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

Sponsor

Myovant Sciences GmbH (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03654274

Collaborator

(none)

803

Enrollment

169

Locations

Arm

54.5

Anticipated Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Relugolix Drug: Estradiol/norethindrone acetate	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

803 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open label extensionOpen label extension

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 22, 2018

Actual Primary Completion Date :

Dec 16, 2021

Anticipated Study Completion Date :

Dec 6, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relugolix plus E2/NETA Relugolix co-administered with E2/NETA for 80 weeks.	Drug: Relugolix Relugolix 40-mg tablet administered orally once daily Other Names: TAK-385 MVT-601 Drug: Estradiol/norethindrone acetate Capsule containing co-formulated tablet of E2 (1.0 mg) and NETA (0.5 mg) administered orally once daily Other Names: E2/NETA low-dose hormonal add-back

Arm

Intervention/Treatment

Experimental: Relugolix plus E2/NETA

Relugolix co-administered with E2/NETA for 80 weeks.

Drug: Relugolix

Relugolix 40-mg tablet administered orally once daily

Other Names:

TAK-385

MVT-601

Drug: Estradiol/norethindrone acetate

Capsule containing co-formulated tablet of E2 (1.0 mg) and NETA (0.5 mg) administered orally once daily

Other Names:

E2/NETA

low-dose hormonal add-back

Outcome Measures

Primary Outcome Measures

Proportion Of Women Who Respond Or Maintain Response Based On Assessment Of Dysmenorrhea At Week 52 And Week 104 [Week 52 and Week 104]
Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary).
Proportion Of Women Who Respond Or Maintain Response Based On Assessment Of Non-Menstrual Pelvic Pain (NMPP) At Week 52 And Week 104 [Week 52 and Week 104]
Assessed using a NRS score (11-point scale) for pain recorded daily in an e-Diary.

Secondary Outcome Measures

Change From The Parent Study Baseline In Function Due To Endometriosis-associated Pain At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using the Pain Domain of the Endometriosis Health Profile (EHP)-30 questionnaire.
Change From Parent Study Baseline In Dysmenorrhea NRS Scores At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using a NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change From Parent Study Baseline In Mean NMPP NRS Scores At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using a NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change From Parent Study Baseline In Dyspareunia NRS Scores At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using a NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change From Parent Study Baseline In Overall NRS Scores At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using a NRS score (11-point scale) for overall pain recorded daily in an e-Diary.
Proportion Of Participants Not Using Opioids At Week 52 And Week 104 [Week 52 and Week 104]
Assessed using study-specified opioids recorded daily in e-Diary.
Proportion Of Participants Not Using Rescue Analgesics At Week 52 And Week 104 [Week 52 and Week 104]
Assessed using study-specified opioids recorded daily in e-Diary.
Proportion Of Participants Who Are Better Or Much Better On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 52 [Week 52]
The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participant's impression of change in the severity of pain during their menstrual cycle.
Proportion Of Participants Who Are Better Or Much Better On The PGIC For NMPP At Week 52 [Week 52]
The PGIC for NMPP is a 1-item questionnaire designed to assess participant's impression of change in the severity of pain when they are not menstruating.
Proportion Of Participants Who Are Better Or Much Better On PGIC For Dyspareunia At Week 52 [Week 52]
The PGIC for dyspareunia is a 1-item questionnaire designed to assess participant's impression of change in the severity of their pain during sexual intercourse.
Change From Parent Study Baseline In The Mean Dysmenorrhea Functional Impairment At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using the subject-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an e-Diary.
Change From Parent Study Baseline In The Mean NMPP Functional Impairment At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using the subject-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an e-Diary.
Change From Parent Study Baseline In The Mean Dyspareunia Functional Impairment At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using the subject-modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an e-Diary.
Change From Parent Study Baseline In Patient Global Assessment (PGA) For Function At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
The PGA for function is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities.
Change From Parent Study Baseline In PGA For Pain At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
The PGA for function is a 1-item questionnaire designed to assess participant's impression of the severity of their pain.
Proportion Of Responders Based On Their EHP-30 Pain Domain Score At Week 52 And Week 104 [Week 52 and Week 104]
Assessed using the Pain Domain of the EHP-30 questionnaire.
Change From Parent Study Baseline In Each Of The Non-Pain EHP-30 Domains (Control And Powerlessness, Social Support, Emotional Well-Being, And Self-Image) At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed using EHP-30 questionnaire.
Percent Change From Parent Study Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Assessed by dual-energy X-ray absorptiometry (DXA) scan.
Change From Parent Study Baseline In Predose Serum Concentrations Of Estradiol At Week 52 And Week 104 [Parent Study Baseline, Week 52 and Week 104]
Blood samples will be collected from participants for estradiol measurements.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 51 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Completed 24 weeks of study drug treatment and study participation in either parent study, MVT-601-3101 or MVT-601-3102.
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.

Key Exclusion Criteria:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Andalusia	Andalusia	Alabama	United States	36420
2	Scottsdale	Scottsdale	Arizona	United States	85251
3	Tucson	Tucson	Arizona	United States	85704
4	Tuscon	Tucson	Arizona	United States	85712
5	Canoga Park	Canoga Park	California	United States	91303
6	Los Angeles	Los Angeles	California	United States	70433
7	San Diego	San Diego	California	United States	92111
8	Greenwood Village	Greenwood Village	Colorado	United States	80111
9	Washington	Washington	District of Columbia	United States	20036
10	Aventura	Aventura	Florida	United States	33180
11	Fort Myers	Fort Myers	Florida	United States	33912
12	Hialeah	Hialeah	Florida	United States	33012
13	Hialeah	Hialeah	Florida	United States	33016
14	Margate	Margate	Florida	United States	33063
15	Miami	Miami	Florida	United States	33126
16	Miami	Miami	Florida	United States	33155
17	Sarasota	Sarasota	Florida	United States	34239
18	Tampa	Tampa	Florida	United States	33606
19	Atlanta	Atlanta	Georgia	United States	30312
20	Atlanta	Atlanta	Georgia	United States	30363
21	Augusta	Augusta	Georgia	United States	30909
22	Norcross	Norcross	Georgia	United States	30093
23	Idaho Falls	Idaho Falls	Idaho	United States	83404
24	Oakbrook	Oakbrook Terrace	Illinois	United States	60523
25	Park Ridge	Park Ridge	Illinois	United States	60068
26	Shawnee	Shawnee Mission	Kansas	United States	66218
27	Marrero	Marrero	Louisiana	United States	70072
28	Towson	Towson	Maryland	United States	21204
29	Saginaw	Saginaw	Michigan	United States	48602
30	Jefferson City	Jefferson City	Missouri	United States	65109
31	St. Louis	Saint Louis	Missouri	United States	63141
32	Omaha	Omaha	Nebraska	United States	68130
33	Las Vegas	Las Vegas	Nevada	United States	89113
34	Durham	Durham	North Carolina	United States	27713
35	New Bern	New Bern	North Carolina	United States	28562
36	Winston Salem	Winston-Salem	North Carolina	United States	27103
37	Akron	Akron	Ohio	United States	44313
38	Columbus	Columbus	Ohio	United States	43235
39	Englewood	Englewood	Ohio	United States	45322
40	Hershey	Hershey	Pennsylvania	United States	17033-0850
41	Columbia	Columbia	South Carolina	United States	29201
42	Chattanooga	Chattanooga	Tennessee	United States	37404
43	Memphis	Memphis	Tennessee	United States	38120
44	Beaumont	Beaumont	Texas	United States	77702
45	Corpus Christi	Corpus Christi	Texas	United States	78412
46	Dallas	Dallas	Texas	United States	75231
47	Fort Worth	Fort Worth	Texas	United States	76104
48	Houston	Houston	Texas	United States	77030
49	Houston	Houston	Texas	United States	77054
50	Irving	Irving	Texas	United States	75062
51	San Antonio	San Antonio	Texas	United States	78258
52	Sugar Land	Sugar Land	Texas	United States	77479
53	Webster	Webster	Texas	United States	77598
54	Salt Lake City	Salt Lake City	Utah	United States	84102
55	Salt Lake City	Salt Lake City	Utah	United States	84107
56	Salt Lake City	Salt Lake City	Utah	United States	84124
57	Norfolk	Norfolk	Virginia	United States	23507
58	Richmond	Richmond	Virginia	United States	23235
59	Virginia Beach	Virginia Beach	Virginia	United States	23502
60	Seattle	Seattle	Washington	United States	98105
61	Ciudad de Buenos Aires	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1128AAF
62	San Isidro	San Isidro	Buenos Aires	Argentina	B1642CKL
63	Rosario	Rosario	Santa Fe	Argentina	S2000PRB
64	Cordoba	Cordoba		Argentina	X5000JHQ
65	Sydney	Sydney	New South Wales	Australia	2000
66	Wollongong	Wollongong	NS	Australia	2522
67	Taringa	Taringa	Queensland	Australia	4068
68	Adelaide	Adelaide	South Australia	Australia	5000
69	Nedlands	Nedlands	Western Australia	Australia	6009
70	Leuven	Leuven	Flemish Brabant	Belgium	3000
71	La Louvière	La Louvière	Hainaut	Belgium	7100
72	Gent	Gent	Oost-vlaanderen	Belgium	9000
73	Brussels	Brussels		Belgium	1070
74	Passo Fundo	Passo Fundo	Rio Grande Do Sul	Brazil	99010-080
75	Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90430-001
76	Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90510-040
77	Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
78	Porto Alegre	Porto Alegre	Sao Paulo	Brazil	90035-903
79	São Bernardo do Campo	São Bernardo do Campo	Sao Paulo	Brazil	09715-090
80	São Paulo	São Paulo	Sao Paulo	Brazil	04023-062
81	Sao Paulo	São Paulo	Sao Paulo	Brazil	04266-010
82	São Paulo	São Paulo	Sao Paulo	Brazil	04708-001
83	Sao Paulo	Sao Paulo		Brazil	01317-000
84	Sofia	Sofia	Sofiya	Bulgaria	1233
85	Sofia	Sofia	Sofiya	Bulgaria	1336
86	Sofia	Sofia	Sofiya	Bulgaria	1431
87	Sofia	Sofia	Sofiya	Bulgaria	1504
88	Blagoevgrad	Blagoevgrad		Bulgaria	2700
89	Pleven	Pleven		Bulgaria	5809
90	Stara Zagora	Stara Zagora		Bulgaria	6003
91	Varna	Varna		Bulgaria	9002
92	Red Deer	Red Deer	Alberta	Canada	T4N 6V7
93	Waterloo	Waterloo	Ontario	Canada	N2J1C4
94	Victoriaville	Victoriaville	Quebec	Canada	G6P 6P6
95	Santiago	Santiago		Chile	7510186
96	Santiago	Santiago		Chile	8320143
97	Santiago	Santiago		Chile	8880465
98	Písek	Písek	Jihocesky Kraj	Czechia	397 01
99	Vodňany	Vodňany	Jihocesky	Czechia	389 01
100	Tábor	Tábor	Jihormoravsky Kraj	Czechia	390 03
101	Náchod	Náchod	Kralovehradecky	Czechia	547 01
102	Praha 10	Praha 10	Praha	Czechia	100 34
103	Praha 2	Praha 2	Praha	Czechia	128 08
104	Olomouc	Olomouc		Czechia	772 00
105	Praha 8 - Libeň	Praha 8 - Libeň		Czechia	180 81
106	České Budějovice	České Budějovice		Czechia	370 01
107	Kuopio	Kuopio	Eastern Finland	Finland	70100
108	Helsinki	Helsinki	Southern Finland	Finland	00260
109	Oulu	Oulu		Finland	90100
110	Tbilisi	Tbilisi		Georgia	0159
111	Kecskemét	Kecskemét	Bacs-kiskun	Hungary	6000
112	Pécs	Pécs	Baranya	Hungary	7624
113	Békéscsaba	Békéscsaba	Bekes	Hungary	5600
114	Gyula	Gyula	Bekes	Hungary	5700
115	Szeged	Szeged	Csongrad	Hungary	6725
116	Debrecen	Debrecen	Hajdu-bihar	Hungary	4024
117	Debrecen	Debrecen	Hajdu-bihar	Hungary	4025
118	Debrecen	Debrecen	Hajdu-bihar	Hungary	4032
119	Nyíregyháza	Nyíregyháza	Szabolcs-szatmar-bereg	Hungary	4400
120	Monserrato	Monserrato	Cagliari	Italy	9042
121	Catanzaro	Catanzaro		Italy	88100
122	Napoli	Napoli		Italy	80131
123	Pavia	Pavia		Italy	27100
124	Roma	Roma		Italy	00168
125	Remuera	Remuera	Auckland	New Zealand	1050
126	Palmerston North	Palmerston North	Manawatu-wanganui	New Zealand	4442
127	Christchurch	Christchurch		New Zealand	8013
128	Łódź	Łódź	Lodzkie	Poland	90-602
129	Lublin	Lublin	Lubelskie	Poland	20-064
130	Lublin	Lublin	Lubelskie	Poland	20-093
131	Lublin	Lublin	Lubelskie	Poland	20-632
132	Lublin	Lublin	Lubelskie	Poland	20-880
133	Warszawa	Warszawa	Mazowieckie	Poland	02-066
134	Warszawa	Warszawa	Mazowieckie	Poland	02-201
135	Warszawa	Warszawa	Mazowieckie	Poland	02-929
136	Białystok	Białystok	Podlaskie	Poland	15-224
137	Katowice	Katowice	Slaskie	Poland	40-081
138	Katowice	Katowice	Slaskie	Poland	40-301
139	Skórzewo	Skórzewo	Wielkopolskie	Poland	60-185
140	Szczecin	Szczecin	Zachodniopomorskie	Poland	71-434
141	Almada	Almada	Lisboa	Portugal	2805-267
142	Coimbra	Coimbra		Portugal	3000-075
143	Covilhã	Covilhã		Portugal	6200-251
144	Porto	Porto		Portugal	4099-001
145	Brasov	Brasov		Romania	500091
146	Bucuresti	Bucuresti		Romania	012071
147	Bucuresti	Bucuresti		Romania	022441
148	Bucuresti	Bucuresti		Romania	024091
149	București	București		Romania	20475
150	Port Elizabeth	Port Elizabeth	Eastern Cape	South Africa	6001
151	Centurion	Centurion	Gauteng	South Africa	0157
152	Roodepoort	Roodepoort	Gauteng	South Africa	1724
153	Durban	Durban	Kwazulu-natal	South Africa	4126
154	Cape Town	Cape Town	Western Cape	South Africa	7405
155	Madrid	Madrid		Spain	28041
156	Valencia	Valencia		Spain	46010
157	Kyiv	Kyiv	Kiev City	Ukraine	2232
158	Kyiv	Kyiv	Kiev City	Ukraine	4050
159	Kyiv	Kyiv	Kiev	Ukraine	1034
160	Chernivtsi	Chernivtsi		Ukraine	58001
161	Ivano-Frankivsk	Ivano-Frankivsk		Ukraine	76018
162	Kharkiv	Kharkiv		Ukraine	61052
163	Kiev	Kiev		Ukraine	3148
164	Kiev	Kiev		Ukraine	4112
165	Kyiv	Kyiv		Ukraine	04053
166	Zaporizhzhya	Zaporizhzhya		Ukraine	69063
167	Zaporizhzhya	Zaporizhzhya		Ukraine	69065
168	Zaporizhzhya	Zaporizhzhya		Ukraine	69068
169	Zaporizhzhya	Zaporizhzhya		Ukraine	69071