Study to Evaluate the Safety and Efficacy of High Dose IVIG in Hospitalized Participants With Coronavirus Disease (COVID-19)

A Multicenter, Randomized, Open-label Parallel Group Pilot Study to Evaluate Safety and Efficacy of High Dose Intravenous Immune Globulin (IVIG) Plus Standard Medical Treatment (SMT) Versus SMT Alone in Hospitalized Subjects With COVID-19

The purpose of the study is to determine if high dose Intravenous IVIG plus SMT can reduce the proportion of participants dying or requiring intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical ventilation on Day 29 versus SMT alone in hospitalized participants with COVID-19.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Standard Medical Treatment; Biological: Intravenous Immune Globulin

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain, CP 08041
    • Hospital De La Santa Creu I Sant Pau
  • Getafe, Spain, 28905
    • Hospital Universitario de Getafe
  • Lleida, Spain, 25198
    • Hospital Arnau de Vilanova
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid
    • San Sebastián De Los Reyes, Madrid, Spain, 28702
      • Hospital Universitario Infanta Sofía

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hospitalized male or female subject ≥ 18 years of age at time of Screening who is being treated for COVID-19.
2. Has laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by qualitative Polymerase Chain Reaction (PCR) (reverse transcriptase [RT]-PCR), or other commercial or public health assay (of any type) in any specimen during the current hospital admission prior to randomization.
3. COVID-19 illness (symptoms) of any duration with radiographic infiltrates by imaging (Chest X-Ray, Computed tomography (CT) scan, etc.).
4. PaO2/FIO2 ratio > 300 to ≤ 450 mmHg (i.e., arterial oxygen in mmHg divided by fraction inspired oxygen concentration [e.g., 0.21 for room air])
5. Any one of the following related to COVID-19: i. Ferritin > 400 nanogram per milliliter (ng/mL), ii. Lactate dehydrogenase (LDH) > 300 units per liter U/L, iii. D-Dimers > reference range, or iv. C-reactive protein (CRP) > 40 milligram per liter (mg/L).
6. Subject (or a legal representative or a nearest relative or a relative by marriage, as appropriate) provides oral informed consent prior to initiation of any study procedures.

Exclusion criteria:

1. Subject requires invasive mechanical ventilation or ICU admission.
2. Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator may place the subject at undue medical risk.
3. The subject has had a known (documented) serious anaphylactic reaction to blood, any blood-derived or plasma product or commercial immunoglobulin.
4. Subject has known (documented) hereditary fructose intolerance (HFI).
5. A medical condition in which the infusion of additional fluid is contraindicated.
6. Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered by the Principal Investigator not able to be reversed.
7. Subject with known (documented) thrombotic complications to polyclonal IVIG therapy in the past.
8. Subject with current or prior (within the past 1 month) myocardial infarction, stroke, deep vein thrombosis, or thromboembolic event.
9. Subject with limitations of therapeutic effort (eg, 'do not resuscitate' status).
10. Female subject who are pregnant or of child-bearing potential with a positive test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at Screening/Baseline.
11. Subject participating in another interventional clinical trial with investigational medical product or device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Immune Globulin + Standard Medical Treatment; Participants will receive the first intravenous (IV) infusion of IVIG on Day 1 up to a net dose of 2 gram per kilogram (g/kg), based upon participant's (body weight) administered in divided doses as infusions of 500 milligram per kilogram (mg/kg), based upon participant's body weight, over 4 days or 400 mg/kg, based upon participant's body weight, over 5 days. Participants will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.	Drug: Standard Medical Treatment; SMT; Biological: Intravenous Immune Globulin; IVIG Intravenous infusion; Other Names: Flebogamma DIF
Active Comparator: Standard Medical Treatment; Participants will receive all standard of care interventions required throughout the participant's hospitalization, from Day 1 to Day 29	Drug: Standard Medical Treatment; SMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Dying or Requiring ICU Admission	Up to Day 29
Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation	Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in National Early Warning Score (NEWS)	Day 1 through Day 29
Time to Hospital Discharge	Day 1 through Day 29
Absolute Value Change from Baseline in Ordinal Scale	Day 1 through Day 29
Mean Change from Baseline in Ordinal Scale	Day 1 through Day 29
Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours	Day 1 through Day 29
Duration of ICU Stay	Up to Day 29
Duration of Any Oxygen Use	Day 1 through Day 29
Duration of Mechanical Ventilation	Up to Day 29
Time to Sustained Normalization of Temperature	Day 1 through Day 29
Length of Time to Clinical Progression	Up to Day 29
Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale	Day 15 and Day 29
Percentage of Participants with Normalization of Fever	Day 1 through Day 29
Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)	Day 29

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Actual): March 3, 2021
• Study Completion (Actual): March 3, 2021

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Coronavirus Disease
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: GC2004; 2020-001696-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes