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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

Tracking Information
First Submitted Date  ICMJE June 27, 2017
First Posted Date  ICMJE July 2, 2017
Last Update Posted Date October 14, 2019
Actual Study Start Date  ICMJE November 1, 2017
Estimated Primary Completion Date December 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 28, 2017)
  • Proportion of responders based on daily assessment of dysmenorrhea [ Time Frame: 24 weeks ]
    As recorded in a daily electronic diary
  • Proportion of responders based on daily assessment of nonmenstrual pelvic pain [ Time Frame: 24 weeks ]
    As recorded in a daily electronic diary
Change History Complete list of historical versions of study NCT03204331 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Bone Mineral Density (BMD) [ Time Frame: from Baseline up to Week 24 ]
    Assessed by dual-energy X-ray absorptiometry (DXA) scan.
  • 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.
  • Pharmacokinetics of relugolix [ Time Frame: up to 24 weeks ]
    Blood samples will be collected from participants for measurement of relugolix concentrations.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2017)
Change from Baseline in the Endometriosis Health Profile (EHP)-30 Pain Domain Group [ Time Frame: 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Endometriosis Related Pain
Intervention  ICMJE
  • 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
  • Drug: Placebo for relugolix
    Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color and odor
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Relugolix
    • Drug: Estradiol/norethindrone acetate
  • 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.
    Interventions:
    • Drug: Relugolix
    • Drug: Estradiol/norethindrone acetate
    • Drug: Placebo for E2/NETA
  • Placebo Comparator: Placebo (Group C)
    Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
    Interventions:
    • Drug: Placebo for E2/NETA
    • Drug: Placebo for relugolix
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 28, 2017)
600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2020
Estimated Primary Completion Date December 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   Chile,   Czechia,   Georgia,   Italy,   New Zealand,   Poland,   Romania,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03204331
Other Study ID Numbers  ICMJE MVT-601-3102
2017-001632-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Myovant Sciences GmbH
Study Sponsor  ICMJE Myovant Sciences GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Myovant Medical Monitor Myovant Sciences
PRS Account Myovant Sciences GmbH
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP