Hyperimmune intravenous immunoglobulin does not improve outcomes for
adults hospitalized with COVID-19, study finds
NIH trial compared hIVIG plus remdesivir to remdesivir alone

Date:
January 28, 2022
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
A clinical trial has found that the combination of remdesivir
plus a highly concentrated solution of antibodies that neutralize
SARS-CoV-2, the virus that causes COVID-19, is not more effective
than remdesivir alone for treating adults hospitalized with the
disease. The trial also found that the safety of this experimental
treatment may vary depending on whether a person naturally generates
SARS-CoV-2-neutralizing antibodies before receiving it.



FULL STORY ==========================================================================
A clinical trial has found that the combination of remdesivir plus a
highly concentrated solution of antibodies that neutralize SARS-CoV-2,
the virus that causes COVID-19, is not more effective than remdesivir
alone for treating adults hospitalized with the disease. The trial also
found that the safety of this experimental treatment may vary depending on whether a person naturally generates SARS-CoV-2-neutralizing antibodies
before receiving it. The results of the multinational Phase 3 trial were published today in the journal The Lancet.


==========================================================================
The National Institute of Allergy and Infectious Diseases (NIAID), part
of the National Institutes of Health, sponsored and funded the trial,
called Inpatient Treatment with Anti-Coronavirus Immunoglobulin, or
ITAC. The trial was conducted by the NIAID-funded International Network
for Strategic Initiatives in Global HIV Trials (INSIGHT). Mark Polizzotto, M.D., Ph.D., head of the Clinical Hub for Interventional Research at
the College of Health & Medicine of The Australian National University
in Canberra, led the trial.

The antibody solution tested in the ITAC trial was anti-coronavirus
hyperimmune intravenous immunoglobulin, or hIVIG. The antibodies in anti-coronavirus hIVIG came from the liquid portion of blood, or plasma, donated by healthy people who had recovered from COVID-19. These
antibodies were highly purified and concentrated so that the
anti-coronavirus hIVIG consistently contained several times more
SARS-CoV-2 neutralizing antibodies than typically found in the plasma
of people who have recovered from COVID-19.

"In our quest to find safe and effective treatments for COVID-19, we
had hoped that adding anti-coronavirus hIVIG to a remdesivir regimen
would give the immune system a boost to help suppress the virus early in
the course of hospitalization," said NIAID Director Anthony S. Fauci,
M.D. "Unfortunately, the ITAC trial demonstrated that this strategy
did not improve the health of adults hospitalized with COVID-19 and
may be harmful for a certain subset of patients. Studies testing this
strategy in non-hospitalized adults earlier in the course of infection
are underway." Four companies collaborated to provide anti-coronavirus
hIVIG for the trial: Emergent BioSolutions of Gaithersburg, Maryland;
Grifols S.A. of Barcelona; CSL Behring of King of Prussia, Pennsylvania;
and Takeda of Tokyo.

Remdesivir is a broad-spectrum antiviral currently approved by the
U.S. Food and Drug Administration and recommended for treating certain
patients with COVID-19 based on data from several randomized clinical
trials, including the NIAID-sponsored Adaptive COVID-19 Treatment Trial (ACTT-1). FDA granted the approval to Gilead Sciences, Inc. of Foster
City, California.

The ITAC study team enrolled nearly 600 hospitalized adults aged 18
years or older who had COVID-19 symptoms for up to 12 days and did not
have life- threatening organ dysfunction or organ failure. Enrollment
took place at 63 sites in 11 countries in Africa, Asia, Europe, North
America and South America between October 2020 and February 2021. Study participants were assigned at random to receive infusions of either anti-coronavirus hIVIG and remdesivir or a placebo and remdesivir. Neither
the participants nor the study team, except for pharmacists who prepared
the infusions, knew who received which treatment regimen until the end
of the trial. All participants also received supportive care reflecting
local practice and national guidelines.

The main goal of the trial was to compare the health status of
participants seven days after beginning treatment with hIVIG plus
remdesivir with that of participants seven days after beginning treatment
with remdesivir alone. The primary endpoint was an ordinal outcome with
seven mutually exclusive categories ranging from no limiting symptoms due
to COVID-19, to death. Safety was assessed at day seven with a composite outcome that included death, serious adverse events including organ
failure and serious infections, and severe events that made performing
basic functions impossible.

The ITAC investigators found that participants who received hIVIG
plus remdesivir did not have better health status seven days after
beginning treatment compared with participants who received remdesivir
alone. Similarly, participants who received hIVIG plus remdesivir had
no improvement in other clinical outcomes during the 28-day follow-up
period compared to those who received remdesivir alone.

The investigators also found no overall difference in safety at day
seven for people who received hIVIG plus remdesivir compared to those
who received remdesivir alone. However, the researchers additionally
undertook a pre- specified subgroup analysis of safety among participants
who had developed SARS-CoV-2 neutralizing antibodies before receiving
hIVIG. In this group, the odds of a worse safety outcome at day seven
were 1.6 times as high for people who received hIVIG as for those who
did not. Further research is needed to understand why. The difference
was no longer apparent at day 28.

The ITAC trial was associated with the Accelerating
COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
public-private partnership. Further information about the
trial is available in this NIAID press release (https:// www.niaid.nih.gov/news-events/nih-clinical-trial-testing-hyperimmune- intravenous-immunoglobulin-plus-remdesivir-treat) and at
ClinicalTrials.gov under study identifier NCT04546581.

========================================================================== Story Source: Materials provided by NIH/National_Institute_of_Allergy_and_Infectious Diseases. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Mark N. Polizzotto, Jacqueline Nordwall, Abdel G. Babiker, Andrew
Phillips, David M. Vock, Nnakelu Eriobu, Vivian Kwaghe, Roger
Paredes, Lourdes Mateu, Srikanth Ramachandruni, Rajeev Narang,
Mamta K. Jain, Susana M. Lazarte, Jason V. Baker, Anne E.P. Frosch,
Garyfallia Poulakou, Konstantinos N. Syrigos, Gretchen S. Arnoczy,
Natalie A. McBride, Philip A. Robinson, Farjad Sarafian, Sanjay
Bhagani, Hassan S. Taha, Thomas Benfield, Sean T.H. Liu, Anastasia
Antoniadou, Jens Ulrik Staehr Jensen, Ioannis Kalomenidis,
Adityo Susilo, Prasetyo Hariadi, Tomas O. Jensen MD, Jose Luis
Morales-Rull, Marie Helleberg, Sreenath Meegada, Isik S.

Johansen, Daniel Canario, Eduardo Ferna'ndez-Cruz, Simeon
Metallidis, Amish Shah, Aki Sakurai, Nikolaos G. Koulouris, Robin
Trotman, Amy C.

Weintrob, Daria Podlekareva, Usman Hadi, Kathryn M. Lloyd, Birgit
Thorup Ro/ge, Sho Saito, Kelly Sweerus, Jakob J. Malin, Christoph
Lu"bbert, Jose Mun~oz, Matthew J. Cummings, Marcelo H. Losso,
Dan Turner, Kathryn Shaw- Saliba, Robin Dewar, Helene Highbarger,
Perrine Lallemand, Tauseef Rehman, Norman Gerry, Dona Arlinda,
Christina C. Chang, Birgit Grund, Michael R. Holbrook, Horace
P. Holley, Fleur Hudson, Laura A. McNay, Daniel D. Murray, Sarah
L. Pett, Megan Shaughnessy, Mary C. Smolskis, Giota Touloumi,
Mary E. Wright, Mittie K. Doyle, Sharon Popik, Christine Hall,
Roshan Ramanathan, Huyen Cao, Elsa Mondou, Todd Willis, Joseph V.

Thakuria, Leman Yel, Elizabeth Higgs, Virginia L. Kan, Jens
D. Lundgren, James D. Neaton, H. Clifford Lane. Hyperimmune
immunoglobulin for hospitalised patients with COVID-19 (ITAC): a
double-blind, placebo- controlled, phase 3, randomised trial. The
Lancet, 2022; DOI: 10.1016/ S0140-6736(22)00101-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220128085805.htm

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