Covid19Phase 2NCT04922957

A Phase 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study, Evaluating Efficacy and Safety of Allocetra-OTS in Patients With Severe or Critical COVID-19 With Associated Acute Respiratory Distress Syndrome (ARDS)

A Phase 2 study testing ALLOCETRA-OTS in people with Covid19, run by Enlivex Therapeutics Ltd. at 1 site in Israel.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

This is a Phase 2b multi-center, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of intravenous (IV) Allocetra-OTS 10x10^9 cells vs placebo (1:1) in adult hospitalized patients with severe or critical Coronavirus Disease 2019 (COVID-19) with associated acute respiratory distress… Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Covid19
What is being tested?: ALLOCETRA-OTS
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 12 participants
Where: 1 siteIsrael
Study dates: 1 Sep 2021to 11 Mar 2024
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 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female >18 and <85 years of age.
Laboratory confirmation of SARS-CoV-2 infection by RT-PCR from any diagnostic sampling source.
Patient hospitalized due to COVID-19 within 7 days prior to enrollment, meeting the criteria for severe or critical COVID-19 as follows:
Severe COVID-19 - defined as shortness of breath at rest, or respiratory distress, or RR ≥30 per minute, or SpO2≤93% on room air at sea level.
Critical COVID-19 - defined as respiratory failure, requiring at least one of the following: oxygen delivered by high-flow nasal cannula or noninvasive positive pressure ventilation.
Patient with mild to moderate ARDS:

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100< PaO2/FiO2 ≤300; based on the Berlin Definition of ARDS
148< SpO2/FiO2 ≤315; based on the Kigali modification for ARDS
If available, PaO2 will be obtained, otherwise, SpO2 will be used for ARDS assessment.
Signed written informed consent by the patient.
Women and men who are of childbearing potential, willing to use acceptable contraceptive measures during 4 weeks from enrollment.

Who cannot join

Patient on IMV/ECMO.
Woman who is pregnant or breastfeeding.
Patient with weight <50 kg or >120 kg or BMI >40 kg/m^2.
Patient with stage 4 or 5 chronic kidney disease or estimated glomerular filtration rate <30 mL/min.
Patient with an active malignant tumor (diagnosed or on active treatment for the past 6 months).
Patient who is participating in other concurrent interventional clinical trials or has been treated with any experimental agents within 30 days prior to enrollment.

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Patient who based on their medical history and receipt of therapies that would suggest infection, has suspected serious, active bacterial (including a suspected clinical diagnosis of current active tuberculosis [TB] or, if known, latent TB treated for less than 4 weeks with appropriate anti-TB therapy per institutional guidelines), fungal, or viral (including, but not limited to, active HBV, HCV, or HIV/AIDS) infection.
Patient with known immunocompromised state or immunosuppressive medications taken for indications other than SARS-CoV-2 as follows:
Prednisone or equivalent to a dose >10 mg/day, methotrexate >15 mg/week, within the last 60 days. cyclophosphamide, cyclosporine A (unless as ophthalmic formulation), leflunomide/teriflunomide (unless as monotherapy), tacrolimus (unless as a topical formulation), everolimus, temsirolimus, or azathioprine, in the last 60 days;
Methylprednisolone, dexamethasone, cortisone, or betamethasone for more than 7 days within the last 28 days or within 5 half-lives, whichever is longer;
Chemotherapy in the last 3 months;
Mycophenolate mofetil (MMF) or sirolimus for solid organ transplant or bone marrow transplant;
Thalidomide within the last 72 hours.
Anti-tumor necrosis factor (TNF) agents, interleukin (IL)-1 receptor antagonists (IL-1-RA), CTLA-4 fusion proteins, anti-CD20, anti-CD52, anti-IL-2, anti-IL-6R, anti-IL-12/23, anti-B-cell activation factor (BAFF) or integrin inhibitor agents within the last 8 weeks.
Patient with known New York Heart Association (NYHA) class III and IV heart failure or unstable angina, ventricular arrhythmias, ischemic heart disease, or myocardial infarction within 6 months prior to diagnosis of COVID-19.
Patient with known active upper gastrointestinal (GI) tract ulceration or hepatic dysfunction including but not limited to biopsy-proven cirrhosis; end-stage cirrhosis (Child Pugh Class C); portal hypertension; episodes of past upper GI bleeding attributed to portal hypertension; or prior episodes of hepatic failure, encephalopathy, or coma.
Patient with known idiopathic pulmonary fibrosis.
Patient with chronic respiratory disease requiring home oxygen therapy on a regular basis for more than 6 hours per day.
Patient with known chronic obstructive pulmonary disease GOLD 4 (forced expiratory volume in one second <30% predicted).
Patient with any medical, psychiatric or substance abuse condition, concurrent medical therapies, or abnormal laboratory values that in the opinion of the site Investigator may influence response to study product, or interfere with the study assessments.
Patient with GCS <13 with verbal score <5.
Patient with hemoglobin <8 g/dL.
Patient with history of chronic liver disease, evidence of acute cholangitis or cholecystitis. Patients with at least one of the following:
ALT or AST >10xULN (upper limit of normal)
Bilirubin >5xULN
Combination of ALT/AST >7xULN and elevated direct bilirubin >ULN
Patient with known history of transfusion reactions, hemolytic anemia, or repetitive allergic reaction.
Patient with previous history of organ allograft or stem cell transplantation.

Trial locations and contacts

1 site in 1 country.

Israel1 site

Hadassah Ein Kerem Medical Center
Jerusalem

Other trials in Israel

About this study

Read the detailed description

Severe and critical COVID-19 are defined as follows:

Severe COVID-19: shortness of breath at rest, or respiratory distress, or respiratory rate (RR) ≥30 per minute, or SpO2 ≤93% on room air at sea level.

Critical COVID-19: respiratory failure, requiring at least one of the following: oxygen delivered by high-flow nasal cannula or noninvasive positive pressure ventilation.

After a patient has signed the informed consent form (ICF), and after confirmation that the patient meets all eligibility criteria, the patient will be enrolled in the study. The two subpopulations, severely ill and critically ill patients, will be randomized 1:1 into the active treatment and placebo groups via two separate randomizations schemes.

Study treatment (Investigational Product or placebo) administration will occur on Day 1 as close as possible to and no later than 48 hours from randomization. Assessments, performed on Day 1 prior to study treatment administration, will be considered as baseline assessments.

Patients will be followed for efficacy and safety through 6 months. Following study treatment administration, patients will be assessed daily for a period of 7 days. The next visits are planned to occur on Days 14, 28 and 60. A safety follow-up phone call will be scheduled to occur 6 months post study treatment. Hospitalized patients will be monitored on a daily basis until discharge or up to 60 days post study treatment administration.

Blood samples for safety assessment will be analyzed locally as per institutional guidelines.

Additional blood samples will be collected for potential exploratory analyses. Such biomarker analyses will be performed centrally as per Sponsor requirements.

Patients who drop out within the interval between the randomization and study treatment administration will be replaced to keep the originally planned sample size.

The trial will include periodic and ad-hoc Data Safety Monitoring Board (DSMB) review during the study period.

Conditions: Covid19
Being tested: ALLOCETRA-OTS, Placebo
Keywords: Cell therapy, Allocetra-OTS
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ALLOCETRA-OTSDrug
Also called Cell based therapy, Apoptotic cells
The product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.
PlaceboOther
Ringer's lactate solution

Study groups in NCT04922957
Study group	Role	What they receive
Placebo	Placebo comparator	Ringer's lactate solution Receives: Other: Placebo
ALLOCETRA-OTS	Experimental	Single IV dose of Allocetra-OTS containing 10x10^9 cells Receives: Drug: ALLOCETRA-OTS

What is being measured

The primary outcome is the main question the study is designed to answer.

Time (days) to improvement
The first day, during the period of 28 days post study treatment, when a patient reached the score of 6, 7 or 8 on the 8-point ordinal scale. If no improvement is reached by Day 28, the patient will be assigned a maximal score of 29.
The 8-point ordinal scale of the clinical severity status scores is as follows:
Death=1; Hospitalized, on IMV or ECMO=2; Hospitalized, on noninvasive ventilation or high-flow oxygen devices=3; Hospitalized, requiring supplemental oxygen by mask or nasal canula=4; Hospitalized, not requiring supplemental oxygen=5; Hospitalized, not requiring supplemental oxygen and not requiring ongoing inpatient medical care=6; Not hospitalized, limitations on activities=7; Not hospitalized, no limitations on activities=8.
Measured: 28 days
Support by IMV/ECMO
If required during the period of 28 days post study treatment, a patient will be assigned the maximal score of 29.
Measured: 28 days
Mortality
Mortality by Day 28 post study treatment administration. Deceased patients will be assigned the maximal score of 29.
Measured: 28 days

Secondary outcomes (6)

Time (days) to improvement, defined as the first day, during a period of 28 days and 60 days post study treatment administration, when the patient reached the score of 6, 7 or 8 on the 8-point ordinal scale.
Measured: 60 days
All-cause mortality during the period of 28 days and 60 days.
Measured: 60 days
Proportion of patients alive and free of respiratory failure, defined as need for IMV, ECMO, noninvasive ventilation, or high-flow nasal cannula oxygen delivery on Days 28 and 60.
Measured: 60 days
Cumulative number of vasopressor-free days during the period of 28 days and 60 days.
Measured: 60 days
Cumulative number of days in the hospital during the period of 28 days and 60 days.
Measured: 60 days
Cumulative number of days in the ICU or Intermediate Care Unit (IMU) during the period of 28 days and 60 days.
Measured: 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 202111 Mar 2024

First posted11 Jun 2021
Study start1 Sep 2021
Primary completion1 Apr 2022
Study completion11 Mar 2024

Why it stopped: strategic reprioritization

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: Sequential
Model description: 152 patients will be allocated in a 1:1 ratio between the 2 cohorts: 1. Placebo 2. Single Intravenous (IV) dose of Allocetra-OTS (10x10\^9 cells)
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04922957
Sponsor's protocol ID: ENX-CL-03-002
Status last verified: Aug 2022
First submitted: 9 Jun 2021
Last updated: 13 Mar 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Patient data will not contain any information which would make the patient identifiable. Data will be processes and shared using patient study number only.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Covid19 trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study, Evaluating Efficacy and Safety of Allocetra-OTS in Patients With Severe or Critical COVID-19 With Associated Acute Respiratory Distress Syndrome (ARDS)
ClinicalTrials.gov ID: NCT04922957
Acronym / sponsor ID: ENX-CL-03-002
Conditions: Covid19
Keywords: Cell therapy, Allocetra-OTS
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: strategic reprioritization
Enrolment: 12 participants (actual)
Lead sponsor: Enlivex Therapeutics Ltd.Industry (pharma, biotech, devices)
Study start: 1 Sep 2021 (actual)
Primary completion: 1 Apr 2022 (actual)
Study completion: 11 Mar 2024 (actual)
First posted: 11 Jun 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.

Detailed description

Severe and critical COVID-19 are defined as follows:

Severe COVID-19: shortness of breath at rest, or respiratory distress, or respiratory rate (RR) ≥30 per minute, or SpO2 ≤93% on room air at sea level.

Critical COVID-19: respiratory failure, requiring at least one of the following: oxygen delivered by high-flow nasal cannula or noninvasive positive pressure ventilation.

Blood samples for safety assessment will be analyzed locally as per institutional guidelines.

Additional blood samples will be collected for potential exploratory analyses. Such biomarker analyses will be performed centrally as per Sponsor requirements.

Patients who drop out within the interval between the randomization and study treatment administration will be replaced to keep the originally planned sample size.

The trial will include periodic and ad-hoc Data Safety Monitoring Board (DSMB) review during the study period.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: 152 patients will be allocated in a 1:1 ratio between the 2 cohorts: 1. Placebo 2. Single Intravenous (IV) dose of Allocetra-OTS (10x10^9 cells)

Arm	Type	Receives
Placebo	Placebo comparator	Other: PlaceboRinger's lactate solution
ALLOCETRA-OTS	Experimental	Drug: ALLOCETRA-OTSSingle IV dose of Allocetra-OTS containing 10x10^9 cells

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Male and female >18 and <85 years of age.
Laboratory confirmation of SARS-CoV-2 infection by RT-PCR from any diagnostic sampling source.
Patient hospitalized due to COVID-19 within 7 days prior to enrollment, meeting the criteria for severe or critical COVID-19 as follows:
Patient with mild to moderate ARDS:
Signed written informed consent by the patient.

Key exclusion criteria (28 listed)

Patient on IMV/ECMO.
Woman who is pregnant or breastfeeding.
Patient with weight <50 kg or >120 kg or BMI >40 kg/m^2.
Patient with stage 4 or 5 chronic kidney disease or estimated glomerular filtration rate <30 mL/min.
Patient with an active malignant tumor (diagnosed or on active treatment for the past 6 months).

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
ALLOCETRA-OTSAlso: Cell based therapy, Apoptotic cellsThe product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.	Drug	ALLOCETRA-OTS
PlaceboRinger's lactate solution	Other	Placebo

Primary outcome

Time (days) to improvement
Time frame: 28 days
The first day, during the period of 28 days post study treatment, when a patient reached the score of 6, 7 or 8 on the 8-point ordinal scale. If no improvement is reached by Day 28, the patient will be assigned a maximal score of 29. The 8-point ordinal scale of the clinical severity status scores is as follows: Death=1; Hospitalized, on IMV or ECMO=2; Hospitalized, on noninvasive ventilation or high-flow oxygen devices=3; Hospitalized, requiring supplemental oxygen by mask or nasal canula=4; Hospitalized, not requiring supplemental oxygen=5; Hospitalized, not requiring supplemental oxygen and not requiring ongoing inpatient medical care=6; Not hospitalized, limitations on activities=7; Not hospitalized, no limitations on activities=8.
Support by IMV/ECMO
Time frame: 28 days
If required during the period of 28 days post study treatment, a patient will be assigned the maximal score of 29.
Mortality
Time frame: 28 days
Mortality by Day 28 post study treatment administration. Deceased patients will be assigned the maximal score of 29.

6 secondary outcomes

Time (days) to improvement, defined as the first day, during a period of 28 days and 60 days post study treatment administration, when the patient reached the score of 6, 7 or 8 on the 8-point ordinal scale.
Time frame: 60 days
All-cause mortality during the period of 28 days and 60 days.
Time frame: 60 days
Proportion of patients alive and free of respiratory failure, defined as need for IMV, ECMO, noninvasive ventilation, or high-flow nasal cannula oxygen delivery on Days 28 and 60.
Time frame: 60 days
Cumulative number of vasopressor-free days during the period of 28 days and 60 days.
Time frame: 60 days
Cumulative number of days in the hospital during the period of 28 days and 60 days.
Time frame: 60 days
Cumulative number of days in the ICU or Intermediate Care Unit (IMU) during the period of 28 days and 60 days.
Time frame: 60 days

Results and safety

The study was stopped early (reason given: strategic reprioritization). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
Individual participant dataSharing planned: No. Patient data will not contain any information which would make the patient identifiable. Data will be processes and shared using patient study number only.

Related trials for Covid19

RecruitingObservational study
Viral Infections in Healthy and Immunocompromised Hosts
Anogenital Herpes, COVID-19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
RecruitingPhase 4
A Study to Investigate the Immunogenicity and Safety of mRNA COVID-19 Variant-containing Formulations
SARS-CoV-2
Not yet recruitingPhase 2
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Long COVID, COVID-19 (SARS-CoV-2 Infection)
Active, not recruitingObservational study
NCI COVID-19 in Cancer Patients, NCCAPS Study
COVID-19 Infection, Hematopoietic and Lymphatic System Neoplasm

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.

Oren Hershkovitz, PhD study director

Enlivex Therapeutics R&D

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ALLOCETRA-OTS in people with Covid19, run by Enlivex Therapeutics Ltd. at 1 site in Israel.

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 28 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: stopped early, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. 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?

The study was stopped early (reason given: strategic reprioritization). 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?

Time (days) to improvement (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04922957.

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 13 Mar 2024.