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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03204331




Registration number
NCT03204331
Ethics application status
Date submitted
27/06/2017
Date registered
2/07/2017
Date last updated
29/06/2020

Titles & IDs
Public title
SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
Scientific 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
Secondary ID [1] 0 0
2017-001632-19
Secondary ID [2] 0 0
MVT-601-3102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis Related Pain 0 0
Condition category
Condition code
Reproductive Health and Childbirth 0 0 0 0
Other reproductive health and childbirth disorders
Reproductive Health and Childbirth 0 0 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Relugolix
Treatment: Drugs - Estradiol/norethindrone acetate
Treatment: Drugs - Estradiol/norethindrone acetate placebo
Treatment: Drugs - Relugolix placebo

Experimental: Relugolix plus E2/NETA (Group A) - Relugolix co-administered with E2/NETA for 24 weeks.

Experimental: 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.

Placebo Comparator: Placebo (Group C) - Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.


Treatment: Drugs: Relugolix
Relugolix 40-mg tablet administered orally once daily.

Treatment: Drugs: Estradiol/norethindrone acetate
Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.

Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 24 or EOT
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Week 24 or EOT
Secondary outcome [1] 0 0
Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24 - Assessed using the Pain Domain of the EHP-30 questionnaire.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [2] 0 0
Baseline, Week 24 or EOT
Secondary outcome [3] 0 0
Change From Baseline In NMPP NRS Score At Week 24 Or EOT - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [3] 0 0
Baseline, Week 24 or EOT
Secondary outcome [4] 0 0
Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [4] 0 0
Baseline, Week 24 or EOT
Secondary outcome [5] 0 0
Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT - Assessed using an NRS score (11-point scale) for dyspareunia recorded daily in an e-Diary.
Timepoint [5] 0 0
Baseline, Week 24 or EOT
Secondary outcome [6] 0 0
Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT - Assessed based on usage of protocol-specified opioids for endometriosis-associated pain recorded daily in an e-Diary.
Timepoint [6] 0 0
Week 24 or EOT
Secondary outcome [7] 0 0
Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT - Assessed based on usage of protocol-specified analgesic for endometriosis-associated pain recorded daily in an e-Diary.
Timepoint [7] 0 0
Baseline, Week 24 or EOT
Secondary outcome [8] 0 0
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 - Assessed using the pain domain of the EHP-30 questionnaire.
Timepoint [8] 0 0
Baseline to Week 24
Secondary outcome [9] 0 0
Dysmenorrhea Responder Rate By Month - The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
NMPP Responder Rate By Month - The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Timepoint [10] 0 0
Baseline to Week 24
Secondary outcome [11] 0 0
Change In Dysmenorrhea NRS Score By Month - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [11] 0 0
Baseline to Week 24
Secondary outcome [12] 0 0
Change In NMPP NRS Score By Month - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [12] 0 0
Baseline to Week 24
Secondary outcome [13] 0 0
Change In Overall Pelvic Pain NRS Score By Month - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [13] 0 0
Baseline to Week 24
Secondary outcome [14] 0 0
Change In Dyspareunia NRS Score By Month - Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Timepoint [14] 0 0
Baseline to Week 24
Secondary outcome [15] 0 0
Change From Baseline In Ibuprofen Use At Week 24 Or EOT - Assessed using ibuprofen pill counts for endometriosis-associated pain recorded daily in an e-Diary.
Timepoint [15] 0 0
Baseline, Week 24
Secondary outcome [16] 0 0
Change From Baseline In Opioid Use At Week 24 Or EOT - Assessed using opioid pill counts for endometriosis-associated pain recorded daily in an e-Diary.
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT - Assessed using the subject modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an e-Diary.
Timepoint [17] 0 0
Baseline, Week 24 or EOT
Secondary outcome [18] 0 0
Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT - Assessed using the subject modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an e-Diary.
Timepoint [18] 0 0
Baseline, Week 24 or EOT
Secondary outcome [19] 0 0
Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT - Assessed using the subject modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an e-Diary.
Timepoint [19] 0 0
Baseline, Week 24 or EOT
Secondary outcome [20] 0 0
Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At 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.
Timepoint [20] 0 0
Baseline, Week 24
Secondary outcome [21] 0 0
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At 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.
Timepoint [21] 0 0
Week 24
Secondary outcome [22] 0 0
Change From Baseline In PGA For NMPP Symptom Severity At Week 24 - The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.
Timepoint [22] 0 0
Baseline, Week 24
Secondary outcome [23] 0 0
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24 - The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.
Timepoint [23] 0 0
Week 24
Secondary outcome [24] 0 0
Change From Baseline In PGA For Pain Severity At Week 24 - The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Timepoint [24] 0 0
Baseline, Week 24
Secondary outcome [25] 0 0
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24 - The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Timepoint [25] 0 0
Week 24
Secondary outcome [26] 0 0
Change From Baseline In PGA For Function At Week 24 - The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Timepoint [26] 0 0
Baseline, Week 24
Secondary outcome [27] 0 0
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24 - The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Timepoint [27] 0 0
Week 24
Secondary outcome [28] 0 0
Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At 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.
Timepoint [28] 0 0
Week 24
Secondary outcome [29] 0 0
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24 - The PGIC for NMPP is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.
Timepoint [29] 0 0
Week 24
Secondary outcome [30] 0 0
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24 - The PGIC for dyspareunia is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during sexual intercourse.
Timepoint [30] 0 0
Week 24
Secondary outcome [31] 0 0
Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24 - Assessed using the non-pain domains (Control and Powerlessness, Social Support, Emotional Well-Being, and Self-Image) of the EHP-30 questionnaire.
Timepoint [31] 0 0
Baseline, Week 24
Secondary outcome [32] 0 0
Change From Baseline In The EHP-30 Scale Total Score At Week 24 - Assessed using the total score of the EHP-30 questionnaire.
Timepoint [32] 0 0
Baseline, Week 24
Secondary outcome [33] 0 0
Change From Baseline In The EHP Work Domain Score At Week 24 - The EHP Work domain is a 5-item questionnaire that assesses impact of pain on ability to work.
Timepoint [33] 0 0
Baseline, Week 24
Secondary outcome [34] 0 0
Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24 - The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.
Timepoint [34] 0 0
Baseline, Week 24
Secondary outcome [35] 0 0
Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24 - The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.
Timepoint [35] 0 0
Baseline, Week 24
Secondary outcome [36] 0 0
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA - 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.
Timepoint [36] 0 0
Week 24 or EOT
Secondary outcome [37] 0 0
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA - 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.
Timepoint [37] 0 0
Week 24 or EOT
Secondary outcome [38] 0 0
Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA - Assessed using the Pain Domain of the EHP-30 questionnaire.
Timepoint [38] 0 0
Baseline, Week 24
Secondary outcome [39] 0 0
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA - Assessed using the pain domain of the EHP-30 questionnaire.
Timepoint [39] 0 0
Baseline to Week 24
Secondary outcome [40] 0 0
Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12 - Assessed by dual-energy X-ray absorptiometry (DXA) scan.
Timepoint [40] 0 0
Baseline, Week 12
Secondary outcome [41] 0 0
Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24 - Assessed by DXA scan.
Timepoint [41] 0 0
Baseline, Week 24
Secondary outcome [42] 0 0
Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B
Timepoint [42] 0 0
Week 12
Secondary outcome [43] 0 0
Change From Baseline In Serum Concentrations Of Luteinizing Hormone, Follicle Stimulating Hormone, Estradiol, And Progesterone - Blood samples will be collected from participants for hormonal measurements.
Timepoint [43] 0 0
Baseline, Week 24

Eligibility
Key inclusion criteria
Key

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.

Key
Minimum age
18 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
No
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Sydney - Sydney
Recruitment hospital [2] 0 0
Wollongong - Wollongong
Recruitment hospital [3] 0 0
Sherwood - Sherwood
Recruitment hospital [4] 0 0
Adelaide - Adelaide
Recruitment hospital [5] 0 0
Nedlands - Nedlands
Recruitment postcode(s) [1] 0 0
2000 - Sydney
Recruitment postcode(s) [2] 0 0
2522 - Wollongong
Recruitment postcode(s) [3] 0 0
4068 - Sherwood
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
New Mexico
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
Brazil
State/province [22] 0 0
RIO Grande DO SUL
Country [23] 0 0
Brazil
State/province [23] 0 0
Rio Grande Do Sul
Country [24] 0 0
Brazil
State/province [24] 0 0
SAO Paulo
Country [25] 0 0
Chile
State/province [25] 0 0
Santiago
Country [26] 0 0
Czechia
State/province [26] 0 0
Jihocesky KRAJ
Country [27] 0 0
Czechia
State/province [27] 0 0
Jihormoravsky KRAJ
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha
Country [29] 0 0
Czechia
State/province [29] 0 0
Ceské Budejovice
Country [30] 0 0
Georgia
State/province [30] 0 0
Borjomi
Country [31] 0 0
Italy
State/province [31] 0 0
Cagliari
Country [32] 0 0
Italy
State/province [32] 0 0
Catanzaro
Country [33] 0 0
Italy
State/province [33] 0 0
Napoli
Country [34] 0 0
Italy
State/province [34] 0 0
Pavia
Country [35] 0 0
Italy
State/province [35] 0 0
Roma
Country [36] 0 0
New Zealand
State/province [36] 0 0
Auckland
Country [37] 0 0
New Zealand
State/province [37] 0 0
Bay Of Plenty
Country [38] 0 0
New Zealand
State/province [38] 0 0
Manawatu-wanganui
Country [39] 0 0
New Zealand
State/province [39] 0 0
Christchurch
Country [40] 0 0
Poland
State/province [40] 0 0
Lodzkie
Country [41] 0 0
Poland
State/province [41] 0 0
Lubelskie
Country [42] 0 0
Poland
State/province [42] 0 0
Mazowieckie
Country [43] 0 0
Poland
State/province [43] 0 0
Podlaskie
Country [44] 0 0
Poland
State/province [44] 0 0
Slaskie
Country [45] 0 0
Poland
State/province [45] 0 0
Wielkopolskie
Country [46] 0 0
Romania
State/province [46] 0 0
Bucuresti
Country [47] 0 0
Romania
State/province [47] 0 0
Brasov
Country [48] 0 0
Sweden
State/province [48] 0 0
Skane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Myovant Sciences GmbH
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03204331
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Myovant Medical Monitor
Address 0 0
Myovant Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications