A Study to Assess the Effectiveness and Safety of Different Doses of ASP1707 Compared to Placebo for Endometriosis Associated Pelvic Pain

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Assess the Efficacy, Safety, and Dose-Response Relationship of ASP1707 in Subjects With Endometriosis Associated Pelvic Pain for 12 Weeks, Followed by a 12-Week Double-blind Extension Without Placebo Control, Including a 24-Week Open-Label Leuprorelin Acetate Treatment Group for Bone Mineral Density Assessment

The main objective for this study is to assess the efficacy and dose-response relationship of ASP1707 in reduction of endometriosis associated pelvic pain. The secondary objectives are to assess the safety, tolerability, Pharmacokinetics of ASP1707, dose response relationship of ASP1707 in reduction of E2 (Estradiol), 24-week efficacy of ASP1707 in reduction of endometriosis associated pain and 24-week safety and tolerability of ASP1707.

Study Overview

• Status: Completed
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Placebo; Drug: ASP1707; Drug: Leuprorelin acetate

• Study Type: Interventional
• Enrollment (Actual): 912
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Site: 1006
  • Genk, Belgium, 3600
    • Site: 1002
  • Gent, Belgium, 9000
    • Site: 1003
  • Leuven, Belgium, 3000
    • Site: 1001
  • Liege, Belgium, 4000
    • Site: 1005
• Bulgaria
  • Plovdiv, Bulgaria
    • Site: 1105
  • Sofia, Bulgaria, 1000
    • Site: 1104
  • Sofia, Bulgaria, 1330
    • Site: 1107
  • Sofia, Bulgaria, 1504
    • Site: 1106
  • Sofia, Bulgaria
    • Site: 1102
  • Stara Zagora, Bulgaria, 6000
    • Site: 1103
• Germany
  • Berlin, Germany
    • Site: 1390
  • Dresden, Germany
    • Site: 1304
  • Erlangen, Germany
    • Site: 1302
  • Karlsruhe, Germany
    • Site: 1311
  • Luebeck, Germany
    • Site: 1306
• Hungary
  • Budapest, Hungary, 1135
    • Site: 1401
  • Budapest, Hungary
    • Site: 1407
  • Debrecen, Hungary, 4012
    • Site: 1408
  • Pecs, Hungary
    • Site: 1406
  • Szekesfehervar, Hungary
    • Site: 1402
  • Szekszard, Hungary, 7100
    • Site: 1403
  • Bacs-Kiskun Megye
    • Kecskemet, Bacs-Kiskun Megye, Hungary, 6000
      • Site: 1422
• Japan
  • Aomori, Japan, 036 8203
    • Site: 2018
  • Chiba, Japan, 299 0111
    • Site: 2017
  • Fujisawa, Japan, 252 0804
    • Site: 2005
  • Hyogo, Japan, 666 0195
    • Site: 2034
  • Hyogo, Japan
    • Site: 2039
  • Hyogo, Japan
    • Site: 2040
  • Kagoshima, Japan
    • Site: 2032
  • Kanagawa, Japan, 213 8507
    • Site: 2015
  • Kanagawa, Japan
    • Site: 2035
  • Kawagoe, Japan, 350-8550
    • Site: 2013
  • Kawasaki, Japan, 210 0024
    • Site: 2029
  • Kawasaki, Japan, 212 0058
    • Site: 2024
  • Kochi, Japan, 783 8505
    • Site: 2033
  • Kumamoto, Japan, 861 8520
    • Site: 2031
  • Kurashiki, Japan, 710 0824
    • Site: 2010
  • Kyoto, Japan, 602 8566
    • Site: 2006
  • Nagano, Japan
    • Site: 2036
  • Nagano, Japan
    • Site: 2037
  • Nagano, Japan
    • Site: 2038
  • Nagaoka, Japan, 940 2085
    • Site: 2002
  • Nagasaki, Japan, 850 0003
    • Site: 2007
  • Nara, Japan, 631 0805
    • Site: 2011
  • Sapporo, Japan, 060 0001
    • Site: 2027
  • Sapporo, Japan, 060 0031
    • Site: 2001
  • Sapporo, Japan, 060 0061
    • Site: 2030
  • Tokyo, Japan, 101 0062
    • Site: 2004
  • Tokyo, Japan, 107 0052
    • Site: 2020
  • Tokyo, Japan, 113 8431
    • Site: 2014
  • Tokyo, Japan, 113 8603
    • Site: 2009
  • Tokyo, Japan, 1130033
    • Site: 2003
  • Tokyo, Japan, 141 0022
    • Site: 2028
  • Tokyo, Japan, 157 0061
    • Site: 2025
  • Tokyo, Japan
    • Site: 2016
  • Yokohama, Japan, 225 0024
    • Site: 2012
• Poland
  • Bialystok, Poland, 15-464
    • Site: 1501
  • Bialystok, Poland
    • Site: 1505
  • Gdansk, Poland
    • Site: 1512
  • Katowice, Poland, 40-724
    • Site: 1504
  • Lublin, Poland, 20-333
    • Site: 1508
  • Lublin, Poland, 20-632
    • Site: 1507
  • Warsaw, Poland
    • Site: 1509
  • Warszawa, Poland, 02-066
    • Site: 1502
  • Warzawa, Poland
    • Site: 1525
• Romania
  • Brasov, Romania
    • Site: 1604
  • Bucaresti, Romania
    • Site: 1607
  • Bucharest, Romania, 11475
    • Site: 1602
  • Bucuresti, Romania
    • Site: 1601
  • Bucuresti, Romania
    • Site: 1606
  • Targu Mures, Romania
    • Site: 1603
• Ukraine
  • Bucuresti, Ukraine
    • Site: 1701
  • Bucuresti, Ukraine
    • Site: 1702
  • Bucuresti, Ukraine
    • Site: 1705
  • Bucuresti, Ukraine
    • Site: 1707
  • Donetsk, Ukraine
    • Site: 1713
  • Donetsk, Ukraine
    • Site: 1716
  • Kyiv, Ukraine
    • Site: 1708
  • Targu Mures, Ukraine
    • Site: 1703
  • Zaporizhzhya, Ukraine
    • Site: 1717
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Site: 1807
  • Norwich, United Kingdom, NR47UY
    • Site: 1804
  • Sheffield, United Kingdom, S10 2SF
    • Site: 1808
  • Southampton, United Kingdom, SO16 5YA
    • Site: 1806

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pre menopausal female adults with confirmed length and regular menstrual cycle
• Surgically diagnosed endometriosis
• Moderate to severe endometriosis related pain

Exclusion Criteria:

• Hormonal contraceptives or other drugs with effects on gynecological endocrinology
• Surgery for endometriosis within the 4 weeks prior to entry
• Uterine myoma
• Abnormal vaginal bleeding
• Hysterectomy or bilateral oophorectomy
• Pelvic infection
• Relevant abnormalities at gynecological exam at screening
• Disease with chronic abdominal pain of non-endometriosis origin
• Pituitary adenoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Applicable to first 12 week period (Part One); subjects in this arm will be randomized to one of the ASP1707 dose levels for the second 12 week period (Part Two)	Drug: Placebo; Oral
Experimental: ASP1707 lowest dose; Subjects in this arm will be dosed with ASP1707 once daily for a total of 12 weeks (Part One) and continue taking the assigned dose for a further 12 weeks during the extension phase of the study (Part Two) for a total of 24 weeks	Drug: ASP1707; Oral
Experimental: ASP1707 low dose; Subjects in this arm will be dosed with ASP1707 once daily for a total of 12 weeks (Part One) and continue taking the assigned dose for a further 12 weeks during the extension phase of the study (Part Two) for a total of 24 weeks	Drug: ASP1707; Oral
Experimental: ASP1707 medium dose; Subjects in this arm will be dosed with ASP1707 once daily for a total of 12 weeks (Part One) and continue taking the assigned dose for a further 12 weeks during the extension phase of the study (Part Two) for a total of 24 weeks	Drug: ASP1707; Oral
Experimental: ASP1707 high dose; Subjects in this arm will be dosed with ASP1707 once daily for a total of 12 weeks (Part One) and continue taking the assigned dose for a further 12 weeks during the extension phase of the study (Part Two) for a total of 24 weeks	Drug: ASP1707; Oral
Active Comparator: Leuprorelin acetate; Subjects in this arm will be treated with leuprorelin acetate for a total of 24 weeks	Drug: Leuprorelin acetate; subcutaneous; Other Names: Prostap® SR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to the end of 12 weeks treatment of pain score for overall pelvic pain	Baseline & Week 12
Change from baseline to the end of 12 weeks treatment of pain score for dysmenorrhea	Baseline & Week 12
Change from baseline to the end of 12 weeks treatment of pain score for non-menstrual pelvic pain	Baseline & Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to the end of 24 weeks treatment of pain score for overall pelvic pain		Baseline & Week 24
Change from baseline to the end of 24 weeks treatment of pain score for dysmenorrhea		Baseline & Week 24
Change from baseline to the end of 24 weeks treatment of pain score for non-menstrual pelvic pain		Baseline & Week 24
Change from baseline to the end of treatment (EoT) of the dyspareunia score		Baseline, Week 12 & Week 24
Occurrence of response at the EoT for pain score for overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain and dyspareunia		Week 12 & Week 24
Change from baseline to the EoT of the mean scores of the modified Biberoglu and Behrman (B&B) symptom and sign domains		Baseline, Week 12 & Week 24
Change from baseline to the EoT of the use of protocol defined rescue medication		Baseline, Week 12 & Week 24
Change from baseline to the EoT of the mean Pain Interference score of the Brief Pain Inventory		Baseline, Week 12 & Week 24
Patient Global Impression of Change (PGIC) at the End of Treatment		Week 12 & Week 24
Change from baseline to the EoT in the Endometriosis Health Profile (EHP)-5 score		Baseline, Week 12 & Week 24
Change from baseline to the EoT of the Female Sexual Function Index (FSFI) score (sexual well-being)		Baseline, Week 12 & Week 24
Change from baseline to the EoT of the Beck's Depression Inventory (BDI)-II score		Baseline, Week 12 & Week 24
Change from baseline to the EoT in the EuroQol (EQ-5D-5L) score		Baseline, Week 12 & Week 24
Safety and tolerability of ASP1707 measured by Adverse Events (AEs), bleeding patterns, Bone Mineral Density (BMD)		Up to Week 42
Pharmacodynamic profile of ASP1707 measured by Serum Estradiol (E2) levels		Up to Week 26
Pharmacokinetic profile of ASP1707	Both CL/F, V/F, AUCtau, Cmax, Ctrough	Up to Week 24

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Investigators: Study Chair: Clinical Study Manager, Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• D'Hooghe T, Fukaya T, Osuga Y, Besuyen R, Lopez B, Holtkamp GM, Miyazaki K, Skillern L. Efficacy and safety of ASP1707 for endometriosis-associated pelvic pain: the phase II randomized controlled TERRA study. Hum Reprod. 2019 May 1;34(5):813-823. doi: 10.1093/humrep/dez028.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2012
• Primary Completion (Actual): May 13, 2015
• Study Completion (Actual): July 30, 2015

Study Registration Dates

• First Submitted: December 18, 2012
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (Estimated): January 14, 2013

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Placebo-controlled; Double-blind; Pelvic pain; Endometriosis; Phase 2; ASP1707
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pain; Neurologic Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endometriosis; Pelvic Pain; Antineoplastic Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: 1707-CL-0011; 2012-002791-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR