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

Myovant Sciences

Status and phase: Completed; Phase 3

Conditions: Endometriosis Related Pain

Treatments: Drug: Relugolix placebo; Drug: Estradiol/norethindrone acetate placebo; Drug: Estradiol/norethindrone acetate; Drug: Relugolix

Study type: Interventional

Funder types: Industry

Identifiers

NCT03204331

2017-001632-19 (EudraCT Number)

MVT-601-3102

Details and patient eligibility

About

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.

Full 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 E2 (1.0 mg) and NETA (0.5 mg), compared with placebo.

Approximately 600 women with endometriosis-associated pain were 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).

Eligible participants were randomized on Baseline Day 1 to Treatment Group A, B, or C, in the double-blind period.

Eligible participants, including those randomized to placebo, were offered the opportunity to enroll in an 80-week open label extension study where participants received relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a Follow-Up visit approximately 30 days after the participant's last dose of study drug.

Enrollment: 623 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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623 participants in 3 patient groups, including a placebo group

Relugolix plus E2/NETA (Group A)

Experimental group

Description:

Relugolix co-administered with E2/NETA for 24 weeks.

Treatment:

Drug: Estradiol/norethindrone acetate

Drug: Relugolix

Relugolix plus Delayed E2/NETA (Group B)

Experimental group

Description:

Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.

Treatment:

Drug: Estradiol/norethindrone acetate

Drug: Relugolix

Drug: Estradiol/norethindrone acetate placebo

Placebo (Group C)

Placebo Comparator group

Description:

Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.

Treatment:

Drug: Estradiol/norethindrone acetate placebo

Drug: Relugolix placebo