Covid19Phase 1NCT04659304
Study Evaluating Safety and Tolerability of Allocetra-OTS in Patients With COVID-19
A Phase 1 study testing Allocetra-OTS in people with Covid19, run by Enlivex Therapeutics Ltd..
Trial summary
Phase 1b, multi-center, open label, sequential dose escalation trial assessing 3 dose cohorts using a 3+3 design to evaluate safety and tolerability of Allocetra-OTS in adult patients with moderate COVID-19. The sample size for this trial is anticipated to range from 9 to 18 patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Covid19
- What is being tested?
- Allocetra-OTS
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Dec 2021to Dec 2022
- Phase
- Phase 1
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female > 18 and < 80 years of age.
- Laboratory confirmation of SARS-CoV-2 infection by RT-PCR from any diagnostic sampling source.
- Patient hospitalized due to COVID-19 in the last 24 hours.
- Hospitalized patients meeting the criteria for moderate COVID-19, as set forth by the May 2020 FDA Guidance for Industry: COVID-19: Developing Drugs and Biological Products for Treatment or Prevention, Patients with symptoms of moderate illness with COVID-19, which could include any symptom of mild illness (such as fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea) or shortness of breath with exertion with at least one of the following clinical signs:
- Respiratory rate: ≥ 20 breaths/minute;
- SpO2: > 93% on room air at sea level;
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- Heart rate: ≥ 90 beats/minute;
- 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 enrolment .
Who cannot join
- Any signs indicative of Severe or Critical Illness Severity requiring hospitalization as defined below:
- Severe COVID-19: Shortness of breath in rest, or respiratory distress, or respiratory rate (RR≥30 per minute , or heart rate (HR) ≥125 bpm, or SpO2≤93% on room air at sea level or PaO2/FiO2<300
- Critical COVID-19- at least one of the following:
- Respiratory failure required at least one of the following: mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, ECMO.
- Shock
- Multi-organ dysfunction/failure.
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- Women who are pregnant or breast feeding.
- Weight <50 kg or >110 kg.
- Stage 4 and 5 severe chronic kidney disease or requiring dialysis with eGFR < 30 ml/min.
- Patients with active malignant tumor.
- Patients who are participating in other concurrent investigational clinical trials or have been treated with any experimental agents within 30 days prior to enrollment.
- Known active chronic viral infections including, but not limited to, active HBV, HCV, or HIV/AIDS or other chronic infections.
- Based on medical history and concomitant therapies that would suggest infection, have suspected clinical diagnosis of current active TB or, if known, latent TB treated for less than 4 weeks with appropriate anti-TB therapy per institutional guidelines; Based on medical history and concomitant therapies that would suggest infection, suspected serious, active bacterial, fungal, viral (including, but not limited to, active HBV, HCV, or HIV/AIDS).
- Known immunocompromised state or immunosuppressing medications taken for indications other than SARS-CoV-2 (i.e., agents including chronic corticosteroids > 10 mg/day, azathioprine, cyclosporine, cyclophosphamide).
- Known New York Heart Association (NYHA) class III and IV heart failure or unstable angina, ventricular arrhythmias, active ischemic heart disease , or myocardial infarction within six months prior to diagnosis of COVID-19.
- 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.
- Patients with Glasgow Coma Scale (GCS) <13 with verbal score <5.
- Estimated GFR < 25 ml/min.
- Hemoglobin < 8 gr%.
- Patients with history of chronic liver disease, evidence of acute cholangitis or cholecystitis. Patients with at least one of the following:
- ALT or AST > 5X ULN (upper limit of normal range)
- Bilirubin > 3 X ULN
- Combination of ALT/AST > 3 X ULN and elevated direct bilirubin>ULN
- Known history of transfusion reactions, hemolytic anemia, or allergic reaction.
- Organ allograft or previous history of stem cell transplantation.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Multi-Center , Sequential Dose Escalation Study, Evaluating Safety and Tolerability of Allocetra-OTS in Patients With COVID-19
Phase 1b, multi-center, open label, sequential dose escalation trial assessing 3 dose cohorts using a 3+3 design to evaluate safety and tolerability of Allocetra-OTS in adult patients with moderate COVID-19. The sample size for this trial is anticipated to range from 9 to 18 patients.
Read the detailed description
Potential patients, who will be identified as suffering from moderate COVID-19 (as set forth in the FDA guidance for industry dated May 2020) will be recruited.
After the patient has signed the Informed Consent Form (ICF), and after confirmation that the patient meets all eligibility criteria, the patient will be enrolled to the relevant dose group according to the following sequential design:
Single Intravenous (IV) dose of Allocetra-OTS with 5x10^9 cells, Single Intravenous (IV) dose of Allocetra-OTS with 10x10^9 cells, Two IV doses of Allocetra-OTS with10x10^9 cells each dose (separated by 72 hours).
Each dose cohort will consist of 3 and up to 6 patients. In each dose cohort, starting with dose cohort 1, a single patient will be enrolled and dosed. If no dose limiting toxicity (DLT) is observed after at least 1 week and following review of relevant safety data of the first patient in that cohort by the DMC, 2 additional patients will be enrolled.
If no DLT is seen in the initial 3 dosed patients within a certain cohort and following DMC review, the first patient in the next dose cohort can be enrolled, repeating the same sequence of enrollment as described above.
If 1 DLT is seen in the initial 3 dosed patients within a certain cohort, the cohort will be expanded to a total of 6 patients. If >2/6 patients experience a DLT, the MTD will be reached. If no more than 1 patient out of 6 experiences a DLT, the next sequence of enrollment will be continued.
DMC will review and assess safety data at the predefined timepoints to recommend on cohort expansion or cohort escalation.
Investigational Product (IP) administration will occur on Day 1 within 12±4 hours from the time of eligibility.
Following IP administration (Day 1), patients will be followed for safety and efficacy assessments through 6 months.
- Conditions
- Covid19
- Being tested
- Allocetra-OTS
- 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
Cell-based therapy comprised of allogeneic non-HLA matched peripheral blood mononuclear cells induced to an early apoptotic state.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Active comparator | Single Intravenous (IV) dose of Allocetra-OTS with 5x10^9 cells Receives: Drug: Allocetra-OTS |
| Cohort 2 | Active comparator | Single Intravenous (IV) dose of Allocetra-OTS with 10x10^9 cells Receives: Drug: Allocetra-OTS |
| Cohort 3 | Active comparator | Two IV doses of Allocetra-OTS with 10x10^9 cells in each dose Receives: Drug: Allocetra-OTS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Adverse Events
Number and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Measured: 28 days
Maximum Tolerated Dose (MTD)
The highest dose of Allocetra-OTS that did not cause a Dose-Limiting Toxicity (DLT) in 2/6 cohort patientsor maximally administered dose if no DLT is seen.
Measured: 28 days
Secondary outcomes (4)
Efficacy - PaO2 or SO2/FiO2 Ratio
Change in PaO2 or SO2/FiO2 Ratio
Measured: 28 days
Efficacy - mortality
All-cause mortality
Measured: 28 days
Efficacy - organ function / support measurements
Oxygen free days, vasopressors free days, cumulative days in ICU or IMU
Measured: 28 days
Efficacy - NEWS2 Score
Change from baseline in National Early Warning Score 2 (NEWS2)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study startDec 2021 (estimated)
- Primary completionSep 2022 (estimated)
- Study completionDec 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- sequential dose escalation using a 3+3 design
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Enlivex Therapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oren Hershkovitz, PhD, Study director, Enlivex Therapeutics R&D
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04659304
- Sponsor's protocol ID
- ENX-CL-03-001
- Status last verified
- Aug 2021
- First submitted
- 7 Dec 2020
- Last updated
- 18 Aug 2021
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center , Sequential Dose Escalation Study, Evaluating Safety and Tolerability of Allocetra-OTS in Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04659304
- Acronym / sponsor ID
- ENX-CL-03-001
- Conditions
- Covid19
- Keywords
- Cell therapy, Allocetra-OTS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Enlivex Therapeutics Ltd.Industry (pharma, biotech, devices)
- Study start
- Dec 2021 (estimated)
- Primary completion
- Sep 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 9 Dec 2020 (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.
Phase 1b, multi-center, open label, sequential dose escalation trial assessing 3 dose cohorts using a 3+3 design to evaluate safety and tolerability of Allocetra-OTS in adult patients with moderate COVID-19. The sample size for this trial is anticipated to range from 9 to 18 patients.
Detailed description
Potential patients, who will be identified as suffering from moderate COVID-19 (as set forth in the FDA guidance for industry dated May 2020) will be recruited.
After the patient has signed the Informed Consent Form (ICF), and after confirmation that the patient meets all eligibility criteria, the patient will be enrolled to the relevant dose group according to the following sequential design:
Single Intravenous (IV) dose of Allocetra-OTS with 5x10^9 cells, Single Intravenous (IV) dose of Allocetra-OTS with 10x10^9 cells, Two IV doses of Allocetra-OTS with10x10^9 cells each dose (separated by 72 hours).
Each dose cohort will consist of 3 and up to 6 patients. In each dose cohort, starting with dose cohort 1, a single patient will be enrolled and dosed. If no dose limiting toxicity (DLT) is observed after at least 1 week and following review of relevant safety data of the first patient in that cohort by the DMC, 2 additional patients will be enrolled.
If no DLT is seen in the initial 3 dosed patients within a certain cohort and following DMC review, the first patient in the next dose cohort can be enrolled, repeating the same sequence of enrollment as described above.
If 1 DLT is seen in the initial 3 dosed patients within a certain cohort, the cohort will be expanded to a total of 6 patients. If >2/6 patients experience a DLT, the MTD will be reached. If no more than 1 patient out of 6 experiences a DLT, the next sequence of enrollment will be continued.
DMC will review and assess safety data at the predefined timepoints to recommend on cohort expansion or cohort escalation.
Investigational Product (IP) administration will occur on Day 1 within 12±4 hours from the time of eligibility.
Following IP administration (Day 1), patients will be followed for safety and efficacy assessments through 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- sequential dose escalation using a 3+3 design
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Active comparator | Drug: Allocetra-OTSSingle Intravenous (IV) dose of Allocetra-OTS with 5x10^9 cells |
| Cohort 2 | Active comparator | Drug: Allocetra-OTSSingle Intravenous (IV) dose of Allocetra-OTS with 10x10^9 cells |
| Cohort 3 | Active comparator | Drug: Allocetra-OTSTwo IV doses of Allocetra-OTS with 10x10^9 cells in each dose |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female > 18 and < 80 years of age.
- Laboratory confirmation of SARS-CoV-2 infection by RT-PCR from any diagnostic sampling source.
- Patient hospitalized due to COVID-19 in the last 24 hours.
- Hospitalized patients meeting the criteria for moderate COVID-19, as set forth by the May 2020 FDA Guidance for Industry: COVID-19: Developing Drugs and Biological Products for Treatment or Prevention, Patients with symptoms of moderate illness with COVID-19, which could include any symptom of mild illness (such as fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea) or shortness of breath with exertion with at least one of the following clinical signs:
- Signed written informed consent by the patient.
Key exclusion criteria (25 listed)
- Any signs indicative of Severe or Critical Illness Severity requiring hospitalization as defined below:
- Severe COVID-19: Shortness of breath in rest, or respiratory distress, or respiratory rate (RR≥30 per minute , or heart rate (HR) ≥125 bpm, or SpO2≤93% on room air at sea level or PaO2/FiO2<300
- Women who are pregnant or breast feeding.
- Weight <50 kg or >110 kg.
- Stage 4 and 5 severe chronic kidney disease or requiring dialysis with eGFR < 30 ml/min.
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-OTSCell-based therapy comprised of allogeneic non-HLA matched peripheral blood mononuclear cells induced to an early apoptotic state. | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Safety - Adverse Events
Time frame: 28 days
Number and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Maximum Tolerated Dose (MTD)
Time frame: 28 days
The highest dose of Allocetra-OTS that did not cause a Dose-Limiting Toxicity (DLT) in 2/6 cohort patientsor maximally administered dose if no DLT is seen.
4 secondary outcomes
Efficacy - PaO2 or SO2/FiO2 Ratio
Time frame: 28 days
Efficacy - mortality
Time frame: 28 days
Efficacy - organ function / support measurements
Time frame: 28 days
Efficacy - NEWS2 Score
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
- 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.
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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.
Oren Hershkovitz, PhD study director
Enlivex Therapeutics R&D
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allocetra-OTS in people with Covid19, run by Enlivex Therapeutics Ltd..
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 9 inclusion and 25 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 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Odelia Ben Shitrit, MBA (972-548887609, odelia@enlivexpharm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety - Adverse Events (time frame: 28 days). The study lists 2 primary outcomes in all. 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 18 Aug 2021.