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

NCT ID: NCT03204331

Last Updated: 2021-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

623 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-01

Study Completion Date

2021-05-31

Brief Summary

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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

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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.

Conditions

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Endometriosis Related Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Relugolix plus E2/NETA (Group A)

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

Group Type EXPERIMENTAL

Relugolix

Intervention Type DRUG

Relugolix 40-mg tablet administered orally once daily.

Estradiol/norethindrone acetate

Intervention Type DRUG

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

Relugolix plus Delayed E2/NETA (Group B)

Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.

Group Type EXPERIMENTAL

Relugolix

Intervention Type DRUG

Relugolix 40-mg tablet administered orally once daily.

Estradiol/norethindrone acetate

Intervention Type DRUG

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

Estradiol/norethindrone acetate placebo

Intervention Type 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 placebo co-administered with E2/NETA placebo for 24 weeks.

Group Type PLACEBO_COMPARATOR

Estradiol/norethindrone acetate placebo

Intervention Type 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.

Relugolix placebo

Intervention Type DRUG

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

Interventions

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Relugolix

Relugolix 40-mg tablet administered orally once daily.

Intervention Type DRUG

Estradiol/norethindrone acetate

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

Intervention Type DRUG

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.

Intervention Type DRUG

Relugolix placebo

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

Intervention Type DRUG

Other Intervention Names

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TAK-385 MVT-601 E2/NETA

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Myovant Sciences GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Myovant Medical Monitor

Role: STUDY_DIRECTOR

Myovant Sciences

Locations

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Andalusia

Andalusia, Alabama, United States

Site Status

Washington DC

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

Site Status

Aventura

Aventura, Florida, United States

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Deland

DeLand, Florida, United States

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Hialeah

Hialeah, Florida, United States

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Hialeah

Hialeah, Florida, United States

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Margate

Margate, Florida, United States

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Miami

Miami, Florida, United States

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Port St. Lucie

Port Saint Lucie, Florida, United States

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Tampa

Tampa, Florida, United States

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Atlanta

Atlanta, Georgia, United States

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Idaho Falls

Idaho Falls, Idaho, United States

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Park Ridge

Park Ridge, Illinois, United States

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Lafayette

Lafayette, Indiana, United States

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Covington

Covington, Louisiana, United States

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Marrero

Marrero, Louisiana, United States

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Towson

Towson, Maryland, United States

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Saginaw

Saginaw, Michigan, United States

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St. Louis

St Louis, Missouri, United States

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Omaha

Omaha, Nebraska, United States

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Albuquerque

Albuquerque, New Mexico, United States

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New York

New York, New York, United States

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New Bern

New Bern, North Carolina, United States

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Akron

Akron, Ohio, United States

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Columbus

Columbus, Ohio, United States

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Columbus

Columbus, Ohio, United States

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Franklin

Franklin, Ohio, United States

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Columbia

Columbia, South Carolina, United States

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Spartanburg

Spartanburg, South Carolina, United States

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Chattanooga

Chattanooga, Tennessee, United States

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Beaumont

Beaumont, Texas, United States

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Corpus Christi

Corpus Christi, Texas, United States

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Dallas

Dallas, Texas, United States

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Fort Worth

Fort Worth, Texas, United States

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Houston

Houston, Texas, United States

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Irving

Irving, Texas, United States

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San Antonio

San Antonio, Texas, United States

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Sugar Land

Sugar Land, Texas, United States

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Pleasant Grove

Pleasant Grove, Utah, United States

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Salt Lake City

Salt Lake City, Utah, United States

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Virginia Beach

Virginia Beach, Virginia, United States

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Sydney

Sydney, New South Wales, Australia

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Wollongong

Wollongong, New South Wales, Australia

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Sherwood

Sherwood, Queensland, Australia

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Adelaide

Adelaide, South Australia, Australia

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Nedlands

Nedlands, Western Australia, Australia

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Passo Fundo

Passo Fundo, Rio Grande do Sul, Brazil

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Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre

Porto Alegre, São Paulo, Brazil

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São Bernardo do Campo

São Bernardo do Campo, São Paulo, Brazil

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São Paulo

São Paulo, São Paulo, Brazil

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São Paulo

São Paulo, São Paulo, Brazil

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São Paulo

São Paulo, São Paulo, Brazil

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São Paulo

São Paulo, São Paulo, Brazil

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São Paulo

São Paulo, São Paulo, Brazil

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Santiago

Santiago, , Chile

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Santiago

Santiago, , Chile

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Santiago

Santiago, , Chile

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Santiago

Santiago, , Chile

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Tábor

Tábor, Jihormoravsky KRAJ, Czechia

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Písek

Písek, Jihočeský kraj, Czechia

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Praha 2

Prague, Prague, Czechia

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Ceské Budejovice

České Budějovice, , Czechia

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Tbilisi

Tbilisi, Borjomi, Georgia

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Monserrato

Monserrato, Cagliari, Italy

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Catanzaro

Catanzaro, , Italy

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Napoli

Napoli, , Italy

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Pavia

Pavia, , Italy

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Roma

Roma, , Italy

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Birkenhead

Birkenhead, Auckland, New Zealand

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Remuera

Remuera, Auckland, New Zealand

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Tauranga

Tauranga, Bay of Plenty, New Zealand

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Palmerston North

Palmerston North, Manawatu-Wanganui, New Zealand

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Christchurch

Christchurch, , New Zealand

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Poznan

Poznan, Greater Poland Voivodeship, Poland

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Lublin

Lublin, Lublin Voivodeship, Poland

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Lublin

Lublin, Lublin Voivodeship, Poland

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Warszawa

Warsaw, Masovian Voivodeship, Poland

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Warszawa

Warsaw, Masovian Voivodeship, Poland

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Warszawa

Warsaw, Masovian Voivodeship, Poland

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Bialystok

Bialystok, Podlaskie Voivodeship, Poland

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Białystok

Bialystok, Podlaskie Voivodeship, Poland

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Katowice

Katowice, Silesian Voivodeship, Poland

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Lodz

Lodz, Łódź Voivodeship, Poland

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București

Bucharest, București, Romania

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Brasov

Brasov, , Romania

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Bucuresti

Bucharest, , Romania

Site Status

Bucuresti

Bucharest, , Romania

Site Status

Malmö

Malmo, Skåne County, Sweden

Site Status

Countries

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

References

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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.

Reference Type DERIVED
PMID: 37982388 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37283994 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35717987 (View on PubMed)

Other Identifiers

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2017-001632-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MVT-601-3102

Identifier Type: -

Identifier Source: org_study_id

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