Estetrol (E4) for the Treatment of Patients With Confirmed SARS-COV-2 Infection

NCT04801836 | Unknown Phase 2

• 2 other identifiers: MIT-Co001-C1012020-003403-33
• Study Type: interventional
• Target: 162
• Locations: 4 countries
• Sites: 25

Brief Summary

It has been reported in several research studies that men are almost twice as likely to progress to severe COVID 19 disease and die than women. Some researchers have suggested this is due to the activity of estrogen which is produced by the ovaries in pre-menopausal women. Men and post-menopausal women produce very low levels of estrogen. This study will look whether E4, a natural estrogen, can help men and post-menopausal women that are hospitalized with COVID 19 infection but for whom help breathing is not yet needed. The study has 2 parts. In Part A, 162 patients will be randomized (81 patients in the E4 treatment arm and 81 patients in the placebo treatment arm). The data collected from patients in Part A will address the primary and secondary objectives of the study. Once all patients in Part A have been randomized and Part A analysis is complete, assuming positive data, recruitment and double-blind randomization of patients will continue into Part B, unchanged, on 1:1 basis to E4 and placebo.

Conditions

Covid19

Keywords

SARs-CoV-2 infection; COVID 19 infection; Estetrol

Outcome Measures

Primary Outcomes (1)

• Percentage of participants who have recovered at Day 28

  Participants have recovered if they have reached a score ≤3 on the World Health Organization (WHO) (0-10) scale. The WHO Ordinal Scale for Clinical Improvement is as follows: 0) uninfected; 1) ambulatory, asymptomatic; 2) ambulatory, symptomatic, independent; 3) ambulatory, symptomatic, assistance needed; 4) hospitalized, no oxygen therapy; 5) hospitalized, oxygen by mask or nasal prongs; 6) hospitalized, non-invasive ventilation or high-flow oxygen; 7) hospitalized, intubation and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200; 8) hospitalized, mechanical ventilation pO2/FiO2 \<150 (SpO2/FiO2 \<200) or vasopressin; 9) hospitalized, mechanical ventilation, pO2/FiO2 \<150 and vasopressin, dialysis, or extracorporeal membrane oxygenation (ECMO); 10) dead. \[FiO2, fraction of inspired oxygen; pO2, partial pressure of oxygen; SpO2, oxygen saturation\]

  At Day 28

Secondary Outcomes (4)

• Number of participants reaching a score of ≥6 on the WHO (0-10) scale at Day 28

  At Day 28

• Time to recovery

  Up to Day 28

• SARS-CoV-2 viral load

  At Days 1, 3, 7, and 14, and end of treatment visit (on Day 23 or within 48 hours of the last dose of study drug if treatment is stopped prior to Day 21)

• Number of participants with AEs, SAEs, AESIs, SARs, SUSARs and Laboratory abnormalities as a measure of safety

  Up to end of study (on Day 28 (±2 days) or 7 days (±2 days) after the last dose of study drug if treatment is stopped prior to Day 21)

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Subjects will receive 15 mg E4 orally once daily for 21 consecutive days

Drug: Estetrol monohydrate 15 mg

Placebo Arm

PLACEBO COMPARATOR

Subjects will receive matching placebo orally once daily for 21 consecutive days.

Drug: Placebo

Interventions

Estetrol monohydrate 15 mg DRUG

One Estetrol monohydrate (E4) 15 mg tablet once per day

Also known as: E4 15 mg

Treatment Arm

Placebo DRUG

One placebo tablet once per day

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women who have not used hormone replacement therapy (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.
• Patients with SARS-CoV-2 infection confirmed by a nationally accepted RT-PCR assay 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.
• To meet the definition of moderate COVID-19, it is sufficient for a patient to have been hospitalized due to COVID-19 illness.
• Hospitalized.
• Clinical Frailty Score ≤5.
• The Clinical Frailty Scale is a nine-point global frailty scale (ranging from 1: "very fit" to 9: "terminally ill") based on clinical evaluation in the domains of mobility, energy, physical activity, and function. People scoring at 5: "mildly frail" often have more evident slowing and need help in high order Instrumental Activities of Daily Living (IADLs) (finances, transportation, heavy housework, medications). Typically, mild frailty progressively impairs shopping and walking outside alone, meal preparation and housework.
• WHO Ordinal Scale for Clinical Improvement score of 4 or 5.
• Able to provide informed consent.
• Able to comply with the study procedures as defined in this protocol.

You may not qualify if:

• Males currently receiving estrogen-based hormonal therapy.
• Current participation in another interventional clinical trial.
• Ventilated and/or in ICU.
• Any unexplained abnormal bleeding including, but not limited to, vaginal bleeding.
• Diagnosed protein C, protein S or antithrombin III deficiency or any other known inherited or acquired thrombophilic abnormalities (e.g. hyperhomocysteinemia, anti-phospholipid antibodies).
• Renal impairment (glomerular filtration rate \[GFR\] \<30 mL/min/1.73 m²).
• Presence or history of severe liver disease or liver cancer (non-malignant or malignant).
• Presence or history (including suspected diagnosis) of breast cancer.
• Presence or history (including suspected diagnosis) of estrogen-sensitive tumors (e.g. endometrial cancer).
• Patients with endometrial hyperplasia.
• Patients with severe hypoxemia at risk of endotracheal intubation.
• Immunocompromised patients
• History of stroke, acute coronary syndromes, or angina pectoris.
• Presence or history of arterial or venous thrombosis/thrombembolia (including deep vein thrombosis and pulmonary emboli).
• 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.

Sponsors & Collaborators

• NEURALIS s.a.: lead

Study Sites (25)

ERASME Hospital

Brussels, 1070, Belgium

Location

CHR Citadelle

Liège, 4000, Belgium

Location

Koranyi National Institute of Pulmonology

Budapest, 1121, Hungary

Location

University of Pecs Medical Center

Pécs, 7623, Hungary

Location

University of Szeged Medical Center

Szeged, 6725, Hungary

Location

Szent Borbala Korhaz

Tatabánya, 2800, Hungary

Location

Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej Oddział Kardiologiczny Pododdział Kardiologii Zachowawczej

Biała Podlaska, 21-500, Poland

Location

Zespół Opieki Zdrowotnej w Bolesławcu Oddział Chorób Wewnętrznych

Bolesławiec, 59-700, Poland

Location

Arion Med. Sp z o.o. Zespół Opieki Zdrowotnej w Gostyninie Oddział Chorób Wewnętrznych

Gorzewo, 09-500, Poland

Location

Samodzielny Publiczny Zakad Opieki Zdrowotnej w Pulawach Oddział Obserwacyjno-Zakaźny

Puławy, 24-100, Poland

Location

Samodzielny Publiczny Zespół Zakładów Opieki Zdrowotnej w Staszowie Oddział Chorób Wewnętrznych

Staszów, 28-200, Poland

Location

Wielospecjalistycznego Szpitala im. J. Strusia z Zakładem Opiekuńczo - Leczniczym SP ZOZ Oddział Chorób Wewnętrznych

Szczecin, 71-455, Poland

Location

Szpital Matki Bożej Nieustającej Pomocy w Wołominie Oddział Chorób Wewnętrznych

Wołomin, 05-200, Poland

Location

Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego I Oddział Chorób Zakaźnych

Wroclaw, 51-149, Poland

Location

City Clinical Hospital #15 n.a. Filatov

Moscow, 111539, Russia

Location

State budgetary healthcare institution of Moscow "City Clinical Hospital No 52 of the Department of Healhcare of Moscow"

Moscow, 123182, Russia

Location

State Budgetary Healthcare Institution "Clinical Infectious Disease Hospital No. 1 of the Moscow City Health Department"

Moscow, 125367, Russia

Location

Saint-Petersburg state budgetary healthcare institution "Clinical infectious hospital n.a. S.P. Botkin"

Saint Petersburg, 191167, Russia

Location

Saint-Petersburg state budgetary healthcare institution "Alexandrovskaya City Hospital"

Saint Petersburg, 193312, Russia

Location

City Hospital #15

Saint Petersburg, 198205, Russia

Location

Saint-Petersburg state budgetary healthcare institution "Pokrovskaya City Hospital"

Saint Petersburg, 199106, Russia

Location

Saint-Petersburg state budgetary healthcare institution "City hospital No 40 of resort region"

Sestroretsk, 197706, Russia

Location

Budgetary healthcare institution of Voronezh Region "Voronezh regional clinical hospital"

Voronezh, 394066, Russia

Location

State budgetary healthcare institution of the Yaroslavl Region "Yaroslavl regional clinical hospital of the war veterans - international center for health problems of aged people "Healthy longevity"

Yaroslavl, 150047, Russia

Location

State budgetary healthcare institution of Moscow Region "Zhukovskaya City Clinical Hospital"

Zhukovskiy, 140160, Russia

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 17, 2021
• Study Start: November 19, 2020
• Primary Completion: March 4, 2022
• Study Completion: August 5, 2022
• Last Updated: August 2, 2021

Record last verified: 2021-05

Locations

RU (11); HU (4); PL (8); BE (2)