Allocetra-OTS in COVID-19, Phase II

NCT04590053 | Unknown Phase 2

• 1 other identifier: DM004
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in up to 24 subjects with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited. After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below. Subjects will be hospitalized for COVID-19, and later as medically indicated. Following the investigational product (IP) administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Assessment of safety by determining the number of participants with any Adverse Events (AE) and Serious Adverse Events (SAE)

  Incidence rates and severity of any Adverse Events (AE) and Serious Adverse Events (SAE)

  28 days follow up

Secondary Outcomes (13)

• Preliminary Efficacy: Recovery from COVID-19 as determined by negative PCR or asymptomatic by the NIH classification for the severity of illness

  28 days follow up

• Mortality

  28 days follow up

• Preliminary Efficacy: To assess prevention of respiratory deterioration associated with COVID-19 by measuring the PaO2/FiO2 ratio

  On days, 3, 5, 7, 14, and 28 during 28 days follow up

• Hospitalization

  28 days follow up

• Life support

  28 days follow up

Study Arms (1)

COVID-19

EXPERIMENTAL

Up to 24 subjects, male or female \> 18 and \< 80-year-old diagnosed with respiratory dysfunction and COVID-19, as defined in the Eligibility Criteria, and treated with a single intravenous dose of Allocetra-OTS investigational product as detailed in the Interventions section.

Biological: Allocetra-OTS

Interventions

Allocetra-OTS BIOLOGICAL

Allocetra-OTS is a cell-based therapeutic composed of donor early apoptotic cells, comprising allogeneic mononuclear enriched cell suspension with at least 40% early apoptotic cells. The suspension is prepared with Ringer's lactate solution and administered IV. It is stored at 2-8°C until 20+25 minutes before infusion and at room temperature thereafter. Each dose contains 140x10E6 ± 20% cells/ kg of recipient body weight (at screening) in a total volume of 375 mL in a transfer pack that undergoes irradiation and is administered via an adjusted filter using a volumetric pump, at a starting rate of 48 mL/hour with a gradual increase every 15-25 minutes of 15 mL/hour to a maximal rate of 102 mL/hour. The study intervention should be completed within 72 hours of completing the manufacturing process. During product administration, no other IV fluids such as Ringer's lactate or normal saline will be given in parallel unless medically indicated due to volume depletion.

COVID-19

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Up to twenty-four subjects, male or female \> 18 and \< 80-year-old diagnosed with COVID-19, as defined below:
• Laboratory confirmation of SARS-COV2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source.
• Patients classified as severe or critical according to NIH severity classification.
• All patients will be treated by treating physician with S.C. Clexane, at a minimal dose of 40 mg a day
• Illness with at least one of the following:
• Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
• SpO2 ≤ 94% on room air, OR
• Requiring supplemental oxygen, with a P/F ratio of ≤350, ≥150
• Signed written informed consent by the patient.

You may not qualify if:

• Pregnancy, lactation, and childbearing potential woman who are not willing to use acceptable contraceptives measures for the entire study duration.
• Combined with other organ failures (need organ support not including respirator), including Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) \< 30)
• Patients with a malignant tumor, other serious systemic diseases and psychosis.
• Patients who are participating in other clinical trials or treated with any experimental agents that may contradict this trial (i.e, biologics)
• Co-Infection of HIV, tuberculosis.
• Known immunocompromised state or medications known to be immunosuppressive (see concomitant prohibited medications on the next page).
• Intubated patients (due to inability to sign an informed consent)
• Patients with P/F or S/F ratio of \<150 or a change in status of eligibility manifested by a rapid decline of P/F ratio between eligibility status and actual drug delivery.

Sponsors & Collaborators

• Hadassah Medical Organization: lead
• Barzilai Medical Center: collaborator
• Tel-Aviv Sourasky Medical Center: collaborator

Study Sites (3)

Barzilai Medical Center

Ashkelon, 7830604, Israel

NOT YET RECRUITING

Hadassah Medical Center

Jerusalem, 91120, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

NOT YET RECRUITING

Related Publications (1)

• van Heerden PV, Abutbul A, Naama A, Maayan S, Makram N, Nachshon A, Abu Jabal K, Hershkovitz O, Binder L, Shabat Y, Reicher B, Mevorach D. Apoptotic cells for treatment of acute respiratory distress syndrome associated with COVID-19. Front Immunol. 2023 Aug 2;14:1242551. doi: 10.3389/fimmu.2023.1242551. eCollection 2023.

  PMID: 37600829 DERIVED

MeSH Terms

Conditions

COVID-19

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

Study Officials

• Dror Mevorach, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

• Peter V van Heerden, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dror Mevorach, MD

CONTACT

972-2- 6777317; mevorachd@hadassah.org.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Head, Department of Internal Medicine B; Head, Rheumatology Research Center, Hadassah and the Hebrew University Medical School

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: October 19, 2020
• Study Start: October 20, 2020
• Primary Completion: February 1, 2021
• Study Completion: March 1, 2021
• Last Updated: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3)