E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of heavy menstrual bleeding associated with uterine fibroids. |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of heavy menstrual bleeding associated with uterine fibroids. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046784 |
E.1.2 | Term | Uterine fibroids |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy objective: To demonstrate the superior efficacy versus placebo of OBE2109 alone and in combination with add-back therapy for the reduction of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.
Safety objectives: - To assess the effect of OBE2109 alone and in combination with add-back therapy versus placebo on bone mineral density. - To assess the overall safety of OBE2109 alone and in combination with add-back therapy in subjects with uterine fibroids.
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E.2.2 | Secondary objectives of the trial |
Efficacy: To demonstrate the superior efficacy of 24 weeks of OBE2109 alone and in combination with add-back therapy versus placebo on: - Incidence of amenorrhea and time to amenorrhea - Hemoglobin levels - Menstrual bleeding
To evaluate the effect of 24 weeks of OBE2109 alone and in combination with add-back therapy versus placebo on: - Pain - Uterine fibroid symptom severity and health-related quality of life - Uterus volume - Myoma volume
To evaluate the effect of 52 weeks of OBE2109 alone and in combination with add-back therapy on the above-listed assessments.
To evaluate the impact of submucosal fibroids on primary efficacy endpoint. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Premenopausal woman at screening • Body Mass Index ≥ 18 kg/m2 • Menstrual cycles ≥ 21 days and ≤ 40 days prior to starting screening • Presence of uterine fibroids • Heavy menstrual blood loss for the first eight days of two menstrual periods assessed at screening using the alkaline hematin method |
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E.4 | Principal exclusion criteria |
• The subject is pregnant or breast-feeding or is planning a pregnancy within the duration of the study • History of uterus surgery that would interfere with the study • The subject’s condition is so severe that she will require surgery within 6 months regardless of the treatment provided • Undiagnosed abnormal uterine bleeding • Significant risk of osteoporosis or history of, or known osteoporosis or other metabolic bone disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduced menstrual blood loss at 24 weeks of treatment (last 28 days prior to Week 24 visit) defined as menstrual blood loss ≤ 80 mL and ≥ 50% reduction from baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Amenorrhea assessed using the alkaline hematin method 2. Time to amenorrhea 3. Time to reduced menstrual blood loss assessed using the alkaline hematin method 4. Number of days of uterine bleeding for each 28-day interval assessed using the alkaline hematin method 5. Hemoglobin levels (Laboratory assessment) 6. Bone Mineral Density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) scan 7. Endometrial biopsy assessed by histology 8. Endometrial thickness (assessed by ultrasound) 9. Adverse events -Frequency and severity of Treatment-Emergent Adverse Events 10. Clinical laboratory assessments, ECG and vital signs -clinically significant changes from baseline in clinical laboratory assessments, ECG and vital signs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to Weeks 24 and 52 2. Up to Weeks 24 and 52 3. Up to Weeks 24 and 52 4. Up to Week 52 5. Weeks 12, 24, 36, 52, 64 6. Weeks 24, 52, 76 7. Weeks 24, 52 8. Up to Week 64 9. Up to Week 76 10. From baseline up to Week 64 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 82 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Czech Republic |
Hungary |
Latvia |
Lithuania |
Poland |
Portugal |
Romania |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the study will be defined as the date of the final clinical database lock after the last subject has completed Week 76 visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |