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Study Evaluating Safety and Tolerability of Allocetra-OTS in Patients With COVID-19

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ClinicalTrials.gov Identifier: NCT04659304
Recruitment Status : Not yet recruiting
First Posted : December 9, 2020
Last Update Posted : April 15, 2021
Sponsor:
Information provided by (Responsible Party):
Enlivex Therapeutics Ltd.

Tracking Information
First Submitted Date  ICMJE December 7, 2020
First Posted Date  ICMJE December 9, 2020
Last Update Posted Date April 15, 2021
Estimated Study Start Date  ICMJE June 2021
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2021)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
Safety - Adverse Events [ Time Frame: 28 days ]
Number and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2021)
  • Efficacy - PaO2 or SO2/FiO2 Ratio [ Time Frame: 28 days ]
    Change in PaO2 or SO2/FiO2 Ratio
  • Efficacy - mortality [ Time Frame: 28 days ]
    All-cause mortality
  • Efficacy - organ function / support measurements [ Time Frame: 28 days ]
    Oxygen free days, vasopressors free days, cumulative days in ICU or IMU
  • Efficacy - NEWS2 Score [ Time Frame: 28 days ]
    Change from baseline in National Early Warning Score 2 (NEWS2)
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
  • Efficacy - PaO2 or SO2/FiO2 Ratio [ Time Frame: 28 days ]
    Change in PaO2 or SO2/FiO2 Ratio
  • Efficacy - SOFA score [ Time Frame: 7 days ]
    Change from baseline in Sequential Organ Failure Assessment (SOFA) score
  • Efficacy - mortality [ Time Frame: 28 days ]
    All-cause mortality
  • Efficacy - organ function / support measurements [ Time Frame: 28 days ]
    Improvement from baseline in oxygen free days, vasopressors free days, cumulative days in ICU or IMU
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Safety and Tolerability of Allocetra-OTS in Patients With COVID-19
Official Title  ICMJE A Multi-Center , Sequential Dose Escalation Study, Evaluating Safety and Tolerability of Allocetra-OTS in Patients With COVID-19
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
sequential dose escalation using a 3+3 design
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Covid19
Intervention  ICMJE Drug: Allocetra-OTS
Cell-based therapy comprised of allogeneic non-HLA matched peripheral blood mononuclear cells induced to an early apoptotic state.
Study Arms  ICMJE
  • Active Comparator: Cohort 1
    Single Intravenous (IV) dose of Allocetra-OTS with 5x10^9 cells
    Intervention: Drug: Allocetra-OTS
  • Active Comparator: Cohort 2
    Single Intravenous (IV) dose of Allocetra-OTS with 10x10^9 cells
    Intervention: Drug: Allocetra-OTS
  • Active Comparator: Cohort 3
    Two IV doses of Allocetra-OTS with 10x10^9 cells in each dose
    Intervention: Drug: Allocetra-OTS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2021)
18
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2020)
50
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male and female > 18 and < 80 years of age.
  2. Laboratory confirmation of SARS-CoV-2 infection by RT-PCR from any diagnostic sampling source.
  3. Patient hospitalized due to COVID-19 in the last 24 hours.
  4. 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:

    1. Respiratory rate: ≥ 20 breaths/minute;
    2. SpO2: > 93% on room air at sea level;
    3. Heart rate: ≥ 90 beats/minute;
  5. Signed written informed consent by the patient.
  6. Women and men who are of childbearing potential, willing to use acceptable contraceptive measures during 4 weeks from enrolment .

Exclusion Criteria:

  1. 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.
  2. Women who are pregnant or breast feeding.
  3. Weight <50 kg or >110 kg.
  4. Stage 4 and 5 severe chronic kidney disease or requiring dialysis with eGFR < 30 ml/min.
  5. Patients with active malignant tumor.
  6. Patients who are participating in other concurrent investigational clinical trials or have been treated with any experimental agents within 30 days prior to enrollment.
  7. 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).

  8. 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).
  9. 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.
  10. 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.
  11. Patients with Glasgow Coma Scale (GCS) <13 with verbal score <5.
  12. Estimated GFR < 25 ml/min.
  13. Hemoglobin < 8 gr%.
  14. 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
  15. Known history of transfusion reactions, hemolytic anemia, or allergic reaction.
  16. Organ allograft or previous history of stem cell transplantation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Odelia Ben Shitrit, MBA 972-548887609 odelia@enlivexpharm.com
Contact: Lior Binder 972-548054899 lior@enlivexpharm.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04659304
Other Study ID Numbers  ICMJE ENX-CL-03-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Patient data will not contain any information which would make the patient identifiable. Data will be processes and shared using patient study number only.
Responsible Party Enlivex Therapeutics Ltd.
Study Sponsor  ICMJE Enlivex Therapeutics Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Oren Hershkovitz, PhD Enlivex Therapeutics R&D
PRS Account Enlivex Therapeutics Ltd.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP