Assess Safety and Efficacy of Vilaprisan in Patients With Uterine Fibroids (ASTEROID 2)

A Randomized, Parallel-group, Double-blind Placebo-controlled and Open Label Active Controlled, Multi-center Study to Assess the Efficacy and Safety of Vilaprisan in Patients With Uterine Fibroids

The study is performed to assess the efficacy of Vilaprisan (BAY1002670) in patients with uterine fibroids compared to placebo and ulipristal. It is also aimed to evaluate the safety of vilaprisan in subjects with uterine fibroids. Further, data on population pharmacokinetic (PK)/ pharmacodynamic (PD) relationship for vilaprisan in subjects with uterine fibroids will be supplemented.

Study Overview

• Status: Completed
• Conditions: Leiomyoma
• Intervention / Treatment: Drug: Vilaprisan (BAY1002670); Drug: Vilaprisan (BAY1002670); Drug: Vilaprisan (BAY1002670; Drug: Vilaprisan (BAY1002670; Drug: Ulipristal; Drug: Ulipristal; Drug: Ulipristal

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
  • Kärnten
    • Villach, Kärnten, Austria, 9500
  • Steiermark
    • Graz, Steiermark, Austria, 8036
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
• Belgium
  • Bruxelles - Brussel, Belgium, 1000
  • Edegem, Belgium, 2650
  • Vlaams Brabant
    • Tienen, Vlaams Brabant, Belgium, 3300
• Bulgaria
  • Pleven, Bulgaria, 5800
  • Sofia, Bulgaria, 1606
  • Sofia, Bulgaria, 1504
  • Stara Zagora, Bulgaria, 6000
• Czech Republic
  • Brno, Czech Republic, 625 00
  • Ceske Budejovice, Czech Republic, 37001
  • Olomouc, Czech Republic, 775 20
  • Olomouc, Czech Republic, 772 00
  • Pisek, Czech Republic, 39701
  • Plzen, Czech Republic, 30708
  • Praha, Czech Republic, 13000
  • Praha 2, Czech Republic, 120 00
  • Praha 8, Czech Republic, 180 81
• Finland
  • Helsinki, Finland, 00610
  • Pori, Finland, 28500
  • Turku, Finland, 20100
• Germany
  • Berlin, Germany, 10787
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
  • Sachsen-Anhalt
    • Bernburg, Sachsen-Anhalt, Germany, 06406
    • Blankenburg, Sachsen-Anhalt, Germany, 38889
• Hungary
  • Budapest, Hungary, 1036
  • Debrecen, Hungary, 4032
  • Debrecen, Hungary, 4024
  • Szentes, Hungary, H-6600
• Italy
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41124
  • Sardegna
    • Cagliari, Sardegna, Italy, 09042
  • Sicilia
    • Catania, Sicilia, Italy, 95123
• Lithuania
  • Vilnius, Lithuania, LT-10207
  • Vilnius, Lithuania, LT-05263
  • Vilnius, Lithuania, LT-08217
• Netherlands
  • Almere, Netherlands, 1315 RA
  • Heerlen, Netherlands, 6419 PC
  • Nieuwegein, Netherlands, 3435 CM
  • Zwolle, Netherlands, 8025 AB
• Norway
  • Fredrikstad, Norway, 1605
  • Lørenskog, Norway, 1478
  • Nesttun, Norway, 5221
  • Stavanger, Norway, 4011
• Poland
  • Bialystok, Poland, 15- 224
  • Lodz, Poland, 90-602
  • Lublin, Poland, 20-093
  • Lublin, Poland, 20-632
  • Warszawa, Poland, 02-507
• Portugal
  • Coimbra, Portugal, 3000-075
  • Lisboa, Portugal, 1449-005
  • Porto, Portugal, 4202-451
• Spain
  • Barcelona, Spain, 08003
  • Valencia, Spain, 46026
  • Valencia, Spain, 46010
  • Madrid
    • Aravaca, Madrid, Spain, 28023
• Sweden
  • Stockholm, Sweden, 171 76
  • Stockholm, Sweden, 118 83
  • Umeå, Sweden, 90185
• United Kingdom
  • London, United Kingdom, N19 5NF
  • Nottingham, United Kingdom, NG7 2UH
  • Portsmouth, United Kingdom, PO6 3LY
  • London
    • Harrow, London, United Kingdom, HA1 3UJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women, 18 to 50 years of age at the time of screening
• Diagnosis of uterine fibroid(s) documented by transvaginal or abdominal ultrasound at screening with at least 1 fibroid with largest diameter >/=3.0 cm
• Heavy menstrual bleeding (HMB) >80 mL documented by menstrual pictogram (MP) in a bleeding episode during the screening period. Women who did not suffer from perceived HMB during the 3 months prior to Visit 1 due to any effective medical treatment, e.g. with a hormonal contraceptive, are not considered appropriate candidates and should not undergo further screening procedures. Women suffering from perceived HMB despite medical treatment, e.g. with a hormonal contraceptive, are appropriate candidates for further screening, if rules on stopping prior medication are followed. Heavy menstrual bleeding /HMB) > 80 mL should be documented within 10 consecutive days.
• Good general health (except for findings related to uterine fibroids) as proven by medical history, physical and gynecological examinations, and laboratory test results
• Normal or clinically insignificant cervical smear not requiring further follow-up. Human papilloma virus (HPV) testing in subjects with atypical squamous cells of undetermined significance (ASCUS) can be used as an adjunctive test. Subjects with ASCUS can be included if they are negative for high-risk HPV strains.
• An endometrial biopsy performed during the screening period, without significant histological disorder such as endometrial hyperplasia (including simple hyperplasia) or other significant endometrial pathology.
• Use of an acceptable nonhormonal method of contraception (i.e. either male condom, cap, diaphragm or sponge, each in combination with spermicide) starting at the bleeding episode following the screening visit 1 (Visit 1) until the end of the study. This is not required if safe contraception is achieved by a permanent method, such as bilateral fallopian tube blockage of the subject or vasectomy of the partner(s).

Exclusion Criteria:

• Pregnancy or lactation (less than 3 months since delivery, abortion, or lactation before start of treatment)
• Uterine fibroid with largest diameter >10.0 cm
• Hypersensitivity to any ingredient of the study drugs
• Hemoglobin values </= 6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values </=10.9 g/dL will be offered iron supplementation).
• Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug
• Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results
• Abuse of alcohol, drugs, or medicines (e.g. laxatives)
• Use of other treatments that might interfere with the conduct of the study or the interpretation of the results
• Undiagnosed abnormal genital bleeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - BAY1002670 + BAY1002670; Vilaprisan (BAY1002670) 2 mg once daily (12 weeks), Vilaprisan 2 mg once daily (12 weeks)	Drug: Vilaprisan (BAY1002670); Vilaprisan 2 mg (12 weeks), Vilaprisan 2 mg (12 weeks); Drug: Vilaprisan (BAY1002670); Placebo (12 weeks), treatment break, Vilaprisan 2 mg (12 weeks)
Experimental: Arm 2 - Placebo + BAY1002670; Placebo once daily (12 weeks), Vilaprisan 2 mg once daily (12 weeks)	Drug: Vilaprisan (BAY1002670; Placebo (12 weeks),Vilaprisan (12 weeks); Drug: Vilaprisan (BAY1002670; Vilaprisan 2 mg (12 weeks), treatment break, Vilaprisan 2 mg (12 weeks)
Experimental: Arm 3 - BAY1002670 + BAY1002670; Vilaprisan 2 mg once daily (12 weeks), treatment break, Vilaprisan 2 mg once daily (12 weeks)	Drug: Vilaprisan (BAY1002670; Placebo (12 weeks),Vilaprisan (12 weeks); Drug: Vilaprisan (BAY1002670; Vilaprisan 2 mg (12 weeks), treatment break, Vilaprisan 2 mg (12 weeks)
Experimental: Arm 4 - Placebo+BAY1002670; Placebo once daily (12 weeks), treatment break, Vilaprisan 2 mg once daily(12 weeks)	Drug: Vilaprisan (BAY1002670); Vilaprisan 2 mg (12 weeks), Vilaprisan 2 mg (12 weeks); Drug: Vilaprisan (BAY1002670); Placebo (12 weeks), treatment break, Vilaprisan 2 mg (12 weeks)
Active Comparator: Arm 5 - Ulipristal + Ulipristal; Ulipristal 5 mg once daily (12 weeks), treatment break, Ulipristal 5 mg once daily (12 weeks)	Drug: Ulipristal; Ulipristal 5 mg (12 weeks), treatment break, Ulipristal 5 mg (12 weeks); Drug: Ulipristal; Placebo (12 weeks), treatment break, Ulipristal 5 mg (12 weeks); Drug: Ulipristal; Ulipristal (12 weeks), treatment break, Placebo (12 weeks)
Active Comparator: Arm 6- Placebo + Ulipristal; Placebo once daily (12 weeks), treatment break, Ulipristal 5 mg once daily (12 weeks)	Drug: Ulipristal; Ulipristal 5 mg (12 weeks), treatment break, Ulipristal 5 mg (12 weeks); Drug: Ulipristal; Placebo (12 weeks), treatment break, Ulipristal 5 mg (12 weeks); Drug: Ulipristal; Ulipristal (12 weeks), treatment break, Placebo (12 weeks)
Active Comparator: Arm 7- Ulipristal + Placebo; Ulipristal 5 mg once daily (12 weeks), treatment break, Placebo once daily (12 weeks)	Drug: Ulipristal; Ulipristal 5 mg (12 weeks), treatment break, Ulipristal 5 mg (12 weeks); Drug: Ulipristal; Placebo (12 weeks), treatment break, Ulipristal 5 mg (12 weeks); Drug: Ulipristal; Ulipristal (12 weeks), treatment break, Placebo (12 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amenorrhea (yes/no)	Defined as no scheduled or unscheduled bleeding/spotting after end of the initial bleeding episode until the end of the respective treatment period.	From day 7 to day 84 of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of bleeding days		Up to 32 weeks
Time to onset of controlled bleeding		Up to 28 weeks
Percent change in volume of largest fibroid from baseline to end of treatment.		Baseline and up to 28 weeks
Endometrial histology	(Frequency of the following categories: benign endometrium, endometrial hyperplasia, malignant neoplasm)	Baseline and up to 40 weeks
Endometrial thickness measured by transvaginal ultrasound.		Baseline and up to 40 weeks

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Gemzell-Danielsson K, Heikinheimo O, Zatik J, Poka R, Rechberger T, Hudecek R, Petersdorf K, Ramirez F, Faustmann T, Groettrup-Wolfers E, Seitz C. Efficacy and safety of vilaprisan in women with uterine fibroids: Data from the phase 2b randomized controlled trial ASTEROID 2. Eur J Obstet Gynecol Reprod Biol. 2020 Sep;252:7-14. doi: 10.1016/j.ejogrb.2020.05.043. Epub 2020 May 31.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: May 22, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 9, 2015

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Uterine fibroids; Heavy Menstrual Bleeding
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: 17541; 2014-004221-41 (EudraCT Number)