Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 3)

Study Overview
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Brief Summary
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The primary objective of this study was to show superiority in the treatment of HMB of vilaprisan in subjects with uterine fibroids compared to placebo. The secondary objectives of this study were to additionally evaluate the efficacy and safety of vilaprisan in subjects with uterine fibroids.

Official Title
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A Randomized, Parallel-group, Double-blind and Open-label Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Vilaprisan in Subjects With Uterine Fibroids

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Drug: Vilaprisan (BAY1002670)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women, 18 years or older in good General health Diagnosis of uterine fibroid(s) documented by ultrasound at screening with at least 1 fibroid with largest Diameter ≥ 30 mm and < 120 mm Heavy menstrual bleeding (HMB) in at least 2 bleeding periods during the Screening period each with blood loss volume of >80.00 mL documented by alkaline hematin (AH) method 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 non-hormonal method of contraception (ie, either male condom, cap, diaphragm or sponge, each in combination with spermicide) starting at Visit 1 until the end of the study Exclusion Criteria: Pregnancy or lactation (less than 3 month since delivery, abortion, or lactation before start of Treatment) Hypersensitivity to any ingredient of the study drug Any condition requiring immediate blood transfusion Laboratory values outside inclusion range before randomization and considered as clinically relevant. Any diseases, conditions, or medications 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 (eg, laxatives) Use of other treatments that might interfere with the conduct of the study or the interpretation of the results Undiagnosed abnormal genital bleeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vilaprisan (A1)<br>Vilaprisan (2 mg) in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | Drug: Vilaprisan (BAY1002670)<br>* 2 mg of Vilaprisan once daily up to 2 x 12 weeks<br>Drug: Placebo<br>* Matching placebo was administered to group B1 and B2.<br>|
| Experimental: Vilaprisan (A2)<br>Vilaprisan (2 mg) in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks without a break. | Drug: Vilaprisan (BAY1002670)<br>* 2 mg of Vilaprisan once daily up to 2 x 12 weeks<br>|
| Experimental: Placebo+Vilaprisan (B1)<br>Placebo in treatment period 1 for 12 weeks, and vilaprisan (2 mg) in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | Drug: Vilaprisan (BAY1002670)<br>* 2 mg of Vilaprisan once daily up to 2 x 12 weeks<br>Drug: Placebo<br>* Matching placebo was administered to group B1 and B2.<br>|
| Experimental: Vilaprisan+Placebo (B2)<br>Vilaprisan (2 mg) in treatment period 1 for 12 weeks and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | Drug: Vilaprisan (BAY1002670)<br>* 2 mg of Vilaprisan once daily up to 2 x 12 weeks<br>Drug: Placebo<br>* Matching placebo was administered to group B1 and B2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Amenorrhea | Amenorrhea was defined as menstrual blood loss (MBL) <2 mL during the last 28 days of treatment measured by the alkaline hematin (AH) method. | The last 28 days of treatment period 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Heavy Menstrual Bleeding (HMB) Response | HMB response was defined as MBL <80 mL during the last 28 days of treatment and >50% reduction from baseline based on AH-method. | The last 28 days of treatment period 1 and treatment period 2 | 
| Time to Onset of Amenorrhea | Onset of amenorrhea was defined by the first day for which the MBL for all subsequent 28-day periods up to the end of a treatment period was < 2 mL (amenorrhea defined similar to primary endpoint). | In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks) | 
| Time to Onset of Controlled Bleeding | Onset of controlled bleeding was defined by the first day for which the MBL for all subsequent 28-day periods up to the end of a treatment period was <80.00 mL based on AH-method. | In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks) | 
| Number of Participants With Absence of Bleeding (Spotting Allowed) | Absence of bleeding was defined as no scheduled or unscheduled bleeding (spotting allowed) during the last 28 days of a treatment period based on subjects' daily responses to the Uterine Fibroid Daily Bleeding Diary (UF-DBD). | The last 28 days of treatment period 1 and treatment period 2 | 
| Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Number of participants with endometrial histology findings, e.g. benign endometrium, Malignant Neoplasm, Hyperplasia WHO 2014, no atypia or Hyperplasia WHO 2014, atypia and Endometrial Polyps. | Up to 2 weeks after end of treatment | 
| Change From Baseline of Endometrial Thickness | Ultrasound examinations were performed. Endometrial thickness was measured in the medio-sagittal section as double-layer in millimeters. Summary statistics for change from baseline in endometrial thickness was provided in below table. | Treatment phase (up to 2 weeks after end of treatment) and follow-up phase (starts on the day after the end of the treatment until the last study visit [up to approximately 2 years]) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heavy menstrual bleeding