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

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).

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.

Eligibility Criteria:
Key Inclusion Criteria:

1. Completed 24 weeks of study drug treatment and study participation in either parent study, MVT-601-3101 or MVT-601-3102.
2. 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.
3. Has agreed to continue to use only study-specified analgesic medications during the study and is not known to be intolerant to these.

Key Exclusion Criteria:

1. Has had a surgical procedure for treatment for endometriosis at any time during the parent study (MVT-601-3101 or MVT-601-3102).
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 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.
4. Has any contraindication to treatment with low-dose E2 and NETA, including:

   1. Known, suspected, or history of breast cancer;
   2. Known or suspected estrogen-dependent neoplasia;
   3. Active deep vein thrombosis or pulmonary embolism, or history of these conditions prior to the Week 24/Baseline visit;
   4. History of or active arterial thromboembolic disease, including stroke and myocardial infarction;
   5. Known anaphylactic reaction or angioedema or hypersensitivity to E2 or NETA;
   6. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilia disorders, including Factor V Leiden;
   7. Migraine with aura;
   8. History of porphyria.
5. 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):

   1. Alanine aminotransferase or aspartate aminotransferase \> 2.0 times the upper limit of normal (ULN); or
   2. Bilirubin (total bilirubin) \> 1.5 x ULN (or \> 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome).