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

NCT ID: NCT05780268

Last Updated: 2023-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-05
• Study Completion Date: 2021-02-01

Brief Summary

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.

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.

Conditions

COVID-19

Keywords

COVID-19; COVID 19; Coronaviridae Infections; Coronavirus Infections; RNA Virus Infections; Virus Diseases; Nidovirales Infections; SARS-CoV-2; SARS Coronavirus; ACTIV-3; ACTIV3; TICO

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

LY3819253

Intervention Type: BIOLOGICAL

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

Remdesivir

Intervention Type: BIOLOGICAL

Antiviral agent

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Commercially available 0.9% sodium chloride solution

Remdesivir

Intervention Type: BIOLOGICAL

Antiviral agent

Interventions

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

Intervention Type: BIOLOGICAL

Placebo

Commercially available 0.9% sodium chloride solution

Intervention Type: BIOLOGICAL

Remdesivir

Antiviral agent

Intervention Type: BIOLOGICAL

Other Intervention Names

Veklury

Eligibility Criteria

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

NETWORK

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

Kirby Institute

OTHER_GOV

Sponsor Role: collaborator

Washington D.C. Veterans Affairs Medical Center

FED

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

Prevention and Early Treatment of Acute Lung Injury

OTHER

Sponsor Role: collaborator

Cardiothoracic Surgical Trials Network

OTHER

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jens Lundgren, Prof.

Role: PRINCIPAL_INVESTIGATOR

INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen

James Neaton, Prof.

Role: STUDY_CHAIR

INSIGHT Statistical and Data Management Center, University of Minnesota

Locations

Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue

Tucson, Arizona, United States

Community Regional Medical Center (Site 203-005), 2823 Fresno Street

Fresno, California, United States

Keck Hospital of USC (Site 301-020), 1500 San Pablo Street

Los Angeles, California, United States

UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.

San Francisco, California, United States

San Francisco VAMC (Site 074-002), 4150 Clement St.

San Francisco, California, United States

UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.

San Francisco, California, United States

Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.

Stanford, California, United States

University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue

Aurora, Colorado, United States

Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)

Denver, Colorado, United States

MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW

Washington D.C., District of Columbia, United States

Miami VAMC (Site 074-003), 1201 NW 16 Street

Miami, Florida, United States

Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE

Atlanta, Georgia, United States

University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.

Lexington, Kentucky, United States

Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway

New Orleans, Louisiana, United States

University of Maryland Medical Center (Site 301-019), 22 South Greene Street

Baltimore, Maryland, United States

Massachusetts General Hospital (Site 202-002), 55 Fruit Street

Boston, Massachusetts, United States

Baystate Medical Center (Site 201-001), 759 Chestnut Street

Springfield, Massachusetts, United States

University of Michigan (Site 205-001), 1500 East Medical Center Drive

Ann Arbor, Michigan, United States

Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.

Detroit, Michigan, United States

Hennepin Healthcare (Site 027-001), 701 Park Avenue

Minneapolis, Minnesota, United States

University of Mississippi Medical Center (Site 202-005), 2500 North State Street

Jackson, Mississippi, United States

Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive

Lebanon, New Hampshire, United States

Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road

The Bronx, New York, United States

Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street

The Bronx, New York, United States

Duke University Hospital (Site 301-006), 2301 Erwin Road

Durham, North Carolina, United States

Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd

Winston-Salem, North Carolina, United States

Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue

Cleveland, Ohio, United States

Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue

Cleveland, Ohio, United States

Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road

Garfield Heights, Ohio, United States

Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.

Portland, Oregon, United States

Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive

Nashville, Tennessee, United States

UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor

Dallas, Texas, United States

Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.

Dallas, Texas, United States

Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street

Houston, Texas, United States

Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.

Houston, Texas, United States

Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street

Murray, Utah, United States

University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207

Salt Lake City, Utah, United States

University of Virginia Health Systems (Site 301-021), 1215 Lee Street

Charlottesville, Virginia, United States

Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street

Richmond, Virginia, United States

Harborview Medical Center (Site 208-001), 325 9th Avenue

Seattle, Washington, United States

University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street

Seattle, Washington, United States

West Virginia University (Site 301-023), One Medical Center Drive

Morgantown, West Virginia, United States

Aalborg Hospital (Site 625-005), Hobrovej 18

Aalborg, , Denmark

Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99

Aarhus N, , Denmark

Righospitalet (Site 625-006), Blegdamsvej 9,

Copenhagen Ø, , Denmark

Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75

Herlev, , Denmark

Nordsjællands Hospital (Site 625-009), Dyrehavevej 29

Hillerød, , Denmark

Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30

Hvidovre, , Denmark

Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24

Kolding, , Denmark

Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4

Odense, , Denmark

Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng

Singapore, , Singapore

Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n

Badalona, Barcelona, Spain

Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29

Barcelona, , Spain

Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170

Barcelona, , Spain

Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46

Madrid, , Spain

Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN

Madrid, , Spain

UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal

Madrid, , Spain

Countries

United States; Denmark; Singapore; Spain

References

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.

Reference Type: RESULT

PMID: 33356051 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Trial H1 Protocol

View Document

Document Type: Study Protocol: Master Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

014/ACTIV-3/H1

Identifier Type: -

Identifier Source: org_study_id