Clinical trial NCT05780268: LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)
Official title: 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))
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
name: University of Copenhagen
name: Medical Research Council
name: Kirby Institute
name: Washington D.C. Veterans Affairs Medical Center
name: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
name: National Heart, Lung, and Blood Institute (NHLBI)
name: US Department of Veterans Affairs
name: Prevention and Early Treatment of Acute Lung Injury
name: Cardiothoracic Surgical Trials Network
name: Eli Lilly and Company
name: University of Minnesota
First posted: 2023-03-22
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Sustained Recovery
timeFrame: Through Day 90
measure: Number of Participants With an Ordinal Outcome on Day 5
timeFrame: Status on Day 5
Secondary outcomes:
measure: Number of Participants Who Died From All Causes
timeFrame: Through Day 90
measure: Number of Participants With a Safety Outcome Through Day 5
timeFrame: Through Day 5
measure: Number of Participants With a Safety Outcome Through Day 28
timeFrame: Through Day 28
measure: Number of Participants With a Safety Outcome Through Day 90
timeFrame: Through Day 90
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
state: Arizona
city: Fresno
country: United States
facility: Community Regional Medical Center (Site 203-005), 2823 Fresno Street
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC (Site 074-002), 4150 Clement St.
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.
state: California
city: Stanford
country: United States
facility: Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
state: Colorado
city: Denver
country: United States
facility: Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)
state: Colorado
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW
state: District of Columbia
city: Miami
country: United States
facility: Miami VAMC (Site 074-003), 1201 NW 16 Street
state: Florida
city: Atlanta
country: United States
facility: Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center (Site 301-019), 22 South Greene Street
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (Site 202-002), 55 Fruit Street
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center (Site 201-001), 759 Chestnut Street
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan (Site 205-001), 1500 East Medical Center Drive
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin Healthcare (Site 027-001), 701 Park Avenue
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center (Site 202-005), 2500 North State Street
state: Mississippi
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
state: New York
city: Durham
country: United States
facility: Duke University Hospital (Site 301-006), 2301 Erwin Road
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
state: Ohio
city: Garfield Heights
country: United States
facility: Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
state: Texas
city: Dallas
country: United States
facility: Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health Systems (Site 301-021), 1215 Lee Street
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center (Site 208-001), 325 9th Avenue
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street
state: Washington
city: Morgantown
country: United States
facility: West Virginia University (Site 301-023), One Medical Center Drive
state: West Virginia
city: Aalborg
country: Denmark
facility: Aalborg Hospital (Site 625-005), Hobrovej 18
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
city: Copenhagen Ø
country: Denmark
facility: Righospitalet (Site 625-006), Blegdamsvej 9,
city: Herlev
country: Denmark
facility: Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30
city: Kolding
country: Denmark
facility: Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
city: Odense
country: Denmark
facility: Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN
city: Madrid
country: Spain
facility: UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal
Study officials:
affiliation: INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
name: Jens Lundgren, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: INSIGHT Statistical and Data Management Center, University of Minnesota
name: James Neaton, Prof.
role: STUDY_CHAIR
References:
citation: 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.