LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)

A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H1: LY3819253 (LY-CoV555))

This study looks at the safety and effectiveness of LY3819253 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either LY3819253 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H1.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Remdesivir; Biological: LY3819253; Biological: Placebo

Detailed Description

This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of LY3819253 in hospitalized patients infected with COVID-19.

This is a randomized, blinded, controlled sub-study of LY3819253 plus current standard of care (SOC) against placebo plus current SOC. The placebo arm may be shared across other sub-studies of the ACTIV-3/TICO master protocol. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.

Randomization will be stratified by study site pharmacy and disease severity. There are 2 disease severity strata: Participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2).

An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. The pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. At the outset of the trial, only participants in disease severity stratum 1 will be enrolled. This will continue until approximately 300 participants are enrolled and followed for 5 days. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5.

If LY3819253 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. Participants will be followed for 18 months following randomization.

This trial will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Hospital (Site 625-005), Hobrovej 18
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
  • Copenhagen Ø, Denmark, 2100
    • Righospitalet (Site 625-006), Blegdamsvej 9,
  • Herlev, Denmark, 2730
    • Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
  • Hillerød, Denmark, 3400
    • Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30
  • Kolding, Denmark, 6000
    • Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
  • Odense, Denmark, 5000
    • Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng
• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170
  • Madrid, Spain, 28017
    • Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN
  • Madrid, Spain, 28046
    • UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
  • California
    • Fresno, California, United States, 93701
      • Community Regional Medical Center (Site 203-005), 2823 Fresno Street
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
    • San Francisco, California, United States, 94115
      • UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
    • San Francisco, California, United States, 94121
      • San Francisco VAMC (Site 074-002), 4150 Clement St.
    • San Francisco, California, United States, 94143
      • UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.
    • Stanford, California, United States, 94305
      • Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
    • Denver, Colorado, United States, 80204
      • Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW
  • Florida
    • Miami, Florida, United States, 33125
      • Miami VAMC (Site 074-003), 1201 NW 16 Street
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center (Site 301-019), 22 South Greene Street
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital (Site 202-002), 55 Fruit Street
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center (Site 201-001), 759 Chestnut Street
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan (Site 205-001), 1500 East Medical Center Drive
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare (Site 027-001), 701 Park Avenue
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center (Site 202-005), 2500 North State Street
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital (Site 301-006), 2301 Erwin Road
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
  • Ohio
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
    • Garfield Heights, Ohio, United States, 44125
      • Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
    • Dallas, Texas, United States, 75246
      • Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health Systems (Site 301-021), 1215 Lee Street
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center (Site 208-001), 325 9th Avenue
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University (Site 301-023), One Medical Center Drive

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Refer to the master protocol (NCT04501978)

Exclusion Criteria: Refer to the master protocol (NCT04501978)

Additional Criteria:

Non-pregnant female participants who are of reproductive potential and male participants who are able to father a child must abstain from male/female sexual intercourse or agree to use two forms of effective contraception, where at least one form is highly effective (less than 1% failure rate), for the entirety of the study and for 90 days after investigational agent is administered. Highly effective methods of contraception (less than 1% failure rate) include, but are not limited to:

• combination oral contraceptives
• implanted contraceptives
• intrauterine devices

Effective methods of contraception include, but are not limited to:

• diaphragms and cervical caps with spermicide
• cervical sponges
• condoms with spermicide

NOTE:

• Use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these barrier methods are combined.
• Barrier protection methods without concomitant use of a spermicide are not an effective or acceptable method of contraception.
• Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), and withdrawal are not acceptable methods of contraception. Participants not of reproductive potential are eligible without requiring the use of a contraceptive method. Participant-reported history is acceptable documentation of surgical sterilization and menopause. Participants with pregnant partners should use condoms during vaginal intercourse through 90 days after investigational agent administration. Participants should refrain from sperm donation through 90 days after investigational agent administration. NOTE: Reproductive potential is defined as patients who have reached menarche, who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥ 40 IU/ml or 24 consecutive months if an FSH is not available, who have not undergone surgical sterilization, who do not have other clinical condition that could induce amenorrhea, who are not taking medications such as oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators (SERMs) or chemotherapy that could induce amenorrhea. Individuals with permanent infertility due to an alternate medical cause (e.g. Mullerian agenesis, androgen insensitivity), investigator discretion should be applied.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus SOC; Placebo administered by IV infusion; Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion	Biological: Remdesivir; Antiviral agent; Other Names: Veklury; Biological: Placebo; Commercially available 0.9% sodium chloride solution
Experimental: LY3819253 plus SOC; LY3819253 7000 mg solution (10 vials of 20 mL solution containing 700 mg each); administered by IV infusion; Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion	Biological: Remdesivir; Antiviral agent; Other Names: Veklury; Biological: LY3819253; LY3819253 is a neutralizing immunoglobulin G (IgG)-1 monoclonal antibody (mAb) to the receptor binding domain (RBD) of the S protein of SARS-CoV-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Recovery	Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.	Through Day 90
Number of Participants With an Ordinal Outcome on Day 5	Ordinal outcome with 7 mutually exclusive categories	Status on Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Died From All Causes	All-cause mortality	Through Day 90
Number of Participants With a Safety Outcome Through Day 5	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5	Through Day 5
Number of Participants With a Safety Outcome Through Day 28	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28	Through Day 28
Number of Participants With a Safety Outcome Through Day 90	Death, SAE, clinical organ failure, serious infections through Day 90	Through Day 90

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eli Lilly and Company; National Heart, Lung, and Blood Institute (NHLBI); University of Copenhagen; US Department of Veterans Affairs; Medical Research Council; University of Minnesota; AIDS Clinical Trials Group; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); Prevention and Early Treatment of Acute Lung Injury; Cardiothoracic Surgical Trials Network
• Investigators: Principal Investigator: Jens Lundgren, Prof., INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen; Study Chair: James Neaton, Prof., INSIGHT Statistical and Data Management Center, University of Minnesota

Publications and helpful links

General Publications

• ACTIV-3/TICO LY-CoV555 Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Ostergaard L, Chang CC, Davey VJ, Goodman A, Higgs ES, Murray DD, Murray TA, Paredes R, Parmar MKB, Phillips AN, Reilly C, Sharma S, Dewar RL, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD. A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. N Engl J Med. 2021 Mar 11;384(10):905-914. doi: 10.1056/NEJMoa2033130. Epub 2020 Dec 22.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2020
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus Infections; SARS-CoV-2; COVID 19; COVID-19; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; SARS Coronavirus; ACTIV-3; ACTIV3; TICO
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir; Bamlanivimab
• Other Study ID Numbers: 014/ACTIV-3/H1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No