COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003403-33/BE

NEURALIS s.a. - Anastassia Karageorgis

akarageorgis@mithra.com

2020-12-16

Completed

RCT

Randomized

Parallel

Blind label

multi-center

Treatment

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.

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.

2

NEURALIS s.a.

18

100

Georgia;Russia;Belgium;Hungary;Poland

Moderate disease at enrollment

3: Moderate disease at enrollment

10

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.

Declared number of arm (3.0) differs from found arms (2.0)

Phase 2

[{"arm_notes": "", "treatment_id": 481, "treatment_name": "Estetrol", "treatment_type": "Hormones", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "", "treatment_id": 2187, "treatment_name": "Placebo", "treatment_type": "Placebo", "pharmacological_treatment": "Placebo"}]