SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

• ClinicalTrials.gov Identifier: NCT03204318
• Recruitment Status: Recruiting
• First Posted: July 2, 2017
• Last Update Posted: October 10, 2019
• Sponsor: Myovant Sciences GmbH
• Information provided by (Responsible Party): Myovant Sciences GmbH

Study Description

Brief Summary:

The purpose of this study is to determine the benefit and safety of relugolix 40 mg once daily, co-administered with low-dose estradiol and norethindrone acetate compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.

Condition or disease	Intervention/treatment	Phase
Endometriosis Related Pain	Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Placebo for E2/NETA; Drug: Placebo for relugolix	Phase 3

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 estradiol (1.0 mg) and norethindrone acetate (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).

Once eligibility has been confirmed, patients will be randomized on Baseline Day 1 to Treatment Group A, B or C, and will begin double-blinded study drug treatment on Day 1. Between the Baseline Day 1 and Week 24 visits, patients will attend visits every 4 weeks, and will take the blinded study treatment (1 tablet and 1 capsule) orally once daily for 24 weeks. The last dose of study drug will be taken on the day prior to the Week 24 visit.

Eligible patients, including women randomized to placebo, will be offered the opportunity to enroll in a 28-week open label extension study where patients will receive relugolix co-administered with low-dose estradiol and norethindrone acetate. Patients who do not enroll into the extension study will have a Follow-Up visit approximately 30 days after the patient's last dose of study drug.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 7, 2017
• Estimated Primary Completion Date: December 15, 2019
• Estimated Study Completion Date: June 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Relugolix plus E2/NETA (Group A); Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for 24 weeks.	Drug: Relugolix; Relugolix 40 mg tablet administered orally once daily; Other Name: TAK-385; Drug: Estradiol/norethindrone acetate; Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily; Other Name: E2/NETA, low-dose hormonal add-back
Experimental: Relugolix -> relugolix plus E2/NETA (Group B); Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks, followed by relugolix 40 mg co-administered with estradiol/norethindrone acetate (1.0/0.5 mg) for 12 weeks.	Drug: Relugolix; Relugolix 40 mg tablet administered orally once daily; Other Name: TAK-385; Drug: Estradiol/norethindrone acetate; Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily; Other Name: E2/NETA, low-dose hormonal add-back; Drug: Placebo for E2/NETA; Placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor
Placebo Comparator: Placebo (Group C); Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.	Drug: Placebo for E2/NETA; Placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor; Drug: Placebo for relugolix; Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color and odor

Outcome Measures

Primary Outcome Measures :

1. Proportion of responders based on daily assessment of dysmenorrhea [ Time Frame: 24 weeks ]
   Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary.
2. Proportion of responders based on daily assessment of nonmenstrual pelvic pain [ Time Frame: 24 weeks ]
   Assessed using a NRS score (11-point scale) for pain recorded daily in an electronic diary.

Secondary Outcome Measures :

1. Change in function due to endometriosis associated pain [ Time Frame: from Baseline up to Week 24 ]
   Assessed using the Pain Domain of the Endometriosis Health Profile (EHP-30) questionnaire.
2. Change in dysmenorrhea NRS scores [ Time Frame: from Baseline up to Week 24 ]
   Assessed using a NRS score (11-point scale) for pain recorded daily in an electronic diary.
3. Change in nonmenstrual pelvic pain NRS scores [ Time Frame: from Baseline up to Week 24 ]
   Assessed using a NRS score (11-point scale) for pain recorded daily in an electronic diary.
4. Change in dyspareunia NRS scores [ Time Frame: from Baseline up to Week 24 ]
   Assessed using a NRS score (11-point scale) for pain recorded daily in an electronic diary.
5. Patient Global Assessment (PGA) for dysmenorrhea [ Time Frame: from Baseline up to Week 24 ]
   The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants impression of the severity of pain during their menstrual cycle.
6. Patient Global Impression of Change (PGIC) for dysmenorrhea [ Time Frame: from Baseline up to Week 24 ]
   The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participants impression of change in the severity of pain during their menstrual cycle.
7. Patient Global Assessment (PGA) for nonmenstrual pelvic pain [ Time Frame: from Baseline up to Week 24 ]
   The PGA for nonmenstrual pelvic pain is a 1-item questionnaire designed to assess participants impression of the severity of pain when they are not menstruating.
8. Patient Global Impression of Change (PGIC) for nonmenstrual pelvic pain [ Time Frame: from Baseline up to Week 24 ]
   The PGIC for nonmenstrual pelvic pain is a 1-item questionnaire designed to assess participants impression of change in the severity of pain when they are not menstruating.
9. Patient Global Impression of Change (PGIC) for dyspareunia [ Time Frame: from Baseline up to Week 24 ]
   The PGIC for dyspareunia is a 1-item questionnaire designed to assess participants impression of change in the severity of their pain during sexual intercourse.
10. Change in the mean dysmenorrhea functional impairment [ Time Frame: from Baseline up to Week 24 ]
    Assessed using the subject modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an electronic diary.
11. Change in the mean nonmenstrual pelvic pain functional impairment [ Time Frame: from Baseline up to Week 24 ]
    Assessed using the subject modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an electronic diary.
12. Change in the mean dyspareunia functional impairment [ Time Frame: from Baseline up to Week 24 ]
    Assessed using the subject modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an electronic diary.
13. Change in Patient Global Assessment (PGA) for function [ Time Frame: from Baseline up to Week 24 ]
    The PGA for function is a 1-item questionnaire designed to assess participants impression of how their pain affected their usual activities.
14. Bone Mineral Density (BMD) [ Time Frame: from Baseline up to Week 24 ]
    Assessed by dual-energy X-ray absorptiometry (DXA) scan.
15. The number and percentage of participants with adverse events (AE) as a measure of safety and tolerability [ Time Frame: up to 24 weeks ]
    Assessed by frequency and severity of AEs and serious AEs.
16. Pharmacokinetics of relugolix [ Time Frame: up to 24 weeks ]
    Blood samples will be collected from participants for measurement of relugolix concentrations.
17. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) estradiol (E2) and progesterone (P) [ Time Frame: up to 24 weeks ]
    Blood samples will be collected from participants for hormonal measurements.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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 with surgical visualization of endometriosis via laparoscopy or laparotomy performed within 10 years prior to signing the informed consent form.

4. During the Run-In 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.

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 gynecological surgery or other 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 identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.

Contacts and Locations

Contacts

Contact: Clinical Trials at Myovant; 650-278-8743; ClinicalTrials@Myovant.com

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Sponsors and Collaborators

Myovant Sciences GmbH

Investigators

• Study Director: Myovant Medical Monitor; Myovant Sciences

More Information

• Responsible Party: Myovant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT03204318 History of Changes
• Other Study ID Numbers: MVT-601-3101; 2017-001588-19 ( EudraCT Number )
• First Posted: July 2, 2017
• Last Update Posted: October 10, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Myovant Sciences GmbH:

Endometriosis; Pain; Dysmenorrhea

Additional relevant MeSH terms:

Endometriosis; Genital Diseases, Female; Estradiol 3-benzoate; Estradiol 17 beta-cypionate; Norethindrone; Norethindrone Acetate; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral