A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness

NCT04427501 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17947J2W-MC-PYAB
• Study Type: interventional
• Target: 3,307
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 will be given to participants with early symptoms of COVID-19. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone. Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 22), open-label addendum to evaluate the pharmacokinetics and safety of LY3819253 and LY3832479. Enrollment began on March 31, 2021, and completed on September 24, 2021. Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 23), open-label addendum to evaluate the pharmacokinetics and safety of LY3853113. Enrollment began on August 19, 2022, and completed on February 21, 2023.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (7)

• Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization or Death From Any Cause in 2800 mg Bamlanivumab/2800 mg Etesevimab, 700 mg Bamlanivimab/1400mg Etesevimab and Their Placebo Groups

  COVID-19 Related Deterioration (yes/no) was defined as a participant experiencing COVID-19-related hospitalization (defined as 24 hours of acute care) or death from any cause by Day 29.

  Baseline through Day 29

• Phase 3: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than a Prespecified Threshold in Arms 350 mg Bamlanivimab/700 mg Etesevimab and Placebo

  SARS-CoV-2 persistent high viral load (yes/no) was defined as ribonuclease P(RP) normalized viral load \>=5.27 vs otherwise.

  Day 7

• Phase 2: Change From Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load

  SARS-CoV-2 viral load was based on nasopharyngeal swab sampling for reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. If Day 11 SARS-CoV-2 viral load was missing, the earliest measurement closest to the Day 11 visit, but within 4 days (Day 7-Day 15), was used for the Day 11 value. If no measurements were available, the Day 11 viral load was treated as missing at random (MAR) in the analysis. Viral load is reported as normalized viral load and is unitless.

  Baseline, Day 11

• Phase 2: Percentage of Participants Who Experience a Serious Adverse Event(s) SAE(s)

  An SAE was defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other different situations will have medical or scientific judgment to determine if they are SAE. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality are reported in the Adverse Events section.

  Baseline through Day 85

• Phase 3 and Phase 2/3 [Arm 22], Pharmacokinetics (PK): Mean Concentrations of LY3819253 (Bamlanivimab)

  Mean Concentration of Bamlanivimab in the presence of Etesevimab is reported. Due to the limited number of pediatric participants across all study arms in phase 3, PK concentration summary data was combined including phase 3 and phase 2/3 (Pediatric addendum, Arm 22) reporting arms. All pediatric participants from Phase 3 trial arms including Arm 22 who contributed data to the required outcome (PK concentration at Day 29) were included in the PK summary.

  Day 29 Post-dose

• Phase 3 and Phase 2/3 [Arm 22], Pharmacokinetics (PK): Mean Concentrations of LY3832479 (Etesevimab)

  Mean Concentration of Etesevimab in the presence of Bamlanivimab is reported. Due to the limited number of pediatric participants across all study arms in phase 3, PK concentration summary data was combined including phase 3 and phase 2/3 (Pediatric addendum, Arm 22) reporting arms. All pediatric participants from Phase 3 trial arms including Arm 22 who contributed data to the required outcome (PK concentration at Day 29) were included in the PK summary.

  Day 29 Post-dose

• Phase 2/3, PK: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) for Bebtelovimab [Arm 23]

  AUC0-∞ for Bebtelovimab was reported.

  Day 60 Post-dose

Secondary Outcomes (19)

• Phase 3: Percentage of Participants Demonstrating Symptom Resolution

  Day 11

• Phase 3: Percentage of Participants Demonstrating Symptom Improvement

  Day 11

• Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause

  Baseline through Day 85

• Phase 3: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load

  Baseline, Day 7

• Phase 3: Time to Sustained Symptom Resolution

  Baseline through Day 29

Study Arms (5)

LY3819253

EXPERIMENTAL

700 mg, 2800 mg, 7000 mg, LY3819253 administered intravenously (IV)

Drug: LY3819253

LY3819253 + LY3832479

EXPERIMENTAL

350 mg, 700 mg, 2800 mg LY3819253 + 700 mg, 1400 mg, 2800 mg LY3832479 administered IV or subcutaneously (SQ)

Drug: LY3819253; Drug: LY3832479

LY3819253 + LY3832479 (Pediatric Addendum, Arm 22)

EXPERIMENTAL

LY3819253 dose based upon weight (weight Group: ≥40 kilogram (kg) = 700 mg dose, \>20 kg to \<40 kg = 350 mg dose, \>12 kg to 20 kg = 175 mg dose and 1.5 kg to 12 kg = 15 mg/kg dose) and LY3832479 dose based upon weight (weight Group: ≥40 kg = 1400 mg dose, \>20 kg to \<40 kg = 700 mg dose, \>12 kg to 20 kg = 350 mg dose and 1.5 kg to 12 kg = 30 mg/kg dose) administered IV.

Drug: LY3819253; Drug: LY3832479

LY3853113 (Pediatric Addendum, Arm 23)

EXPERIMENTAL

LY3853113 dose based upon weight (Weight Group: ≥3.3 to ≤12 kg = 3 mg/kg dose, \>12 to ≤20 kg = 43.75 mg dose, \>20 to \<40 kg = 87.5 mg dose, ≥40 kg = 175 mg dose) administered IV.

Drug: LY3853113

Placebo

PLACEBO COMPARATOR

Placebo administered IV

Drug: Placebo

Interventions

LY3819253 DRUG

Administered IV

Also known as: LY-CoV555, Bamlanivimab

LY3819253; LY3819253 + LY3832479; LY3819253 + LY3832479 (Pediatric Addendum, Arm 22)

LY3832479 DRUG

Administered IV

Also known as: LY-CoV016, Etesevimab

LY3819253 + LY3832479; LY3819253 + LY3832479 (Pediatric Addendum, Arm 22)

LY3853113 DRUG

Administered IV

Also known as: bebtelovimab

LY3853113 (Pediatric Addendum, Arm 23)

Placebo DRUG

Administered IV

Placebo

Eligibility Criteria

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

You may qualify if:

• Are currently not hospitalized. (Not applicable to participants in treatment arm 22.)
• Have one or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion. (Not applicable to participants in treatment arm 22.)
• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
• Are males or females, including pregnant females who agree to contraceptive requirements
• Understand and agree to comply with planned study procedures
• Agree to the collection of nasopharyngeal swabs and venous blood. (Not applicable to participants in treatment arms 20-21.)
• The participant or legally authorized representative give signed informed consent and/or assent
• Participants in treatment arms 7-9, 13-14, and 18-21 ONLY
• Are greater than or equal to (≥)18 years of age and must satisfy at least one of the following at the time of screening
• Are pregnant
• Are ≥65 years of age
• Have a body mass index (BMI) ≥35
• Have chronic kidney disease (CKD)
• Have type 1 or type 2 diabetes
• Have immunosuppressive disease

You may not qualify if:

• Have oxygen saturation (SpO2) less than or equal to (≤)93 percent (%) on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) less than (\<)300, respiratory rate greater than or equal to (≥)30 per minute, heart rate ≥125 per minute due to COVID-19
• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
• Have known allergies to any of the components used in the formulation of the interventions
• Have hemodynamic instability requiring use of pressors within 24 hours of randomization
• Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
• Have any co-morbidity requiring surgery within \<7 days, or that is considered life-threatening within 29 days
• Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study
• Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study
• Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing
• Have received treatment with a SARS-CoV-2 specific monoclonal antibody
• Have received convalescent COVID-19 plasma treatment
• Have participated in a previous SARS-CoV-2 vaccine study or have received a SARS-CoV-2 vaccine
• Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed
• Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Mothers who are breast feeding

Sponsors & Collaborators

• Eli Lilly and Company: lead
• AbCellera Biologics Inc.: collaborator
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (12)

Clinnova Research - Redondo Beach

Redondo Beach, California, 90277, United States

Location

Bio-Medical Research, LLC

Miami, Florida, 33184, United States

Location

Rophe Adult and Pediatric Medicine

Union City, Georgia, 30291, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

U of MA Mem Med Ctr

Worcester, Massachusetts, 01655, United States

Location

Great Lakes Research Group, Inc.

Bay City, Michigan, 48706, United States

Location

Childrens Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Sky Clinical Prime and Health Wellness Clinic

Fayette, Mississippi, 39069, United States

Location

Sky Clin Resch - Quinn HC

Ridgeland, Mississippi, 39157, United States

Location

Monroe Biomed Research

Monroe, North Carolina, 28112, United States

Location

B S & W Med Center

Dallas, Texas, 75246, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

Related Publications (11)

• Patel DR, Macpherson L, Bohm M, Upadhyaya H, Deveau C, Nirula A, Klekotka P, Williams M, Hufford MM. Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19. Infect Dis Ther. 2024 Oct;13(10):2123-2134. doi: 10.1007/s40121-024-01031-z. Epub 2024 Sep 4.

