E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vasomotor symptoms caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone-receptor positive breast cancer
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E.1.1.1 | Medical condition in easily understood language |
Hot flashes caused by anti-cancer therapy in women with, or at high risk for developing hormone-receptor positive breast cancer |
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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 | 10022457 |
E.1.2 | Term | Instability vasomotor |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020407 |
E.1.2 | Term | Hot flashes |
E.1.2 | System Organ Class | 100000004866 |
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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 |
To evaluate the efficacy of elinzanetant for the treatment of vasomotor symptoms (VMS) caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone receptor positive breast cancer |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the onset of efficacy of elinzanetant for the treatment of VMS caused by adjuvant
endocrine therapy in women with, or at high risk for developing hormone-receptor positive breast cancer.
2. To evaluate the efficacy of elinzanetant in women with, or at high risk for developing hormone receptor positive breast cancer on: sleep quality and menopause related quality of life.
3. To evaluate the safety of elinzanetant for the treatment of VMS caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone receptor positive breast cancer. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Females aged 18 to 70 years of age inclusive, at the time of signing the informed consent.
2.Women experiencing vasomotor symptoms (VMS) caused by adjuvant endocrine therapy that they are expected to use for the duration of the study
a. Tamoxifen (maximum daily dose of 20 mg) with or without the use of gonadotropin-releasing hormone (GnRH) analogues or
b. Aromatase inhibitors with or without the use of GnRH analogues
3. Women must have
a. a personal history of hormone-receptor positive breast cancer or
b. a high risk for developing breast cancer.
4. Participant has completed Hot Flash Daily Diary (HFDD) for at least 11 days during the two weeks preceding baseline visit, and participant has recorded at least 35 moderate to severe hot flash (HF) (including night-time HF) over the last 7 days that the HFDD was completed (assessed at the Baseline Visit).
5. Contraceptive use by [women except for post-menopausal women or Women of Non childbearing potential (WONCBP)] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. |
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E.4 | Principal exclusion criteria |
1.Initial diagnosis of metastatic hormone-receptor positive breast cancer (stage IV) or recurrence under adjuvant endocrine therapy of hormone-receptor positive breast cancer.
2.Current or history (except complete remission for 5 years or more prior to signing informed consent) of any malignancy, except for hormone-receptor positive breast cancer (Stage 0-III), basal and squamous cell skin tumors.
3.Surgery or non-surgical (e.g., chemotherapy, radiotherapy, immunotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent (except use of tamoxifen, aromatase inhibitors, GnRH analogues).
4. Any clinically significant prior or ongoing history of arrhythmias, heart block and QT prolongation either determined through clinical history or on electrocardiogram (ECG) evaluation.
5.Any active ongoing condition that could cause difficulty in interpreting VMS such as: infection that could cause pyrexia, pheochromocytoma, carcinoid syndrome.
6.Any unexplained vaginal bleeding.
7.Mammogram with clinically relevant malignant or suspicious findings that will require surgery, radiotherapy or chemotherapy as per local guidelines (mammogram should not be older than 12 months prior to signing informed consent). If a mammogram is not possible after partial mastectomy an ultrasound could be performed instead.
8.Disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer diagnosed based on endometrial biopsy during screening.
9.Current arterial or venous vascular event (e.g., Myocardial infarction (MI), Transient ischemic attack (TIA), stroke, deep vein thrombosis (DVT), i.e., within the last 6 months prior to signing informed consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Mean change in frequency of moderate to severe hot flash (HF) from baseline to Week 4 (assessed by hot flash daily diary [HFDD]). 2. Mean change in frequency of moderate to severe HF from baseline to Week 12 (assessed by HFDD). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Week 4. 2. Baseline to Week 12 |
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E.5.2 | Secondary end point(s) |
1. Mean change in severity of moderate to severe HF from baseline to Week 4 (assessed by HFDD). 2. Mean change in severity of moderate to severe HF from baseline to Week 12 (assessed by HFDD). 3. Mean change in frequency of moderate to severe HF from baseline to Week 1 (assessed by HFDD). 4. Mean change in frequency of moderate to severe HF from baseline over time. 5. Mean change in patient-reported outcomes measurement information system sleep disturbance short form 8b (PROMIS SD SF 8b) total score from baseline to Week 12. 6. Mean change in menopause specific quality of life scale (MENQOL) total score from baseline to Week 12. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Week 4. 2. Baseline to Week 12. 3. Baseline to Week 1. 4. Baseline to week 56. 5. Baseline to Week 12. 6. Baseline to Week 12.
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 83 |
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 |
Canada |
Israel |
Kazakhstan |
United Kingdom |
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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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The end of the study is defined as the date of the last scheduled visit of the last participant in the study globally.
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |