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

Sponsor

Instituto Grifols, S.A. (Industry)

Overall Status

Completed

CT.gov ID

NCT04432324

Collaborator

(none)

100

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: Intravenous Immune Globulin Drug: Standard Medical Treatment	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 2, 2020

Actual Primary Completion Date :

Mar 3, 2021

Actual Study Completion Date :

Mar 3, 2021

Arms and Interventions

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.	Biological: Intravenous Immune Globulin IVIG Intravenous infusion Other Names: Flebogamma DIF Drug: Standard Medical Treatment SMT
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

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.

Biological: Intravenous Immune Globulin

IVIG Intravenous infusion

Other Names:

Flebogamma DIF

Drug: Standard Medical Treatment

SMT

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

Outcome Measures

Primary Outcome Measures

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

Change from Baseline in National Early Warning Score (NEWS) [Day 1 through Day 29]
Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours [Day 1 through Day 29]
Time to Hospital Discharge [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]
Mean Change from Baseline in Ordinal Scale [Day 1 through Day 29]
Absolute Value Change from Baseline in Ordinal Scale [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]
Time to Sustained Normalization of Temperature [Day 1 through 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Hospitalized male or female subject ≥ 18 years of age at time of Screening who is being treated for COVID-19.
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.
COVID-19 illness (symptoms) of any duration with radiographic infiltrates by imaging (Chest X-Ray, Computed tomography (CT) scan, etc.).
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])
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).
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:

Subject requires invasive mechanical ventilation or ICU admission.
Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator may place the subject at undue medical risk.
The subject has had a known (documented) serious anaphylactic reaction to blood, any blood-derived or plasma product or commercial immunoglobulin.
Subject has known (documented) hereditary fructose intolerance (HFI).
A medical condition in which the infusion of additional fluid is contraindicated.
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.
Subject with known (documented) thrombotic complications to polyclonal IVIG therapy in the past.
Subject with current or prior (within the past 1 month) myocardial infarction, stroke, deep vein thrombosis, or thromboembolic event.
Subject with limitations of therapeutic effort (eg, 'do not resuscitate' status).
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.
Subject participating in another interventional clinical trial with investigational medical product or device.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Infanta Sofía	San Sebastián De Los Reyes	Madrid	Spain	28702
2	Hospital Germans Trias i Pujol	Badalona		Spain	08916
3	Hospital Del Mar	Barcelona		Spain	08003
4	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
5	Hospital Universitari de Bellvitge	Barcelona		Spain	08907
6	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	CP 08041
7	Hospital Universitario de Getafe	Getafe		Spain	28905
8	Hospital Arnau de Vilanova	Lleida		Spain	25198
9	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
10	Hospital Clinico San Carlos	Madrid		Spain	28040