  PMID: 39230829 DERIVED

• Upadhyaya HP, Chien JY, Long AJ, Bohm MS, Kallewaard NL, Macpherson LF, Patel DR, Hufford MM, Krull CJ, Ang JY, Chen P, Muller WJ, Potts JA, Quinn T, Williams M; BLAZE-1 Investigators. Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial. Infect Dis Ther. 2023 Jul;12(7):1861-1873. doi: 10.1007/s40121-023-00832-y. Epub 2023 Jun 17.

  PMID: 37329415 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

• Chen P, Behre G, Hebert C, Kumar P, Farmer Macpherson L, Graham-Clarke PL, De La Torre I, Nichols RM, Hufford MM, Patel DR, Naegeli AN. Bamlanivimab and Etesevimab Improve Symptoms and Associated Outcomes in Ambulatory Patients at Increased Risk for Severe Coronavirus Disease 2019: Results From the Placebo-Controlled Double-Blind Phase 3 BLAZE-1 Trial. Open Forum Infect Dis. 2022 Apr 7;9(5):ofac172. doi: 10.1093/ofid/ofac172. eCollection 2022 May.

  PMID: 35493124 DERIVED

• Dougan M, Azizad M, Mocherla B, Gottlieb RL, Chen P, Hebert C, Perry R, Boscia J, Heller B, Morris J, Crystal C, Igbinadolor A, Huhn G, Cardona J, Shawa I, Kumar P, Blomkalns A, Adams AC, Van Naarden J, Custer KL, Knorr J, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Sabo J, Patel DR, Dabora MC, Williams M, Klekotka P, Shen L, Skovronsky DM, Nirula A. A Randomized, Placebo-Controlled Clinical Trial of Bamlanivimab and Etesevimab Together in High-Risk Ambulatory Patients With COVID-19 and Validation of the Prognostic Value of Persistently High Viral Load. Clin Infect Dis. 2022 Aug 24;75(1):e440-e449. doi: 10.1093/cid/ciab912.

  PMID: 34718468 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

• Nathan R, Shawa I, De La Torre I, Pustizzi JM, Haustrup N, Patel DR, Huhn G. A Narrative Review of the Clinical Practicalities of Bamlanivimab and Etesevimab Antibody Therapies for SARS-CoV-2. Infect Dis Ther. 2021 Dec;10(4):1933-1947. doi: 10.1007/s40121-021-00515-6. Epub 2021 Aug 10.

  PMID: 34374951 DERIVED

• Meng X, Wang P, Xiong Y, Wu Y, Lin X, Lu S, Li R, Zhao B, Liu J, Zeng S, Zeng L, Wu Y, Lu Y, Zhang J, Liu D, Wang S, Lu H. Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: a Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody. Emerg Microbes Infect. 2021 Dec;10(1):1638-1648. doi: 10.1080/22221751.2021.1960900.

  PMID: 34346827 DERIVED

• Dougan M, Nirula A, Azizad M, Mocherla B, Gottlieb RL, Chen P, Hebert C, Perry R, Boscia J, Heller B, Morris J, Crystal C, Igbinadolor A, Huhn G, Cardona J, Shawa I, Kumar P, Adams AC, Van Naarden J, Custer KL, Durante M, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Kallewaard NL, Sabo J, Patel DR, Dabora MC, Klekotka P, Shen L, Skovronsky DM; BLAZE-1 Investigators. Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19. N Engl J Med. 2021 Oct 7;385(15):1382-1392. doi: 10.1056/NEJMoa2102685. Epub 2021 Jul 14.

  PMID: 34260849 DERIVED

• Gottlieb RL, Nirula A, Chen P, Boscia J, Heller B, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Kumar P, Adams AC, Van Naarden J, Custer KL, Durante M, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Kallewaard NL, Sabo J, Patel DR, Klekotka P, Shen L, Skovronsky DM. Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2021 Feb 16;325(7):632-644. doi: 10.1001/jama.2021.0202.

  PMID: 33475701 DERIVED

• Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM; BLAZE-1 Investigators. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):229-237. doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28.

  PMID: 33113295 DERIVED

Related Links

• A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1)

MeSH Terms

Conditions

COVID-19

Interventions

bamlanivimab; etesevimab; 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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Some treatment arms are open label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: June 17, 2020
• Primary Completion: February 21, 2023
• Study Completion: February 21, 2023
• Last Updated: April 11, 2024
• Results First Posted: March 7, 2022

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting
• Access Criteria: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting

Locations

US (12)