UPMC OPTIMISE-C19 Trial, a COVID-19 Study

NCT ID: NCT04790786

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 4571 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-10
• Study Completion Date: 2022-06-16

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Lilly Bamlanivimab

Intervention Type: BIOLOGICAL

Administration of Lilly Bamlanivimab to COVID positive patients

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.

Group Type: EXPERIMENTAL

Regeneron Casirivimab + Imdevimab

Intervention Type: BIOLOGICAL

Administration of Regeneron Casirivimab + Imdevimab to COVID positive patients

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.

Group Type: EXPERIMENTAL

Lilly Bamlanivimab + Etesevimab

Intervention Type: BIOLOGICAL

Administration of Lilly Bamlanivimab + Etesevimab to COVID positive patients

Sotrovimab

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.

Group Type: EXPERIMENTAL

Sotrovimab

Intervention Type: BIOLOGICAL

Administration of Sotrovimab to COVID positive patients

Bebtelovimab

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.

Group Type: EXPERIMENTAL

Bebtelovimab

Intervention Type: BIOLOGICAL

Administration of Bebtelovimab to COVID positive patients

Interventions

Lilly Bamlanivimab

Administration of Lilly Bamlanivimab to COVID positive patients

Intervention Type: BIOLOGICAL

Regeneron Casirivimab + Imdevimab

Administration of Regeneron Casirivimab + Imdevimab to COVID positive patients

Intervention Type: BIOLOGICAL

Lilly Bamlanivimab + Etesevimab

Administration of Lilly Bamlanivimab + Etesevimab to COVID positive patients

Intervention Type: BIOLOGICAL

Sotrovimab

Administration of Sotrovimab to COVID positive patients

Intervention Type: BIOLOGICAL

Bebtelovimab

Administration of Bebtelovimab to COVID positive patients

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Erin McCreary

OTHER

Sponsor Role: lead

Responsible Party

Erin McCreary

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Erin McCreary, PharmD

Role: STUDY_DIRECTOR

University of Pittsburgh

David T Huang, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35834252 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35713300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35697146 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34034784 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan: Bam-etes vs bam

View Document

Document Type: Statistical Analysis Plan: cas-imd

View Document

Other Identifiers

STUDY21020179

Identifier Type: -

Identifier Source: org_study_id