Hyperimmune anti-COVID-19 Intravenous Immunoglobulin vs Standard care/Placebo (RCT)

Mild outpatients

FOREST PLOTS -2022-12-15

Studies description

Trial NCT04847141
Publication NCT04847141, Unpublished (2022) (results posted on registry)

Funding: Not reported/unclear
Conflict of interest: *

Methods
RCT
Blinding: quadruple blinding
Location : Multicenter / Spain
Follow-up duration (days): 60
Inclusion criteria
  • Ambulatory male or female outpatients ≥ 18 years of age who have laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by qualitative PCR (reverse transcriptase (RT)-PCR), or other commercial or public health assay approved by regulatory authorities as a diagnostic test for COVID-19 (inclusive of SARS-CoV-2 antigen testing or other approved rapid testing platforms) in any specimen ≤ 5 days prior to randomized treatment.
  • Asymptomatic with no constitutional COVID-19 illness (evident symptoms), specifically no fever, cough, shortness of breath, fatigue, anorexia, vomiting/diarrhea, headache that is unrelated to pre-existing conditions (example, migraine), sore throat that is unrelated to other pre-existing medical conditions (example, allergies, gastroesophageal reflux disease), myalgias, olfactory disorders unrelated with previous medical condition, or evidence of pneumonia at Screening.
  • Pulse oximetry peripheral oxygen saturation (SpO2) (oxygen saturation) on room air > 94% (i.e., 95% to 100%) at Screening.
  • National Early Warning Score (NEWS) ≤ 2 points at Screening.
  • Participant provides informed consent (ICF) prior to initiation of any study procedures.
Exclusion criteria
  • Participants who are admitted to hospital or for whom hospital admission is being planned at the time of Screening.
  • Participants requiring any form of oxygen supplementation at Screening.
  • Concurrent or planned treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 including remdesivir.
  • Prior, concurrent or planned treatment with monoclonal antibodies (mAbs) against SARS-CoV-2.
  • Have participated in a previous SARS-CoV-2 vaccine study OR outside of a study have received any SARS-CoV-2 vaccine of any kind.
  • Have a history of convalescent COVID-19 plasma treatment at Screening.
  • Fever (temperature ≥38.0° C [≥100.4° F]), measured orally, requirement for antipyretics to reduce temperature (administered for fever), and/or respiratory symptoms (cough, dyspnea) at Screening.
  • Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the participant at undue medical risk for study treatment.
  • The participant has had a known (documented) history of serious anaphylactic reaction to blood, any blood-derived plasma product or commercial immunoglobulin, or has known selective immunoglobulin A (IgA) deficiency with anti-IgA antibodies.
  • Decompensated congestive heart failure or renal failure with fluid overload. This includes currently uncontrolled congestive heart failure New York Heart Association Class III or IV stage heart failure.
  • Participants for whom there is limitation of therapeutic effort such as "Do not resuscitate" status.
  • Currently participating in another interventional clinical trial with investigational medical product or device.
  • Participants with known (documented) thrombotic complications to polyclonal intravenous immune globulin (IVIG) therapy in the past.
  • Participant has medical condition (other than COVID-19) that is projected to limit lifespan to ≤ 1 year.
  • Participant has history of drug or alcohol abuse within the past 12 months.
  • Participant is unwilling to commit to follow-up visits.
  • Women who are pregnant or breastfeeding, or if of childbearing potential, unwilling to practice a highly effective method of contraception (oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom, or occlusive cap with spermicidal foam/gel/cream/suppository, male sterilization, or true abstinence) throughout the study.
Interventions
Treatment
C-IVIG 2g
2g subcutaneously single dose

C-IVIG 1g
1g subcutaneously single dose

C-IVIG
1g subcutaneously single dose
Control
Placebo

Participants
Randomized
NR

Analyzed
766 participants Placebo=156
C-IVIG 2g=153
C-IVIG 1g=152
C-IVIG=305
Characteristics of participants
N= 766
Mean age : NR
350 males
Severity : Mild: n= 0/ Asymptomatic: n=613
Primary outcome
In the register
Percentage of Asymptomatic Participants Who Remained Asymptomatic, i.e., Who Did Not Develop Symptomatic COVID-19 Through Day 14 [ Time Frame: Up to Day 14 ]
In the report
NR
Documents
avalaible

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Not reported
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start. The trial (n = 465) did not achieve its target sample size (n = 801). The study was terminated for futility..