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

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Enlivex Therapeutics Ltd.

Criteria

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.