UPMC OPTIMISE-C19 Trial, a COVID-19 Study

NCT04790786 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: STUDY21020179
• Study Type: interventional
• Target: 4,571
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Keywords

COVID; monoclonal antibodies

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days after initial participation

Secondary Outcomes (12)

• All-cause Mortality at 28 Days

  28 days after initial participation

• SARS-CoV-2 Nasopharyngeal Viral Loads

  28 days after initial participation

• SARS-CoV-2 Plasma Viral Loads

  28 days after initial participation

• SARS-CoV-2 Antibody Titers

  28 days after initial participation

• SARS-CoV-2 Antibody Neutralization

  28 days after initial participation

Study Arms (5)

Lilly Bamlanivimab

EXPERIMENTAL

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

Regeneron Casirivimab + Imdevimab

EXPERIMENTAL

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

Lilly Bamlanivimab + Etesevimab

EXPERIMENTAL

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

Sotrovimab

EXPERIMENTAL

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

Bebtelovimab

EXPERIMENTAL

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

Interventions

Lilly Bamlanivimab BIOLOGICAL

Administration of Lilly Bamlanivimab to COVID positive patients

Lilly Bamlanivimab

Regeneron Casirivimab + Imdevimab BIOLOGICAL

Administration of Regeneron Casirivimab + Imdevimab to COVID positive patients

Regeneron Casirivimab + Imdevimab

Lilly Bamlanivimab + Etesevimab BIOLOGICAL

Administration of Lilly Bamlanivimab + Etesevimab to COVID positive patients

Lilly Bamlanivimab + Etesevimab

Sotrovimab BIOLOGICAL

Administration of Sotrovimab to COVID positive patients

Sotrovimab

Bebtelovimab BIOLOGICAL

Administration of Bebtelovimab to COVID positive patients

Bebtelovimab

Eligibility Criteria

• Age: 12 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Erin McCreary: lead
• University of Pittsburgh: collaborator

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (5)

• 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.

  PMID: 35834252 DERIVED

• 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.

  PMID: 35713300 DERIVED

• 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.

  PMID: 35697146 DERIVED

• 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.

  PMID: 34473343 DERIVED

• 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.

  PMID: 34034784 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

imdevimab; etesevimab; sotrovimab; bebtelovimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Results are presented before any prespecified statistical trigger was reached. Lack of patient-level variant data limited ability to assess comparative effectiveness relative to variant strains. The EHR eligibility screen identified most, but not all, EUA risk factors and could not identify if a patient was asymptomatic or severely ill. Finally, vaccination status was unable to be ascertained for this cohort which may impact effectiveness of monoclonal antibody therapy.

Results Point of Contact

• Title: Erin McCreary
• Organization: UPMC

mccrearye3@upmc.edu

4845159589

Study Officials

• Erin McCreary, PharmD

  University of Pittsburgh

  STUDY DIRECTOR

• David T Huang, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 10, 2021
• Study Start: March 10, 2021
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: June 15, 2023
• Results First Posted: June 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (1)