Etoposide in Patients With COVID-19 Infection

NCT04356690 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: H-40102
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label phase II study designed to evaluate the safety and efficacy of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the investigator and treating physician believe the patient had clinical benefit from etoposide therapy but subsequently has evidence of recurrent clinical deterioration. Subjects randomized to control will receive standard of care treatment. No placebo will be used.

Conditions

COVID-19

Keywords

Etoposide; hemophagocytic lymphohistiocytosis (HLH); cytokine storm

Outcome Measures

Primary Outcomes (1)

• Improvement in Pulmonary Status by Two Categories on an 8 Point Ordinal Scale of Respiratory Function

  8-Point Ordinal Scale of Respiratory Function: 8 -Death; 7 -Ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT), or need for vasopressors (dopamine ≥5 μg/kg/min OR epinephrine ≥0.1 μg/kg/min OR norepinephrine ≥0.1 μg/kg/min) 6 -Intubation and mechanical ventilation 5 -Non-invasive mechanical ventilation (NIV) or high-flow oxygen 4 -Hospitalized, requiring oxygen by mask or nasal prongs 3 -Hospitalization without oxygen supplementation 2-Discharged from hospital either to home with supplemental oxygen OR to inpatient rehabilitation/skilled nursing facility(+/-supplemental oxygen); 1 -Discharged to home without supplemental oxygen

  baseline, through hospital discharge or death

Secondary Outcomes (8)

• Overall Survival

  30 Days

• Length of Hospitalization

  From date of enrollment until date of discharge

• Duration of Ventilation After Treatment

  From date of enrollment until the date of extubation

• Change in Blood Ferritin Levels

  baseline, to day 30 (or discharge or death)

• Change in C-reactive Protein (CRP) Levels

  baseline, to day 30 (or discharge or death)

Study Arms (2)

Cohort 1 - Etoposide

EXPERIMENTAL

Participants that are on ventilation Etoposide 150 mg/m2 daily days 1 and 4

Drug: Etoposide

Cohort 1 - Control

NO INTERVENTION

Standard of care therapy in participants that are on ventilation

Interventions

Etoposide DRUG

Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4.

Also known as: Etopophos

Cohort 1 - Etoposide

Eligibility Criteria

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

You may qualify if:

• Confirmed COVID-19 infection
• Evidence of cytokine storm defined as:
• Peak ferritin \> 10,000 ng/mL OR
• Peak ferritin \> 500 ng/mL and one or more of the following at any time during hospital admission: Lactate dehydrogenase \> 500 U/L, d-dimer \>1000 ng/mL, C-reactive protein \> 100 mg/L, or white blood count\> 15 k/microlitre
• Cohort 1: Intubated status as a result of COVID infection-associated respiratory illness.

You may not qualify if:

• Pregnancy or breastfeeding
• History of severe hypersensitivity to etoposide products
• Absolute neutrophil count (ANC) \< 1000 cells/mm3
• Platelet count \<50,000/mm3
• Bilirubin \> 3.0 mg/dL
• Aspartate OR alanine aminotransferase \> 5.0 x upper limit of normal
• Creatinine Clearance \< 15 mL/min (calculated by Cockcroft Fault formula)
• Requiring continuous renal replacement therapy
• Requiring \>1 vasopressor
• Requiring extracorporeal membrane oxygenation (ECMO)
• Other active, life-threatening infections
• Anti-cytokine treatment (including anakinra or Interleukin 6 antibodies eg tocilizumab, sarilumab) administration within three half-lives of the medication used
• Hydroxychloroquine, colchicine, azithromycin, doxycycline-if administered for COVID infection-must be discontinued for at least 24 hours prior to randomization.
• Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with subject participation, or is not in the best interest of the patient to participate, in the opinion of the investigator.
• Inability to consent and no legally authorized representative

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

COVID-19; Lymphohistiocytosis, Hemophagocytic; Cytokine Release Syndrome

Interventions

Etoposide; etoposide phosphate

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; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

The study was halted prematurely due to slow accrual, change in COVID prevalence, and the availability of an effective vaccine.

Results Point of Contact

• Title: John Mark Sloan, MD
• Organization: Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center

mark.sloan@bmc.org

617-638-7002

Study Officials

• John Mark Sloan, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 22, 2020
• Study Start: May 8, 2020
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: June 15, 2023
• Results First Posted: June 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)