SPIRIT EXTENSION: An International Phase 3 Open-Label, Single-Arm, Safety and Efficacy Extension Study to Evaluate Relugolix Co-Administered With Low-Dose Estradiol and Norethindrone Acetate in Women With Endometriosis-Associated Pain
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 802
- 试验地点
- 136
- 主要终点
- Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 52
研究概览
简要总结
The purpose of this study is to evaluate the long-term efficacy and safety of relugolix 40 milligram (mg) once daily co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) for up to 104 weeks on endometriosis-associated pain in participants who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3101 or MVT-601-3102).
详细描述
This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that will enroll eligible participants who have completed their participation in one of the phase 3 randomized, double-blind, placebo-controlled parent studies, MVT-601-3101 (SPIRIT 1 - NCT03204318) or MVT-601-3102 (SPIRIT 2 - NCT03204331). All participants will receive relugolix 40 mg orally once daily co-administered with low-dose E2 (1.0 mg) and NETA (0.5 mg) for 80 weeks.
Approximately 800 women with endometriosis-associated pain will be enrolled, after having completed a 24-week treatment period in one of the parent studies. The objectives of the study are to evaluate long-term efficacy and safety through up to 104 weeks of treatment (including treatment during the parent study) of relugolix co-administered with low-dose E2/NETA.
Baseline procedures for this extension study will be performed on the same day as the Week 24 Visit of the parent study. This visit, referred to as the "Week 24/Baseline Visit, will be defined as the date of completion of the last Week 24 procedure in the parent study. Participants will have received their last dose of study drug in the parent study on the day prior to the Week 24/Baseline Visit and will receive their first dose of study drug for this extension study in the clinic after the participant is determined to be eligible for this extension study and has provided informed consent to participate. The administration of the first dose of study drug for MVT-601-3103 will define enrollment into this study. Study participants will then take the open-label study treatment orally, once daily for 80 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 51 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Completed 24 weeks of study drug treatment and study participation in either parent study, MVT-601-3101 or MVT-601-
- •Is not expected to undergo gynecological surgery or other surgical procedures for treatment of endometriosis (including ablation, shaving, or excision) during the study, including during the Follow-Up Period, and the participant does not desire such treatment during this time frame.
- •Has agreed to continue to use only study-specified analgesic medications during the study and is not known to be intolerant to these.
排除标准
- •Has had a surgical procedure for treatment for endometriosis at any time during the parent study (MVT-601-3101 or MVT-601-3102).
- •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.
- •Has a Z-score < -2.0 or has a ≥ 7% decrease in bone mineral density from the parent study Baseline at lumbar spine, total hip, or femoral neck based on the parent study Week 24 DXA assessment of bone mineral density.
- •Has any contraindication to treatment with low-dose E2 and NETA, including:
- •Known, suspected, or history of breast cancer;
- •Known or suspected estrogen-dependent neoplasia;
- •Active deep vein thrombosis or pulmonary embolism, or history of these conditions prior to the Week 24/Baseline visit;
- •History of or active arterial thromboembolic disease, including stroke and myocardial infarction;
- •Known anaphylactic reaction or angioedema or hypersensitivity to E2 or NETA;
- •Known protein C, protein S, or antithrombin deficiency, or other known thrombophilia disorders, including Factor V Leiden;
- •Migraine with aura;
- •History of porphyria.
- •Had any of the following clinical laboratory abnormalities at the parent study Week 20 visit or, if available, any subsequent visit in one of the parent studies (MVT-601-3101 or MVT-601-3102):
- •Alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of normal (ULN); or
- •Bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome).
研究组 & 干预措施
Relugolix plus E2/NETA
Relugolix co-administered with E2/NETA for 80 weeks.
干预措施: Relugolix (Drug)
Relugolix plus E2/NETA
Relugolix co-administered with E2/NETA for 80 weeks.
干预措施: Estradiol/norethindrone acetate (Drug)
结局指标
主要结局
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 52
时间窗: Week 52
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 52 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 104
时间窗: Week 104
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 104 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 104
时间窗: Week 104
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 104 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 52
时间窗: Week 52
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 52 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
次要结局
- Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 52(Week 52)
- Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 52(Week 52)
- Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 104(Week 104)
- Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 52(Week 52)
- Percentage Of Participants Not Using Opioids For Endometriosis-associated Pain At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 52(Week 52)
- Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 52(Week 52)
- Percentage Of Participants Not Using Analgesics For Endometriosis-associated Pain At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 104(Week 104)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104(Week 104)
- Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 52(Week 52)
- Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52(Week 52)
- Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104(Week 104)
- Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 52(Week 52)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52(Week 52)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104(Week 104)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 104(Week 104)
- Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 104(Week 104)
- Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52(Week 52)
- Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 52(Week 52)
- Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 52(Week 52)
- Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 104(Week 104)