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

Primary Purpose

Covid19

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Lilly Bamlanivimab
Regeneron Casirivimab + Imdevimab
Lilly Bamlanivimab + Etesevimab
Sotrovimab
Bebtelovimab
Sponsored by
Erin McCreary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Covid19 focused on measuring COVID, monoclonal antibodies

Eligibility Criteria

12 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UPMC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Lilly Bamlanivimab

Regeneron Casirivimab + Imdevimab

Lilly Bamlanivimab + Etesevimab

Sotrovimab

Bebtelovimab

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

All-cause Mortality at 28 Days
All-cause mortality at 28 days.
SARS-CoV-2 Nasopharyngeal Viral Loads
Where feasible SARS-CoV-2 nasopharyngeal viral loads among participants from baseline and longitudinally through day 28
SARS-CoV-2 Plasma Viral Loads
Where feasible SARS-CoV-2 plasma viral loads among participants from baseline and longitudinally through day 28
SARS-CoV-2 Antibody Titers
Where feasible SARS-CoV-2 antibody titers at baseline and longitudinally through day 28
SARS-CoV-2 Antibody Neutralization
Where feasible SARS-CoV-2 antibody neutralization at baseline and longitudinally through day 28
SARS-CoV-2 Immune Responses
Where feasible SARS-CoV-2 immune responses at baseline and longitudinally through day 28
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
Duration of SAR-CoV-2 Infectivity
Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
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
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
Duration of SAR-CoV-2 Infectivity
Where feasible determining the duration of SAR-CoV-2 infectivity among patients with persistent nasopharyngeal swab viral shedding
ED Visit Within 28 Days

Full Information

First Posted
February 26, 2021
Last Updated
May 21, 2023
Sponsor
Erin McCreary
Collaborators
University of Pittsburgh
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1. Study Identification

Unique Protocol Identification Number
NCT04790786
Brief Title
UPMC OPTIMISE-C19 Trial, a COVID-19 Study
Acronym
OPTIMISE-C19
Official Title
The UPMC OPtimizing Treatment and Impact of Monocolonal antIbodieS Through Evaluation for COVID-19 Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Emergency Use Authorizations for monoclonal antibodies withdrawn
Study Start Date
March 10, 2021 (Actual)
Primary Completion Date
June 16, 2022 (Actual)
Study Completion Date
June 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Erin McCreary
Collaborators
University of Pittsburgh

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
COVID, monoclonal antibodies

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
4571 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lilly Bamlanivimab
Arm Type
Experimental
Arm Description
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.
Arm Title
Regeneron Casirivimab + Imdevimab
Arm Type
Experimental
Arm Description
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.
Arm Title
Lilly Bamlanivimab + Etesevimab
Arm Type
Experimental
Arm Description
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.
Arm Title
Sotrovimab
Arm Type
Experimental
Arm Description
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.
Arm Title
Bebtelovimab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Lilly Bamlanivimab
Intervention Description
Administration of Lilly Bamlanivimab to COVID positive patients
Intervention Type
Biological
Intervention Name(s)
Regeneron Casirivimab + Imdevimab
Intervention Description
Administration of Regeneron Casirivimab + Imdevimab to COVID positive patients
Intervention Type
Biological
Intervention Name(s)
Lilly Bamlanivimab + Etesevimab
Intervention Description
Administration of Lilly Bamlanivimab + Etesevimab to COVID positive patients
Intervention Type
Biological
Intervention Name(s)
Sotrovimab
Intervention Description
Administration of Sotrovimab to COVID positive patients
Intervention Type
Biological
Intervention Name(s)
Bebtelovimab
Intervention Description
Administration of Bebtelovimab to COVID positive patients
Primary Outcome Measure Information:
Title
Hospital-free Days
Description
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
Secondary Outcome Measure Information:
Title
All-cause Mortality at 28 Days
Description
All-cause mortality at 28 days.
Time Frame
28 days after initial participation
Title
SARS-CoV-2 Nasopharyngeal Viral Loads
Description
Where feasible SARS-CoV-2 nasopharyngeal viral loads among participants from baseline and longitudinally through day 28
Time Frame
28 days after initial participation
Title
SARS-CoV-2 Plasma Viral Loads
Description
Where feasible SARS-CoV-2 plasma viral loads among participants from baseline and longitudinally through day 28
Time Frame
28 days after initial participation
Title
SARS-CoV-2 Antibody Titers
Description
Where feasible SARS-CoV-2 antibody titers at baseline and longitudinally through day 28
Time Frame
28 days after initial participation
Title
SARS-CoV-2 Antibody Neutralization
Description
Where feasible SARS-CoV-2 antibody neutralization at baseline and longitudinally through day 28
Time Frame
28 days after initial participation
Title
SARS-CoV-2 Immune Responses
Description
Where feasible SARS-CoV-2 immune responses at baseline and longitudinally through day 28
Time Frame
28 days after initial participation
Title
Detection of SARS-CoV-2 Variants Through Next-generation Sequencing
Description
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
Title
Duration of SAR-CoV-2 Infectivity
Description
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
Title
Non-culture Surrogates for SARS-CoV-2 Infectivity
Description
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
Title
Non-culture Surrogates for SARS-CoV-2 Infectivity
Description
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
Title
Duration of SAR-CoV-2 Infectivity
Description
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
Title
ED Visit Within 28 Days
Time Frame
Duration of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erin McCreary, PharmD
Organizational Affiliation
University of Pittsburgh
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
David T Huang, MD, MPH
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
Relevant data may be available 1 year following publication
IPD Sharing Access Criteria
Data access is subject to a methodologically sound proposal and the necessary data sharing agreements.
Citations:
PubMed Identifier
35834252
Citation
Huang DT, McCreary EK, Bariola JR, Minnier TE, Wadas RJ, Shovel JA, Albin D, Marroquin OC, Kip KE, Collins K, Schmidhofer M, Wisniewski MK, Nace DA, Sullivan C, Axe M, Meyers R, Weissman A, Garrard W, Peck-Palmer OM, Wells A, Bart RD, Yang A, Berry LR, Berry S, Crawford AM, McGlothlin A, Khadem T, Linstrum K, Montgomery SK, Ricketts D, Kennedy JN, Pidro CJ, Nakayama A, Zapf RL, Kip PL, Haidar G, Snyder GM, McVerry BJ, Yealy DM, Angus DC, Seymour CW. Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial. JAMA Netw Open. 2022 Jul 1;5(7):e2220957. doi: 10.1001/jamanetworkopen.2022.20957.
Results Reference
derived
PubMed Identifier
35713300
Citation
Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
Results Reference
derived
PubMed Identifier
35697146
Citation
McCreary EK, Bariola JR, Minnier TE, Wadas RJ, Shovel JA, Albin D, Marroquin OC, Kip KE, Collins K, Schmidhofer M, Wisniewski MK, Nace DA, Sullivan C, Axe M, Meyers R, Weissman A, Garrard W, Peck-Palmer OM, Wells A, Bart RD, Yang A, Berry LR, Berry S, Crawford AM, McGlothlin A, Khadem T, Linstrum K, Montgomery SK, Ricketts D, Kennedy JN, Pidro CJ, Haidar G, Snyder GM, McVerry BJ, Yealy DM, Angus DC, Nakayama A, Zapf RL, Kip PL, Seymour CW, Huang DT. The comparative effectiveness of COVID-19 monoclonal antibodies: A learning health system randomized clinical trial. Contemp Clin Trials. 2022 Aug;119:106822. doi: 10.1016/j.cct.2022.106822. Epub 2022 Jun 11.
Results Reference
derived
PubMed Identifier
34473343
Citation
Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
Results Reference
derived
PubMed Identifier
34034784
Citation
Huang DT, McCreary EK, Bariola JR, Wadas RJ, Kip KE, Marroquin OC, Koscumb S, Collins K, Shovel JA, Schmidhofer M, Wisniewski MK, Sullivan C, Yealy DM, Axe M, Nace DA, Haidar G, Khadem T, Linstrum K, Snyder GM, Seymour CW, Montgomery SK, McVerry BJ, Berry L, Berry S, Meyers R, Weissman A, Peck-Palmer OM, Wells A, Bart R, Albin DL, Minnier T, Angus DC. The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization. Trials. 2021 May 25;22(1):363. doi: 10.1186/s13063-021-05316-3.
Results Reference
derived

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UPMC OPTIMISE-C19 Trial, a COVID-19 Study

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