion of the last Week 24 procedure in the parent study. Participants will have received their last dose of study drug in the parent study on the day prior to the Week 24/Baseline Visit and will receive their first dose of study drug for this extension study in the clinic after the participant is determined to be eligible for this extension study and has provided informed consent to participate. The administration of the first dose of study drug for MVT-601-3103 will define enrollment into this study. Study participants will then take the open-label study treatment orally, once daily for 80 weeks.

Eligibility criteria: Key Inclusion Criteria:

1. Completed 24 weeks of study drug treatment and study participation in either parent study, MVT-601-3101 or MVT-601-3102.
2. Is not expected to undergo gynecological surgery or other surgical procedures for treatment of endometriosis (including ablation, shaving, or excision) during the study, including during the Follow-Up Period, and the participant does not desire such treatment during this time frame.
3. Has agreed to continue to use only study-specified analgesic medications during the study and is not known to be intolerant to these.

Key Exclusion Criteria:

1. Has had a surgical procedure for treatment for endometriosis at any time during the parent study (MVT-601-3101 or MVT-601-3102).
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 a Z-score \< -2.0 or has a ≥ 7% decrease in bone mineral density from the parent study Baseline at lumbar spine, total hip, or femoral neck based on the parent study Week 24 DXA assessment of bone mineral density.
4. Has any contraindication to treatment with low-dose E2 and NETA, including:

   1. Known, suspected, or history of breast cancer;
   2. Known or suspected estrogen-dependent neoplasia;
   3. Active deep vein thrombosis or pulmonary embolism, or history of these conditions prior to the Week 24/Baseline visit;
   4. History of or active arterial thromboembolic disease, including stroke and myocardial infarction;
   5. Known anaphylactic reaction or angioedema or hypersensitivity to E2 or NETA;
   6. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilia disorders, including Factor V Leiden;
   7. Migraine with aura;
   8. History of porphyria.
5. Had any of the following clinical laboratory abnormalities at the parent study Week 20 visit or, if available, any subsequent visit in one of the parent studies (MVT-601-3101 or MVT-601-3102):

   1. Alanine aminotransferase or aspartate aminotransferase \> 2.0 times the upper limit of normal (ULN); or
   2. Bilirubin (total bilirubin) \> 1.5 x ULN (or \> 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome).

Primary outcomes:
measure: Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 52
timeFrame: Week 52
measure: Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 52
timeFrame: Week 52
measure: Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 104
timeFrame: Week 104
Secondary outcomes:
measure: Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 52
timeFrame: Week 52
measure: Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 104
timeFrame: Week 104
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 104
timeFrame: Week 104
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Not Using Opioids For Endometriosis-associated Pain At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Not Using Analgesics For Endometriosis-associated Pain At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 104
timeFrame: Week 104
measure: Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 104
timeFrame: Week 104
measure: Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 104
timeFrame: Week 104
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52
timeFrame: Week 52
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104
timeFrame: Week 104
measure: Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 104
timeFrame: Week 104
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52
timeFrame: Week 52
measure: Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104
timeFrame: Week 104
measure: Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104
timeFrame: Week 104
measure: Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 52
timeFrame: Week 52
measure: Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 104
timeFrame: Week 104
measure: Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 52
timeFrame: Week 52
measure: Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 104
timeFrame: Week 104
measure: Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52
timeFrame: Week 52
measure: Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104
timeFrame: Week 104
measure: Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 52
timeFrame: Week 52
measure: Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 104
timeFrame: Week 104
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Andalusia
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Tucson
country: United States
facility: Tuscon
state: Arizona
city: Canoga Park
country: United States
facility: Canoga Park
state: California
city: Los Angeles
country: United States
facility: Los Angeles
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: Washington
country: United States
facility: Washington
state: District of Columbia
city: Aventura
country: United States
facility: Aventura
state: Florida
city: Fort Myers
country: United States
facility: Fort Myers
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: Miami
country: United States
facility: Miami
state: Florida
city: Sarasota
country: United States
facility: Sarasota
state: Florida
city: Tampa
country: United States
facility: Tampa
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
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: Oakbrook Terrace
country: United States
facility: Oakbrook
state: Illinois
city: Park Ridge
country: United States
facility: Park Ridge
state: Illinois
city: Shawnee Mission
country: United States
facility: Shawnee
state: Kansas
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: Jefferson City
country: United States
facility: Jefferson City
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis
state: Missouri
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas
state: Nevada
city: Durham
country: United States
facility: Durham
state: North Carolina
city: New Bern
country: United States
facility: New Bern
state: North Carolina
city: Winston-Salem
country: United States
facility: Winston Salem
state: North Carolina
city: Akron
country: United States
facility: Akron
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Englewood
country: United States
facility: Englewood
state: Ohio
city: Hershey
country: United States
facility: Hershey
state: Pennsylvania
city: Columbia
country: United States
facility: Columbia
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga
state: Tennessee
city: Memphis
country: United States
facility: Memphis
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: 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: 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: 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: Virginia Beach
country: United States
facility: Virginia Beach
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: Cordoba
country: Argentina
facility: Cordoba
city: Sydney
country: Australia
facility: Sydney
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong
state: NS
city: Taringa
country: Australia
facility: Taringa
state: Queensland
city: Adelaide
country: Australia
facility: Adelaide
state: South Australia
city: Nedlands
country: Australia
facility: Nedlands
state: Western Australia
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: 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: Sao Paulo
state: Sao Paulo
city: São Paulo
country: Brazil
facility: São Paulo
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Sao Paulo
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: Sofia
country: Bulgaria
facility: Sofia
state: Sofiya
city: Blagoevgrad
country: Bulgaria
facility: Blagoevgrad
city: Pleven
country: Bulgaria
facility: Pleven
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: 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: Vodňany
country: Czechia
facility: Vodňany
state: Jihocesky
city: Tábor
country: Czechia
facility: Tábor
state: Jihormoravsky Kraj
city: Náchod
country: Czechia
facility: Náchod
state: Kralovehradecky
city: Praha 10
country: Czechia
facility: Praha 10
state: Praha
city: Praha 2
country: Czechia
facility: Praha 2
state: Praha
city: Olomouc
country: Czechia
facility: Olomouc
city: Praha 8 - Libeň
country: Czechia
facility: Praha 8 - Libeň
city: České Budějovice
country: Czechia
facility: České Budějovice
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: Tbilisi
country: Georgia
facility: Tbilisi
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: 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: Remuera
country: New Zealand
facility: Remuera
state: Auckland
city: Palmerston North
country: New Zealand
facility: Palmerston North
state: Manawatu-wanganui
city: Christchurch
country: New Zealand
facility: Christchurch
city: Łódź
country: Poland
facility: Łódź
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: 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: Białystok
country: Poland
facility: Białystok
state: Podlaskie
city: Katowice
country: Poland
facility: Katowice
state: Slaskie
city: Katowice
country: Poland
facility: Katowice
state: Slaskie
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: Porto
country: Portugal
facility: Porto
city: Brasov
country: Romania
facility: Brasov
city: Bucuresti
country: Romania
facility: Bucuresti
city: Bucuresti
country: Romania
facility: Bucuresti
city: Bucuresti
country: Romania
facility: Bucuresti
city: București
country: Romania
facility: București
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: Kyiv
country: Ukraine
facility: Kyiv
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: