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UPMC OPTIMISE-C19 Trial, a COVID-19 Study (OPTIMISE-C19)

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ClinicalTrials.gov Identifier: NCT04790786
Recruitment Status : Recruiting
First Posted : March 10, 2021
Last Update Posted : July 20, 2021
Sponsor:
Collaborators:
University of Pittsburgh Medical Center
Berry Consultants
Information provided by (Responsible Party):
David T Huang, University of Pittsburgh

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Covid19 Biological: Lilly Bamlanivimab Biological: Regeneron Casirivimab + Imdevimab Biological: Lilly Bamlanivimab + Etesevimab Biological: Sotrovimab Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study is an adaptive platform and as such is intended to study multiple interventions simultaneously, does not have a defined sample size, and is intended to move forward in perpetual fashion with domains and interventions being added and subtracted over time. For example, interventions will be added and subtracted depending on federal decisions regarding monoclonal antibodies, such as granting or revoking authorization for use.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The UPMC OPtimizing Treatment and Impact of Monocolonal antIbodieS Through Evaluation for COVID-19 Trial
Actual Study Start Date : March 10, 2021
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
Experimental: Lilly Bamlanivimab
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
Administration of Lilly Bamlanivimab to COVID positive patients

Experimental: Regeneron Casirivimab + Imdevimab
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
Administration of Regeneron Casirivimab + Imdevimab to COVID positive patients

Experimental: Lilly Bamlanivimab + Etesevimab
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
Administration of Lilly Bamlanivimab + Etesevimab to COVID positive patients

Experimental: Sotrovimab
The monoclonal antibody of sotrovimab will be administered according to FDA EUA guidelines. Dosing is given intravenously times one within 10 days of COVID-19 symptom onset.
Biological: Sotrovimab
Administration of Sotrovimab to COVID positive patients




Primary Outcome Measures :
  1. Alive and Free from Hospitalization [ Time Frame: 28 days after initial participation ]
    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.


Secondary Outcome Measures :
  1. All-location mortality at 90 days [ Time Frame: 90 days after initial participation ]
    All-location mortality at 90 days.

  2. All-location mortality at 28 days [ Time Frame: 28 days after initial participation ]
    All-location mortality at 28 days.

  3. All-cause mortality at 28 days [ Time Frame: 28 days after initial participation ]
    All-cause mortality at 28 days.

  4. All-cause mortality at 90 days [ Time Frame: 90 days after initial participation ]
    All-location mortality at 90 days

  5. Organ-support free days at day 28 [ Time Frame: 28 days after initial participation ]
    Organ-support free days at day 28

  6. SARS-CoV-2 nasopharyngeal viral loads [ Time Frame: 28 days after initial participation ]
    Where feasible SARS-CoV-2 nasopharyngeal viral loads among participants from baseline and longitudinally through day 28

  7. SARS-CoV-2 plasma viral loads [ Time Frame: 28 days after initial participation ]
    Where feasible SARS-CoV-2 plasma viral loads among participants from baseline and longitudinally through day 28

  8. SARS-CoV-2 antibody titers [ Time Frame: 28 days after initial participation ]
    Where feasible SARS-CoV-2 antibody titers at baseline and longitudinally through day 28

  9. SARS-CoV-2 antibody neutralization [ Time Frame: 28 days after initial participation ]
    Where feasible SARS-CoV-2 antibody neutralization at baseline and longitudinally through day 28

  10. SARS-CoV-2 immune responses [ Time Frame: 28 days after initial participation ]
    Where feasible SARS-CoV-2 immune responses at baseline and longitudinally through day 28

  11. Detection of SARS-CoV-2 variants through next-generation sequencing [ Time Frame: 28 days after initial participation ]
    Where feasible detection of SARS-CoV-2 variants through next-generation sequencing at baseline and longitudinally through day 28

  12. Duration of SAR-CoV-2 infectivity [ Time Frame: 28 days after initial participation ]
    Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding

  13. Non-culture surrogates for SARS-CoV-2 infectivity [ Time Frame: 28 days after initial participation ]
    Where feasible determining non-culture surrogates for SARS-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding

  14. Non-culture surrogates for SARS-CoV-2 infectivity [ Time Frame: 90 days after initial participation ]
    Where feasible determining non-culture surrogates for SARS-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding

  15. Duration of SAR-CoV-2 infectivity [ Time Frame: 90 days after initial participation ]
    Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 120 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • COVID-19 positive patients
  • Eligible for mAB under FDA EUA

Exclusion Criteria:

  • Death is deemed to be imminent or inevitable
  • Previous participation in this REMAP within the last 90 days

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04790786


Contacts
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Contact: David T Huang, MD, MPH (412) 647-6818 huangdt@upmc.edu
Contact: Kelsey Linstrum, MS 203-947-6013 linstrumk@upmc.edu

Locations
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United States, Pennsylvania
UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Bryan J McVerry, MD    412-648-3098    mcverrybj@upmc.edu   
Principal Investigator: Derek C Angus, MD, MPH         
Principal Investigator: David T Huang, MD, MPH         
Sponsors and Collaborators
David T Huang
University of Pittsburgh Medical Center
Berry Consultants
Investigators
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Study Director: Bryan McVerry, MD University of Pittsburgh
Principal Investigator: David Huang, MD University of Pittsburgh
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: David T Huang, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04790786    
Other Study ID Numbers: STUDY21020179
First Posted: March 10, 2021    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Relevant data may be available 1 year following publication
Access Criteria: Data access is subject to a methodologically sound proposal and the necessary data sharing agreements.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by David T Huang, University of Pittsburgh:
COVID
monoclonal antibodies