Covid19Phase 2NCT04801836
Estetrol (E4) for the Treatment of Patients With Confirmed SARS-COV-2 Infection
A Phase 2 study testing Estetrol monohydrate 15 mg in people with Covid19, run by NEURALIS s.a. at 25 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Estetrol monohydrate 15 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 162 participants
- Where
- 25 sitesin 4 countries
- Study dates
- 19 Nov 2020to 5 Aug 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
Show all 19Show fewer
- 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.
- Use of zanamivir or oseltamivir within 1 week prior to randomization.
- Patients who have received prior investigational or off-label agents for COVID-19. (Note: use of antivirals and corticosteroids is allowed if part of Standard of Care).
- Using methyldopa or clonidine containing antihypertensive medication.
- Hypersensitivity to the active substance of the study drug or any other components of the study drug.
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
Russia11 sites
City Clinical Hospital #15 n.a. Filatov
Moscow, 111539
State budgetary healthcare institution of Moscow "City Clinical Hospital No 52 of the Department of Healhcare of Moscow"
Moscow, 123182
State Budgetary Healthcare Institution "Clinical Infectious Disease Hospital No. 1 of the Moscow City Health Department"
Moscow, 125367
Saint-Petersburg state budgetary healthcare institution "Clinical infectious hospital n.a. S.P. Botkin"
Saint Petersburg, 191167
Saint-Petersburg state budgetary healthcare institution "Alexandrovskaya City Hospital"
Saint Petersburg, 193312
City Hospital #15
Saint Petersburg, 198205
Saint-Petersburg state budgetary healthcare institution "Pokrovskaya City Hospital"
Saint Petersburg, 199106
Saint-Petersburg state budgetary healthcare institution "City hospital No 40 of resort region"
Sestroretsk, 197706
Budgetary healthcare institution of Voronezh Region "Voronezh regional clinical hospital"
Voronezh, 394066
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
State budgetary healthcare institution of Moscow Region "Zhukovskaya City Clinical Hospital"
Zhukovskiy, 140160
Poland8 sites
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej Oddział Kardiologiczny Pododdział Kardiologii Zachowawczej
Biała Podlaska, 21-500
Zespół Opieki Zdrowotnej w Bolesławcu Oddział Chorób Wewnętrznych
Bolesławiec, 59-700
Arion Med. Sp z o.o. Zespół Opieki Zdrowotnej w Gostyninie Oddział Chorób Wewnętrznych
Gorzewo, 09-500
Samodzielny Publiczny Zakad Opieki Zdrowotnej w Pulawach Oddział Obserwacyjno-Zakaźny
Puławy, 24-100
Samodzielny Publiczny Zespół Zakładów Opieki Zdrowotnej w Staszowie Oddział Chorób Wewnętrznych
Staszów, 28-200
Wielospecjalistycznego Szpitala im. J. Strusia z Zakładem Opiekuńczo - Leczniczym SP ZOZ Oddział Chorób Wewnętrznych
Szczecin, 71-455
Szpital Matki Bożej Nieustającej Pomocy w Wołominie Oddział Chorób Wewnętrznych
Wołomin, 05-200
Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego I Oddział Chorób Zakaźnych
Wroclaw, 51-149
Hungary4 sites
Koranyi National Institute of Pulmonology
Budapest, 1121
University of Pecs Medical Center
Pécs, 7623
University of Szeged Medical Center
Szeged, 6725
Szent Borbala Korhaz
Tatabánya, 2800
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Trial to Determine the Safety and Efficacy of Estetrol (E4) for the Treatment of Patients With Confirmed SARS-COV-2 Infection
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
- Being tested
- Estetrol monohydrate 15 mg, Placebo
- Keywords
- SARs-CoV-2 infection, COVID 19 infection, Estetrol
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estetrol monohydrate 15 mgDrug
Also called E4 15 mg
One Estetrol monohydrate (E4) 15 mg tablet once per day
PlaceboDrug
One placebo tablet once per day
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Subjects will receive 15 mg E4 orally once daily for 21 consecutive days Receives: Drug: Estetrol monohydrate 15 mg |
| Placebo Arm | Placebo comparator | Subjects will receive matching placebo orally once daily for 21 consecutive days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]
Measured: At Day 28
Secondary outcomes (4)
Number of participants reaching a score of ≥6 on the WHO (0-10) scale at Day 28
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]
Measured: At Day 28
Time to recovery
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]
Measured: Up to Day 28
SARS-CoV-2 viral load
Measured: 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
AEs, Adverse events; SAEs, Serious adverse events; AESIs, Adverse events of special interest; SARs, Serious adverse reactions; SUSARs, Suspected unexpected serious adverse reactions.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2021
- Study start19 Nov 2020
- Primary completion4 Mar 2022 (estimated)
- Study completion5 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 162 participants (actual)
Sponsor and investigators
- Lead sponsor
- NEURALIS s.a.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04801836
- Sponsor's protocol ID
- MIT-Co001-C101
- Other IDs
- 2020-003403-33
- Status last verified
- May 2021
- First submitted
- 12 Mar 2021
- Last updated
- 2 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Trial to Determine the Safety and Efficacy of Estetrol (E4) for the Treatment of Patients With Confirmed SARS-COV-2 Infection
- ClinicalTrials.gov ID
- NCT04801836
- Acronym / sponsor ID
- MIT-Co001-C101
- Conditions
- Covid19
- Keywords
- SARs-CoV-2 infection, COVID 19 infection, Estetrol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 162 participants (actual)
- Lead sponsor
- NEURALIS s.a.Industry (pharma, biotech, devices)
- Study start
- 19 Nov 2020 (actual)
- Primary completion
- 4 Mar 2022 (estimated)
- Study completion
- 5 Aug 2022 (estimated)
- First posted
- 17 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Estetrol monohydrate 15 mgSubjects will receive 15 mg E4 orally once daily for 21 consecutive days |
| Placebo Arm | Placebo comparator | Drug: PlaceboSubjects will receive matching placebo orally once daily for 21 consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estetrol monohydrate 15 mgAlso: E4 15 mgOne Estetrol monohydrate (E4) 15 mg tablet once per day | Drug | Treatment Arm |
| PlaceboOne placebo tablet once per day | Drug | Placebo Arm |
Primary outcome
Percentage of participants who have recovered at Day 28
Time frame: 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]
4 secondary outcomes
Number of participants reaching a score of ≥6 on the WHO (0-10) scale at Day 28
Time frame: At Day 28
Time to recovery
Time frame: Up to Day 28
SARS-CoV-2 viral load
Time frame: 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
Time frame: 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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Estetrol monohydrate 15 mg in people with Covid19, run by NEURALIS s.a. at 25 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Russia, Poland, Hungary, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of participants who have recovered at Day 28 (time frame: At Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2021.