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)

NCT04922957 | Terminated Phase 2 DMC

• 1 other identifier: ENX-CL-03-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 syndrome (ARDS). Patients will be followed for efficacy and safety for 6 months. The trial will include periodic and ad-hoc DSMB review during the study period.

Conditions

Covid19

Keywords

Cell therapy; Allocetra-OTS

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  28 days

• Mortality

  Mortality by Day 28 post study treatment administration. Deceased patients will be assigned the maximal score of 29.

  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.

  60 days

• All-cause mortality during the period of 28 days and 60 days.

  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.

  60 days

• Cumulative number of vasopressor-free days during the period of 28 days and 60 days.

  60 days

• Cumulative number of days in the hospital during the period of 28 days and 60 days.

  60 days

Other Outcomes (2)

• Safety - Number and severity of adverse events (AEs) and serious adverse events (SAEs) throughout 60-day follow-up period

  60 days

• Safety - Number and severity of AEs and SAEs throughout 180-day follow-up period

  180 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Ringer's lactate solution

Other: Placebo

ALLOCETRA-OTS

EXPERIMENTAL

Single IV dose of Allocetra-OTS containing 10x10\^9 cells

Drug: ALLOCETRA-OTS

Interventions

ALLOCETRA-OTS DRUG

The product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.

Also known as: Cell based therapy, Apoptotic cells

ALLOCETRA-OTS

Placebo OTHER

Ringer's lactate solution

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• \< PaO2/FiO2 ≤300; based on the Berlin Definition of ARDS
• \< 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Enlivex Therapeutics Ltd.: lead

Study Sites (1)

Hadassah Ein Kerem Medical Center

Jerusalem, Israel

Location

MeSH Terms

Conditions

COVID-19

Interventions

Cell- and Tissue-Based Therapy

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Oren Hershkovitz, PhD

  Enlivex Therapeutics R&D

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be in a double blinding fashion. The IP will be delivered with a cover to maintain blinding.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 11, 2021
• Study Start: September 1, 2021
• Primary Completion: April 1, 2022
• Study Completion: March 11, 2024
• Last Updated: March 13, 2024

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)