E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. |
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E.1.1.1 | Medical condition in easily understood language |
Hot flushes associated with menopause. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027311 |
E.1.2 | Term | Menopause flushing |
E.1.2 | System Organ Class | 100000004872 |
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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 effect of oral SJX-653 on moderate to severe VMS symptom frequency after 4 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Secondary: • Efficacy of oral SJX-653 on measures of VMS severity and frequency. • Safety and tolerability of SJX-653 • PK of SJX-653.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet the following criteria for inclusion: 1. Signed a consent form before Screening procedures begin. 2. Be a postmenopausal female, 40 to 65 years of age (inclusive) at the Screening Visit, defined as: a.Spontaneous amenorrhea for at least 12 months, OR b.6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL, OR c.6 weeks past a postsurgical bilateral oophorectomy with or without hysterectomy, All PMW must have a serum FSH >40 mIU/mL at Screening. 3. Have an average of at least 7 moderate to severe VMS per day at Baseline The following definitions for severity are used: a.Mild: Sensation of heat without sweating/damping; if at night, do not wake up but later notice damp sheets or clothing. b.Moderate: Sensation of heat with sweating/dampness, but able to continue activity; if at night, wake up because hot and/or sweating, but no action is necessary other than rearranging the bed sheets. c.Severe: Sensation of heat with sweating causing disruption of current activity; if at night, wake up hot and sweating and need to take action (eg, removing layer of clothes, open the window, or get out of bed). 4. Have a body mass index between 18 and 35 kg/m2, inclusive. 5.Have a clinical breast exam without clinically significant finding at Screening. 6.For Subjects 50-65 years old, have documentation (written or electronic report) of a satisfactory mammogram result at Screening within applicable intervals stated in local breast cancer screening guidelines. Subjects 40-49 years old require a mammogram within the same intervals. 7.Have documentation (written or electronic report) of a normal Pap smear (or equivalent cervical cytology) in combination with Human Papilloma virus (HPV) testing, or a Pap smear of no clinical significance in the opinion of the Investigator, at Screening within applicable intervals stated in local cervical cancer prevention guidelines. 8.Be willing to undergo a transvaginal ultrasound to assess endometrial thickness at Screening and at Week 4 (EOT). This is not required for subjects who have had a partial (supracervical) or full hysterectomy. 9.Have an endometrial thickness ≤4 mm by transvaginal ultrasound at Screening 10.Subjects must be willing to undergo an endometrial biopsy if they have unexplained bleeding during the study or an endometrial thickness >4 mm at the EOT Visit. An endometrial biopsy is not required for subjects who have had a partial (supracervical) or full hysterectomy.
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E.4 | Principal exclusion criteria |
1.Have clinically significant history or evidence of poorly controlled cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the Investigator or have any medical condition that requires chronic medication and that in the Investigator’s opinion, would make subjects unsuitable for participation in the study. 2.Have manifest or suspected active COVID-19 infection -Have tested +ve for presence of SARS-CoV-2 based on a RT-PCR or other validated test, or -Have clinical symptoms suggestive of COVID-19 infection, or Have to comply with quarantine requirements per local Public -Health directive 3.Have a history of diagnosis of major depressive disorder in the 3 years prior to Screening, or are on any antidepressant, anxiolytic or antipsychotic treatment with the following exceptions: -SSRIs and SNRIs treatment for mild depression and/or mild anxiety is allowed provided medication is stable and well-tolerated in the 3 months prior to the Screening Visit and does not change during study participation. -SSRIs and SNRIs for treatment of VMS are prohibited 4. Have a history of suicide ideation or attempt in the past 3 years. 5. Have a history of a sleep disorder other than insomnia due to VMS. 6. Have clinical or biochemical evidence of active hepatitis or other significant hepatic or biliary disease 7. Have any abnormal liver function tests a Screening or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2). 8. Have tested positive for human immunodeficiency virus, hepatitis B, C or E. 9. Have any gastrointestinal, liver, kidney or other disorder that would significantly interfere with the absorption, distribution, metabolism, or excretion (ADME) of drugs in the opinion of the Investigator, including surgery (eg, short bowel syndrome, gastric or intestinal bypass surgery). 10. Have a history of alcohol abuse or a history of substance abuse. 11. Smoking >10 cigarettes per day. 12.Regularly working night shifts. 13.Have a history of hypersensitivity to more than two chemical classes of drugs, or known hypersensitivity to SJX-653 or any of its excipients. 14.Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure as ≥90 mmHg, based on the median of a total of 4 to 6 readings, from 2 to 3 readings taken on at least 2 different occasions. 15.Have poorly controlled Type II diabetes mellitus as defined by a glycosylated hemoglobin (HbA1c) >8.0% despite standard care. Subjects with Type I diabetes and subjects on insulin treatment are excluded. 16.Have a history of or are on treatment for hyperthyroidism or hypothyroidism, or have abnormal thyroid tests (T3, T4, thyroid-stimulating hormone) at Screening. Subjects with subclinical hypothyroidism, and subjects on stable treatment for hypothyroidism for a least 3 months prior to Screening with normal thyroid function test results at Screening are allowed 17. Have clinically significant abnormal ECG or QT interval prolongation at Screening. 18. Have a history of endometrial hyperplasia or uterine/endometrial cancer. 19. Have current unexplained uterine bleeding. 20. Have a history of cancer prior to Screening (other than local, treated basal cell or squamous cell carcinoma). 21. Have any significant illness requiring hospitalization or emergency treatment within 4 weeks prior to the Screening Visit or during the Screening or Run-in Periods, and as determined by the Investigator. 22. Are pregnant or lactating. 23. Are taking any drugs considered moderate or strong inducers and/or inhibitors of cytochrome P450 3A4 (CYP3A4). 24.Started statin therapy less than 3 months prior to Screening, or are not on a stable and well-tolerated dose in the 3 months prior to Screening. 25. Have used any of the hormonal treatments listed in the protocol during the timeframes listed prior to the start of the Run-in Period. 26. Are taking any nonhormonal medication for treatment of VMS in the 8-week period prior to the start of the Run-in Period. 27. Have used herbal supplements or over-the-counter (OTC) medications for treatment of VMS 8 weeks prior to the start of the Run-in Period. Any other herbal supplements or TC supplements that could interfere with the study objectives require a 28-day wash-out period prior to the start of the Run-in Period. 28.Are taking any antiestrogens, selective estrogen receptor modulators, or aromatase inhibitors. 29.Are taking any antigonadotropin medication. 30.Are legally or mentally incapacitated. 31.Are not a suitable clinical study candidate per Investigator assessment. 32.Are currently participating in another drug or device clinical study or have received the last dose/device intervention in such a study within 90 days or 5 half-lives (whichever is longer) prior to the Screening Visit. 33.Have previously received SJX-653 in another clinical study. 34.Are directly involved in the conduct of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in average daily frequency of moderate to severe VMS from Baseline to Week 4. |
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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) |
Efficacy • Mean change and percent change of parameters of VMS frequency and severity Safety •Change in clinical laboratory, vital signs, and ECGs. Pharmacokinetic •Estimation of SJX-653 PK profile |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LPLV (Last Patient Last 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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |