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

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ClinicalTrials.gov Identifier: NCT03204331
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Myovant Sciences GmbH

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : December 15, 2019
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Relugolix plus E2/NETA (Group A)
Relugolix 40 mg tablet 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




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 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Bone Mineral Density (BMD) [ Time Frame: from Baseline up to Week 24 ]
    Assessed by dual-energy X-ray absorptiometry (DXA) scan.

  14. 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.

  15. Pharmacokinetics of relugolix [ Time Frame: up to 24 weeks ]
    Blood samples will be collected from participants for measurement of relugolix concentrations.

  16. 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.



Information from the National Library of Medicine

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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

    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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03204331


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United States, Alabama
Andalusia
Andalusia, Alabama, United States, 34420
United States, Colorado
Lakewood
Lakewood, Colorado, United States, 80228
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Łódź, Lodzkie, Poland, 90-602
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Stockholm, Sweden, 171 76
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Bristol
Bristol, England, United Kingdom, BS2 8EG
Sponsors and Collaborators
Myovant Sciences GmbH
Investigators
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Study Director: Myovant Medical Monitor Myovant Sciences

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Responsible Party: Myovant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03204331     History of Changes
Other Study ID Numbers: MVT-601-3102
2017-001632-19 ( EudraCT Number )
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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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