Recently, an international trial site network known as the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) completed a global study revealing that remdesivir plus a highly concentrated solution of antibodies that neutralize SARS-CoV-2 isn’t more effective than remdesivir alone in treating adults hospitalized with COVID-19.
TrialSite provides a brief breakdown of these study results recently published in The Lancet.
What was the name of the study?
Inpatient Treatment with Anti-Coronavirus Immunoglobulin, or ITAC
What organization funded this study?
The National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH). 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 and at ClinicalTrials.gov under study identifier NCT04546581 as reported by the agency in a press release.Subscribe to the Trialsitenews “COVID-19” ChannelNo spam – we promise
Who led the trial (the PI)?
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.
What was the antibody solution used in the study?
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.
What companies produced the hIVIG investigational product?
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.
What were the study details?
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.
What was the trial’s main objective?
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.
What were the trial results?
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 on day 28.
Call to Action: Check out the peer-reviewed, published results.