Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with moderate COVID-19. MedDRA version: 23.0 Level: LLT Classification code 10053983 Term: Corona virus infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Estetrol (E4)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Estetrol
CAS Number: 2055649-81-3
Current Sponsor code: E4
Other descriptive name: Estetrol monohydrate
Concent
Sponsors
NEURALIS s.a.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Postmenopausal women who have not used HRT (including oral, transdermal, topical, or vaginal preparations) within 1 year prior to study start. Menopause is defined as women who have at least 12 months of spontaneous amenorrhea without another medical cause. OR Men = 18 years of age who are willing to use adequate contraception from Screening until 4 weeks after the last dose of study treatment. 2. Patients with SARS-CoV-2 infection confirmed by a nationally accepted RT-PCR and moderate COVID-19. Patients with a strong clinical suspicion of moderate COVID-19 and a positive point-of-care test for viral infection can also be entered while the result of a nationally accepted RT-PCR assay is awaited; if the RT-PCR assay result is negative, the treatment must be stopped and the patient must be discontinued from the study. The definition of moderate COVID-19 is: i. Positive testing by standard RT-PCR assay. ii. Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness (including fever, cough, anosmia, dysgeusia, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms) or shortness of breath with exertion. iii. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate =20 breaths per minute, heart rate =90 beats per minute. iv. No clinical signs indicative of severe or critical illness (i.e. need for ventilation or ICU admission). 3. Hospitalized. 4. Clinical Frailty Score =5. 5. World Health Organization (WHO) Ordinal Scale for Clinical Improvement score of 4 or 5. 6. Able to provide IC. 7. Able to comply with the study procedures as defined in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 81 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 81
Exclusion criteria
Exclusion criteria: 1. Males currently receiving estrogen-based hormonal therapy. 2. Current participation in another interventional clinical trial. 3. Ventilated and/or in ICU. 4. Any unexplained abnormal bleeding including, but not limited to, vaginal bleeding. 5. Diagnosed protein C, protein S or antithrombin III deficiency or any other known inherited or acquired thrombophilic abnormalities (e.g. hyperhomocysteinemia, anti-phospholipid antibodies). 6. Renal impairment (glomerular filtration rate <30 mL/min/1.73 m²). 7. Presence or history of severe liver disease or liver cancer (non-malignant or malignant) 8. Presence or history (including suspected diagnosis) of breast cancer. 9. Presence or history (including suspected diagnosis) of estrogen-sensitive tumors (e.g endometrial cancer) 10. Patients with endometrial hyperplasia. 11. Patients with severe hypoxemia at risk of endotracheal intubation. 12. Immunocompromised patients 13. History of stroke, acute coronary syndromes, or angina pectoris. 14. Presence or history of arterial or venous thrombosis/ thromboembolia (including deep vein thrombosis and pulmonary emboli). 15. Patients with any condition, including findings in the patients' medical history or in the screening study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for the participation of the patient into the study or that could interfere with the study objectives, conduct or evaluation, including patients with suspected genital cancer or suspected breast cancer and patients with increased risk of development of venous thrombosis/ thromboembolia for reasons other than COVID 19 disease. 16. Use of zanamivir or oseltamivir within 1 week prior to randomization. 17. Patients who have received prior investigational or off-label agents for COVID-19. (Note: use of antivirals and corticosteroids is allowed if part of SoC). 18. Using methyldopa or clonidine containing antihypertensive medication. 19. Hypersensitivity to the active substance of the study drug or any other components of the study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the ability of E4 to improve the percentage of patients who recover by Day 28 compared to placebo in those with confirmed SARS-CoV-2 infection who are hospitalized with moderate COVID-19 (i.e. not on high flow oxygen or mechanical ventilation).;Secondary Objective: • To evaluate and compare the efficacy of E4 versus placebo treatment to prevent severe COVID-19 disease or worsening COVID-19 disease in patients with confirmed SARS-CoV-2 infection who are hospitalized with moderate COVID-19 (i.e. not on high flow oxygen or mechanical ventilation). • To assess the ability of E4 to improve the time to recovery compared to placebo in patients with confirmed SARS-CoV-2 infection who are hospitalized with moderate COVID-19 (i.e. not on high flow oxygen or mechanical ventilation). • Assess changes in viral load between the E4 and placebo groups. • To assess the general safety and tolerability of E4 compared to placebo when administered to patients with confirmed SARS-CoV-2 infection who are hospitalized with moderate COVID-19 (i.e. not on high flow oxygen or mechanical ventilation).;Primary end point(s): The primary endpoint for this trial is the improvement in COVID-19 between the placebo and E4 groups measured by the percentage of patients recovered at Day 28. Recovery will be defined as reaching a score of =3 on the WHO (0-10) scale.;Timepoint(s) of evaluation of this end point: Day 28 (±2 days) or 7 days (±2 days) after the last dose of study drug if treatment is stopped prior to Day 21. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The percentage of patients reaching a score of WHO ordinal scales (0-10) of =6 at 28 days. 2. The improvement in time to recovery between the placebo and E4 groups (=3 on the WHO (0-10) scale). 3. Changes in viral load between the E4 and placebo groups.;Timepoint(s) of evaluation of this end point: • WHO Ordinal Scale for Clinical Improvement score will be recorded daily at the same time each day (±3 hours) at Screening, on Treatment Days 1-21 whilst the patient is hospitalized and at the End of Treatment and End of Study visits. • Oropharyngeal swabs for viral load assessment will be taken on Treatment Day 1 (immediately before taking the dose of study drug), on Days 3, 7, and 14 when the patient is in hospital, and at the End of Treatment visit. | — |
Countries
Belgium, Georgia, Hungary, Poland, Russian Federation
Contacts
Public ContactAnastassia Karageorgis
NEURALIS s.a.
Outcome results
None listed