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

NCT03204331 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: MVT-601-31022017-001632-19
• Study Type: interventional
• Target: 623
• Locations: 11 countries
• Sites: 91

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.

Conditions

Endometriosis Related Pain

Keywords

Endometriosis; Pain; Dysmenorrhea

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (43)

• Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24

  Baseline, Week 24

• Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT

  Baseline, Week 24 or EOT

• Change From Baseline In NMPP NRS Score At Week 24 Or EOT

  Baseline, Week 24 or EOT

• Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT

  Baseline, Week 24 or EOT

• Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT

  Baseline, Week 24 or EOT

Study Arms (3)

Relugolix plus E2/NETA (Group A)

EXPERIMENTAL

Relugolix co-administered with E2/NETA for 24 weeks.

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.

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.

Drug: Estradiol/norethindrone acetate placebo; Drug: Relugolix placebo

Interventions

Relugolix DRUG

Relugolix 40-mg tablet administered orally once daily.

Also known as: TAK-385, MVT-601

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate DRUG

Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.

Also known as: E2/NETA

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate placebo DRUG

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.

Placebo (Group C); Relugolix plus Delayed E2/NETA (Group B)

Relugolix placebo DRUG

Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Placebo (Group C)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Myovant Sciences GmbH: lead

Study Sites (91)

Andalusia

Andalusia, Alabama, 36420, United States

Location

Washington DC

Washington D.C., District of Columbia, 20036, United States

Location

Aventura

Aventura, Florida, 33180, United States

Location

Deland

DeLand, Florida, 32720, United States

Location

Hialeah

Hialeah, Florida, 33012, United States

Location

Hialeah

Hialeah, Florida, 33016, United States

Location

Margate

Margate, Florida, 33063, United States

Location

Miami

Miami, Florida, 33176, United States

Location

Port St. Lucie

Port Saint Lucie, Florida, 34952, United States

Location

Tampa

Tampa, Florida, 33606, United States

Location

Atlanta

Atlanta, Georgia, 30312, United States

Location

Idaho Falls

Idaho Falls, Idaho, 83404, United States

Location

Park Ridge

Park Ridge, Illinois, 60068, United States

Location

Lafayette

Lafayette, Indiana, 47905, United States

Location

Covington

Covington, Louisiana, 70433, United States

Location

Marrero

Marrero, Louisiana, 70072, United States

Location

Towson

Towson, Maryland, 21204, United States

Location

Saginaw

Saginaw, Michigan, 48602, United States

Location

St. Louis

St Louis, Missouri, 63141, United States

Location

Omaha

Omaha, Nebraska, 68124, United States

Location

Albuquerque

Albuquerque, New Mexico, 87102, United States

Location

New York

New York, New York, 10038, United States

Location

New Bern

New Bern, North Carolina, 28562, United States

Location

Akron

Akron, Ohio, 44313, United States

Location

Columbus

Columbus, Ohio, 43231, United States

Location

Columbus

Columbus, Ohio, 43235, United States

Location

Franklin

Franklin, Ohio, 45005, United States

Location

Columbia

Columbia, South Carolina, 29201, United States

Location

Spartanburg

Spartanburg, South Carolina, 29301, United States

Location

Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Beaumont

Beaumont, Texas, 77702, United States

Location

Corpus Christi

Corpus Christi, Texas, 78412, United States

Location

Dallas

Dallas, Texas, 75231, United States

Location

Fort Worth

Fort Worth, Texas, 76104, United States

Location

Houston

Houston, Texas, 77054, United States

Location

Irving

Irving, Texas, 75062, United States

Location

San Antonio

San Antonio, Texas, 78258, United States

Location

Sugar Land

Sugar Land, Texas, 77479, United States

Location

Pleasant Grove

Pleasant Grove, Utah, 84062, United States

Location

Salt Lake City

Salt Lake City, Utah, 84102, United States

Location

Virginia Beach

Virginia Beach, Virginia, 23502, United States

Location

Sydney

Sydney, New South Wales, 2000, Australia

Location

Wollongong

Wollongong, New South Wales, 2522, Australia

Location

Sherwood

Sherwood, Queensland, 4075, Australia

Location

Adelaide

Adelaide, South Australia, 5000, Australia

Location

Nedlands

Nedlands, Western Australia, 6009, Australia

Location

Passo Fundo

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

Porto Alegre

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

Porto Alegre

Porto Alegre, Rio Grande do Sul, 90510-040, Brazil

Location

Porto Alegre

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Porto Alegre

Porto Alegre, São Paulo, 90035-903, Brazil

Location

São Bernardo do Campo

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

São Paulo

São Paulo, São Paulo, 01317-000, Brazil

Location

São Paulo

São Paulo, São Paulo, 01323-900, Brazil

Location

São Paulo

São Paulo, São Paulo, 04023-062, Brazil

Location

São Paulo

São Paulo, São Paulo, 04266-010, Brazil

Location

São Paulo

São Paulo, São Paulo, 04708-001, Brazil

Location

Santiago

Santiago, 7510186, Chile

Location

Santiago

Santiago, 8320165, Chile

Location

Santiago

Santiago, 8360160, Chile

Location

Santiago

Santiago, 8880465, Chile

Location

Tábor

Tábor, Jihormoravsky KRAJ, 390 03, Czechia

Location

Písek

Písek, Jihočeský kraj, 39701, Czechia

Location

Praha 2

Prague, Prague, 128 08, Czechia

Location

Ceské Budejovice

České Budějovice, 370 01, Czechia

Location

Tbilisi

Tbilisi, Borjomi, 0159, Georgia

Location

Monserrato

Monserrato, Cagliari, 09042, Italy

Location

Catanzaro

Catanzaro, 88100, Italy

Location

Napoli

Napoli, 80131, Italy

Location

Pavia

Pavia, 27100, Italy

Location

Roma

Roma, 00168, Italy

Location

Birkenhead

Birkenhead, Auckland, 0626, New Zealand

Location

Remuera

Remuera, Auckland, 1050, New Zealand

Location

Tauranga

Tauranga, Bay of Plenty, 3112, New Zealand

Location

Palmerston North

Palmerston North, Manawatu-Wanganui, 4442, New Zealand

Location

Christchurch

Christchurch, 8013, New Zealand

Location

Poznan

Poznan, Greater Poland Voivodeship, 60-185, Poland

Location

Lublin

Lublin, Lublin Voivodeship, 20-064, Poland

Location

Lublin

Lublin, Lublin Voivodeship, 20-093, Poland

Location

Warszawa

Warsaw, Masovian Voivodeship, 02-066, Poland

Location

Warszawa

Warsaw, Masovian Voivodeship, 02-201, Poland

Location

Warszawa

Warsaw, Masovian Voivodeship, 02-929, Poland

Location

Bialystok

Bialystok, Podlaskie Voivodeship, 15-224, Poland

Location

Białystok

Bialystok, Podlaskie Voivodeship, 15-464, Poland

Location

Katowice

Katowice, Silesian Voivodeship, 40-301, Poland

Location

Lodz

Lodz, Łódź Voivodeship, 90-602, Poland

Location

București

Bucharest, București, 20475, Romania

Location

Brasov

Brasov, 500091, Romania

Location

Bucuresti

Bucharest, 012071, Romania

Location

Bucuresti

Bucharest, 022441, Romania

Location

Malmö

Malmo, Skåne County, 20502, Sweden

Location

Related Publications (3)

• 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.

  PMID: 37982388 DERIVED

• Hunsche 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.

  PMID: 37283994 DERIVED

• 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.

  PMID: 35717987 DERIVED

MeSH Terms

Conditions

Endometriosis; Pain; Dysmenorrhea

Interventions

relugolix; estradiol, norethindrone drug combination; Estradiol

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances; Pathologic Processes; Pelvic Pain

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Myovant Medical Monitor

  Myovant Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: July 2, 2017
• Study Start: November 1, 2017
• Primary Completion: April 1, 2020
• Study Completion: May 31, 2021
• Last Updated: June 28, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); US (41); PL (10); BR (11); AU (5); RO (4); CL (4); CZ (4); GE (1); IT (5); NZ (5)