A Phase 4 interventional study of Lilly Bamlanivimab and Regeneron Casirivimab + Imdevimab in Covid19, sponsored by Erin McCreary. Terminated at 1 site in United States. Open to participants aged 12 Years to 120 Years. Per ClinicalTrials.gov, last updated 2023-06-15.
Sponsored by Erin McCreary · Phase 4, Interventional, and Other
Multiple monoclonal antibodies (mABs) have been shown to reduce viral burden and improve clinical outcomes, have been granted FDA Emergency Use Authorization (EUA) for use in select populations, and are routinely used in the UPMC Health System, which has made expanded access a priority. However, the comparative effectiveness of these mABS is unknown. The National Academies of Sciences, Engineering, and Medicine has called for expanded access and clinical use of mABs, noting it is "critical to collect data and evaluate whether they are working as predicted". This pragmatic evaluation will determine the relative effects of the EUA-governed mABs versus each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mABs will accordingly change.
While COVID-19 vaccination will reduce COVID-19-related morbidity and mortality, the learned immune response may vary between individuals. This means interventions such as monoclonal antibodies (mAB) will still be needed to prevent progression of COVID-19 illness. Monoclonal antibodies seek to mimic or enhance the natural immune system response against a pathogen and are often used in the care of patients with cancer or infection.
For viral infections, mABs are created by exposing a white blood cell to a particular viral protein, which is then cloned to mass produce antibodies to target that virus. For SARS-CoV-2, the virus that causes COVID-19, IgG1 mABs target the spike protein of SARS-CoV-2 and block viral attachment and entry into cells.
The SARS-CoV-2 mABs bamlanivimab and etesevimab, and the REGN-COV2 combination (casirivimab + imdevimab) reduce nasopharyngeal viral burden plus clinical outcomes including future emergency department visits and hospitalizations. Each received FDA Emergency Use Authorization (EUA) for use in selected populations.
As of February 2021, there are over 60,000 new cases of COVID-19 diagnosed daily in the US, with over 7000 daily COVID-19 related hospital admissions. Although case volumes are currently declining, COVID-19 remains a significant public health threat.
Despite the EUAs, the clinical use of mABs is low due in part to lack of patient access, complexities in drug allocation, and lack of knowledge among providers are contributing factors. Further, the comparative effectiveness of different mABs is unknown and not yet directly studied. The National Academies of Sciences, Engineering, and Medicine recently called for expanded access and clinical use of mABs, noting it is "critical to collect data and evaluate whether they are working as predicted". This evaluation seeks to determine their relative effects versus each other, starting with those governed by EUAs.
OPTIMISE-C19 is a quality improvement (QI) study, governed by approvals from both the UPMC QI committee and the University of Pittsburgh IRB. Currently, mAB therapy is approved for use under EUA issued by the FDA. There are no data on the relative benefits of one mAB versus any other. mABs are ordered by UPMC physicians as a generic referral order and the order is filled by UPMC pharmacy via therapeutic interchange. The selection of mABs available within pharmacy is overseen by the UPMC pharmacy and therapeutics committee. OPTIMISE-C19 provides the therapeutic interchange via random allocation. The UPMC Quality Improvement Committee approved the OPTIMISE-C19 study, including the random therapeutic interchange. The University of Pittsburgh IRB considered the randomized therapeutic interchange to be quality improvement and approved the additional data collection and analyses.
Patients provide verbal consent to receive mAB therapy. UPMC requires physicians to provide and review with patients the EUA Fact Sheet for each mAB, and explain that the patient could receive any of the EUA-governed mABs. As per EUA requirements, physicians discuss the risks and benefits of mABs with patients, and patients consent to receive a mAB as part of routine care, should they desire mAB treatment. Patients are told which mAB they are receiving, and physicians and patients can agree to the assigned mAB or request a specific mAB. It is the treating physicians' and patients' choice to accept the assigned mAB or not. The QI committee considered these steps to represent adequate consent to participate. The IRB considered that the provision of mAB therapy therefore fell under quality improvement and only the additional data collection and analyses represented research. The IRB waived any additional consent requirements.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 4,571 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →This is the only study on the registry with Erin McCreary as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
The Lilly monoclonal antibody bamlanivimab will be administered according to FDA EUA guidelines. Dosing is 700 mg intravenously times one within 10 days of COVID-19 symptom onset.
Biological: Lilly Bamlanivimab
The Regeneron monoclonal antibody cocktail Casirivimab + Imdevimab will be administered according to FDA EUA guidelines. Dosing is 1200 mg of each drug (2400 mg total) administered intravenously times one within 10 days of COVID-19 symptom onset.
Biological: Regeneron Casirivimab + Imdevimab
The Lilly monoclonal antibody cocktail of bamlanivimab + etesevimab will be administered according to FDA EUA guidelines. Dosing is given intravenously times one within 10 days of COVID-19 symptom onset.
Biological: Lilly Bamlanivimab + Etesevimab
The monoclonal antibody of sotrovimab will be administered according to FDA EUA guidelines. Dosing is given intravenously times one within 7 days of COVID-19 symptom onset.
Biological: Sotrovimab
The monoclonal antibody of bebtelovimab will be administered according to FDA EUA guidelines. Dosing is given intravenously times one within 7 days of COVID-19 symptom onset.
Biological: Bebtelovimab
Administration of Lilly Bamlanivimab to COVID positive patients
Administration of Regeneron Casirivimab + Imdevimab to COVID positive patients
Administration of Lilly Bamlanivimab + Etesevimab to COVID positive patients
Administration of Sotrovimab to COVID positive patients
Administration of Bebtelovimab to COVID positive patients
Hospital-free Days
Days alive and free from hospitalization. Patients that are both living and not in the hospital will meet criteria to be counted in this outcome. Deaths were rare and therefore the upper and lower end of the IQR are both 28, in addition to the median. This outcome measure does reflect median hospital free days and interquartile ranges for all groups.
Time frame: 28 days after initial participation
All-cause Mortality at 28 Days
All-cause mortality at 28 days.
Time frame: 28 days after initial participation
SARS-CoV-2 Nasopharyngeal Viral Loads
Where feasible SARS-CoV-2 nasopharyngeal viral loads among participants from baseline and longitudinally through day 28
Time frame: 28 days after initial participation
SARS-CoV-2 Plasma Viral Loads
Where feasible SARS-CoV-2 plasma viral loads among participants from baseline and longitudinally through day 28
Time frame: 28 days after initial participation
SARS-CoV-2 Antibody Titers
Where feasible SARS-CoV-2 antibody titers at baseline and longitudinally through day 28
Time frame: 28 days after initial participation
SARS-CoV-2 Antibody Neutralization
Where feasible SARS-CoV-2 antibody neutralization at baseline and longitudinally through day 28
Time frame: 28 days after initial participation
SARS-CoV-2 Immune Responses
Where feasible SARS-CoV-2 immune responses at baseline and longitudinally through day 28
Time frame: 28 days after initial participation
Detection of SARS-CoV-2 Variants Through Next-generation Sequencing
Where feasible detection of SARS-CoV-2 variants through next-generation sequencing at baseline and longitudinally through day 28
Time frame: 28 days after initial participation
Duration of SAR-CoV-2 Infectivity
Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
Time frame: 28 days after initial participation
Non-culture Surrogates for SARS-CoV-2 Infectivity
Where feasible determining non-culture surrogates for SARS-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
Time frame: 28 days after initial participation
Non-culture Surrogates for SARS-CoV-2 Infectivity
Where feasible determining non-culture surrogates for SARS-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
Time frame: 90 days after initial participation
Duration of SAR-CoV-2 Infectivity
Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
Time frame: 90 days after initial participation
ED Visit Within 28 Days
Time frame: Duration of study
| Milestone | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab |
|---|---|---|---|---|
| Started | 128 | 2454 | 885 | 1104 |
| Completed | 128 | 2454 | 885 | 1104 |
| Not completed | 0 | 0 | 0 | 0 |
Days alive and free from hospitalization. Patients that are both living and not in the hospital will meet criteria to be counted in this outcome. Deaths were rare and therefore the upper and lower end of the IQR are both 28, in addition to the median. This outcome measure does reflect median hospital free days and interquartile ranges for all groups.
| days | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab |
|---|---|---|---|---|
| Hospital-free Days | 28 (28 to 28) | 28 (28 to 28) | 28 (28 to 28) | 28 (28 to 28) |
All-cause mortality at 28 days.
| Participants | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab |
|---|---|---|---|---|
| All-cause Mortality at 28 Days | 1 | 12 | 7 | 7 |
Where feasible SARS-CoV-2 nasopharyngeal viral loads among participants from baseline and longitudinally through day 28
No measurements were reported for this outcome.
Where feasible SARS-CoV-2 plasma viral loads among participants from baseline and longitudinally through day 28
No measurements were reported for this outcome.
Where feasible SARS-CoV-2 antibody titers at baseline and longitudinally through day 28
No measurements were reported for this outcome.
Where feasible SARS-CoV-2 antibody neutralization at baseline and longitudinally through day 28
No measurements were reported for this outcome.
Where feasible SARS-CoV-2 immune responses at baseline and longitudinally through day 28
No measurements were reported for this outcome.
Where feasible detection of SARS-CoV-2 variants through next-generation sequencing at baseline and longitudinally through day 28
No measurements were reported for this outcome.
Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
No measurements were reported for this outcome.
Where feasible determining non-culture surrogates for SARS-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
No measurements were reported for this outcome.
Where feasible determining non-culture surrogates for SARS-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
No measurements were reported for this outcome.
Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lilly Bamlanivimab | 1/128 (0.8%) | 0/128 (0%) | 0/128 (0%) |
| Regeneron Casirivimab + Imdevimab | 12/2,454 (0.5%) | 7/2,454 (0.3%) | 17/2,454 (0.7%) |
| Lilly Bamlanivimab + Etesevimab | 7/885 (0.8%) | 0/885 (0%) | 12/885 (1.4%) |
| Sotrovimab | 7/1,104 (0.6%) | 4/1,104 (0.4%) | 6/1,104 (0.5%) |
| Event | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab |
|---|---|---|---|---|
| other infusion reactionProduct Issues | 0/128 | 5/2454 | 0/885 | 2/1104 |
| chest painCardiac disorders | 0/128 | 2/2454 | 0/885 | 2/1104 |
| Event | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab |
|---|---|---|---|---|
| infusion reactionProduct Issues | 0/128 | 17/2454 | 12/885 | 6/1104 |
| Age, Continuous(years) | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab | Total |
|---|---|---|---|---|---|
| Mean | 57 ± 17 | 54 ± 18 | 56 ± 16 | 53 ± 18 | 54 ± 18 |
| Sex: Female, Male(Participants) | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab | Total |
|---|---|---|---|---|---|
| Female | 69 | 1320 | 470 | 599 | 2458 |
| Male | 59 | 1134 | 415 | 505 | 2113 |
| Race (NIH/OMB)(Participants) | Lilly Bamlanivimab | Regeneron Casirivimab + Imdevimab | Lilly Bamlanivimab + Etesevimab | Sotrovimab | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 15 | 252 | 148 | 161 | 576 |
| White | 104 | 2089 | 693 | 892 | 3778 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 9 | 113 | 44 | 51 | 217 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — De-identified participant-level data underlying the results reported in journal articles, subject to appropriate security controls, may be available for sharing with other researchers.
Supporting information: Sap
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