A Study of Immune System Proteins in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4)

Lilly

Status and phase: Completed; Phase 2

Conditions: COVID-19

Treatments: Drug: Placebo; Drug: Bebtelovimab; Drug: Etesevimab; Drug: Bamlanivimab; Drug: VIR-7831

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04634409

J2X-MC-PYAH (Other Identifier)

18160

Details and patient eligibility

About

The purpose of this study is to measure how well monoclonal antibodies work, either alone or in combination, against the virus that causes COVID-19. Study drug(s) 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 or 24 weeks and includes at least 1 visit to the study site, with the remainder of assessments performed in the home, local clinic, or by phone.

Enrollment: 1,755 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• For low-risk participant arms 9-11 only: Are greater than or equal to (≥)18 and less than (<)65 years of age at the time of randomization and do not have the risk factors defined in the bullet point directly below

• For high-risk participant arms 12 and 13 only:

  -- Are ≥18 years of age and satisfy at least one of the following risk factors at the time of screening

  • Are ≥65 years of age

  • Have a body mass index (BMI) ≥ 35

  • Have chronic kidney disease

  • Have type 1 or type 2 diabetes

  • Have immunosuppressive disease

  • Are currently receiving immunosuppressive treatment, or

  • Are ≥55 years of age AND have

    • cardiovascular disease, OR
    • hypertension, OR
    • chronic obstructive pulmonary disease or other chronic respiratory disease

• For high-risk participant arms 12 and 13 only:

  • Are 12-17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time of screening

    • Have a BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm
    • Have sickle cell disease
    • Have congenital or acquired heart disease
    • Have neurodevelopmental disorders, for example, cerebral palsy
    • Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
    • Have asthma or reactive airway or other chronic respiratory disease that requires daily medication for control
    • Have type 1 or type 2 diabetes
    • Have chronic kidney disease
    • Have immunosuppressive disease, or
    • Are currently receiving immunosuppressive treatment.

For high-risk participants arm 14 only:

• Are ≥12 years of age and satisfy at least one of the following risk factors at the time of screening Are ≥65 years of age
• Are adults (≥18 years of age) with BMI >25 kg/m2 , or if age 12-17, have BMI ≥85th percentile for their age and gender based on CDC growth charts
• Have chronic kidney disease
• Have type 1 or type 2 diabetes
• Have immunosuppressive disease
• Are currently receiving immunosuppressive treatment
• Have cardiovascular disease (including congenital heart disease) or hypertension
• Have chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
• Have sickle cell disease
• Have neurodevelopmental disorder (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
• Have a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID-19]
• Are currently not hospitalized
• 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, nasal congestion or runny nose, new loss of smell, chills
• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
• Are men or non-pregnant women who agree to contraceptive requirements
• Understand and agree to comply with planned study procedures
• Agree to the collection of nasopharyngeal swabs and venous blood
• The participant or legally authorized representative give signed informed consent and/or assent

Exclusion criteria

• For low-risk participants only: BMI ≥35
• 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) <300, respiratory rate ≥30 per minute, heart rate ≥125 per minute
• Require mechanical ventilation or anticipated impending need for mechanical ventilation
• 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 severe acute respiratory syndrome coronavirus 2 (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 a history of convalescent COVID-19 plasma treatment
• For low-risk arms only: have received a SARS-CoV-2 vaccine or have participated in a previous SARS-CoV-2 vaccine study and are currently blinded to treatment allotment
• 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
• Are pregnant or breast feeding
• Are investigator site personnel directly affiliated with this study
• Have body weight <40 kilograms

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,755 participants in 6 patient groups, including a placebo group

Placebo (Pbo)

Placebo Comparator group

Description:

Treatment 1: Pbo administered intravenously (IV). Treatment 8: Pbo For 700 mg Bamlanivimab (BAM) + 500 mg VIR-7831 (Amendment (C-e)) administered IV. Treatment 11: Pbo For 175 mg Bebtelovimab (BEB) \& 700 mg BAM +1400 mg Etesevimab ( ETE) +175 mg BEB (Low Risk Participants) administered IV. Pooled Placebo (Addendum 4, IV) administered IV. Pooled Placebo (Addendum 4, SC) administered SC.

Treatment:

Drug: Placebo

BAM + ETE

Experimental group

Description:

Treatment 2: 175 mg BAM +350 mg ETE administered IV. Treatment 3: 700 mg BAM +1400 mg ETE administered IV. Treatment 4: 2800 mg BAM +2800 mg ETE administered IV. Treatment 6: 350 mg BAM +700 mg ETE administered IV. Unintentional Dosing: 700 mg BAM +700 mg ETE administered IV. 700 mg BAM + 1400 mg ETE 30-min (Addendum (2)) administered IV. 700 mg BAM + 1400 mg ETE 15-min (Addendum (2)) administered IV.

Treatment:

Drug: Bamlanivimab

Drug: Etesevimab

BAM

Experimental group

Description:

Treatment 5: 700 mg BAM administered IV. 700 mg BAM 15-min (Addendum (2)) administered IV.

Treatment:

Drug: Bamlanivimab

BAM + VIR-7831

Experimental group

Description:

Treatment 7: 700 mg BAM + 500 mg VIR-7831 (Amendment (C-e)) administered IV.

Treatment:

Drug: VIR-7831

Drug: Bamlanivimab

BEB

Experimental group

Description:

Treatment 9: 175 mg BEB (Amendment (f), Low Risk Participants) administered IV. Treatment 12: 175 mg BEB (Amendment (f), High Risk Participants) administered IV. 70 mg BEB 140 mg/Min (Addendum 4, IV) administered IV. 175 mg BEB 140 mg/Min (Addendum 4, IV) administered IV. 175 mg BEB 350 mg/Min (Addendum 4, IV) administered IV. 1750 mg BEB 350 mg/Min (Addendum 4, IV) administered IV. 280 mg BEB (Addendum 4, SC) administered SC. 560 mg BEB (Addendum 4, SC) administered SC.

Treatment:

Drug: Bebtelovimab

BAM+ ETE + BEB

Experimental group

Description:

Treatment 10: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), Low Risk Participants) administered IV. Treatment 13: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), High Risk Participants) administered IV. Treatment 14: 700 mg BAM + 1400 mg ETE + 175 mg BEB(Amendment (g), High Risk, Updated Centers for Disease Control and Prevention (CDC) Criteria) administered IV. 175/700/1400 mg BAM + ETE + BEB 350 mg/Min (Addendum 4, IV) administered IV.

Treatment:

Drug: Bamlanivimab

Drug: Etesevimab

Drug: Bebtelovimab