Early Treatment of Cytokine Storm Syndrome in Covid-19

NCT04362111 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: Chatham-Cytokine Covid-19
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal addresses the problem of preventing the very high mortality and morbidity associated with the development of Cytokine Storm Syndrome (CSS) associated respiratory failure in Covid-19 infection.

Conditions

Cytokine Storm; COVID-19

Outcome Measures

Primary Outcomes (1)

• Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation.

  Percentage of subjects discharged from hospital alive and who did not require intubation and mechanical ventilation

  Variable up to Day 28

Secondary Outcomes (6)

• Percentage of Subjects With 25% Change (Decrease) in Cytokine Storm Markers at 48-72 Hours After Dosing With Study Agent

  48 hours after taking initial dose of anakinra/placebo

• Percentage of Subjects Without Increase in Oxygen Requirement and no Increase in Oxygen Delivery/Respiratory Support Measures After 48 Hours.

  Day 2 (48 hours)-Day 10 (240 hours)

• Patients Requiring Minimal Oxygen Support at Day 10

  0-10 days

• Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome

  Day 10

• Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection

  Day 0-28

Study Arms (2)

Anakinra Group

EXPERIMENTAL

The active treatment group will receive anakinra 100 mg subcutaneously every 6 hours for period of 10 days. For subjects meeting complete response criteria at 5 days, dosing will be decreased to 100 mg twice daily for the remaining 5 days.

Drug: Anakinra

Control Group

PLACEBO COMPARATOR

The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete response criteria at 5 days, dosing will be decreased to twice daily for the remaining 5 days.

Drug: Normal saline

Interventions

Anakinra DRUG

The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days

Also known as: recombinant human IL-ra (rhIL-1ra)

Anakinra Group

Normal saline DRUG

The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days

Also known as: NS

Control Group

Eligibility Criteria

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

You may qualify if:

• years old or older
• Molecular (pcRNA) diagnosis of SARS-CoV-2 infection
• Chest imaging studies consistent with Covid-19 pneumonia
• Hyperferritinemia (\>700 ng/ml)
• History of fever \>38 degrees C
• Any three of the following:
• Elevated d-dimer (\> 500 ng/ml)
• thrombocytopenia (\< 130,000/mm3)
• leucopenia (WBC \<3500/mm3) or lymphopenia (\<1000/mm3)
• elevated AST or ALT (\> 2X ULN)
• elevated LDH (\> 2X ULN)
• CRP \> 100 mg/L

You may not qualify if:

• Participation in other investigational treatment protocols for Covid-19 infection
• Culture confirmed active bacterial infection requiring antibiotic therapy
• On mechanical ventilation
• Previous known hypersensitivity reaction to anakinra
• Previous known hypersensitivity reaction to E Coli derived proteins
• Pregnant or breast-feeding females

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Cytokine Release Syndrome; COVID-19

Interventions

Interleukin 1 Receptor Antagonist Protein; Saline Solution

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; 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)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

1. All subjects received daily dexamethasone to the standard of care management of Covid-19 pneumonia requiring hospitalization. 2. Some of the enrolled subjects with rapid improvement were discharged prior to 10 days with instructions on anakinra self-administration at home; adherence with unsupervised dosing of study agent could not be readily assessed, nor could reported oxygen saturations be confirmed in these participants.

Results Point of Contact

• Title: Walter Winn Chatham MD
• Organization: University of Alabama at Birmingham

wchatham@uabmc.edu

205-612-7402

Study Officials

• Walter W Chatham, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Investigator, care provider, and participant blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Two parallel treatment arms

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: August 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: June 1, 2023
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: During study enrollment
• Access Criteria: wchatham@uabmc.edu

Locations

US (1)