A Study of LY3127804 in Participants With COVID-19

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04342897
• Collaborator: (none)
• Enrollment: 95
• Locations: 13
• Arms: 2
• Actual Duration (Months): 5.7
• Patients Per Site: 7.3
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

A randomized, double-blind, placebo-controlled, clinical trial of LY3127804 in participants who are hospitalized with pneumonia and presumed or confirmed COVID-19.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; Pneumonia	Drug: LY3127804; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Clinical Trial of LY3127804 in Patients Who Are Hospitalized With Pneumonia and Presumed or Confirmed COVID-19
• Actual Study Start Date: Apr 20, 2020
• Actual Primary Completion Date: Oct 12, 2020
• Actual Study Completion Date: Oct 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY3127804 Participants received 20 milligrams (mg) per kilogram (kg) of LY3127804 as an intravenous (IV) infusion on Days 1 and 15.	Drug: LY3127804; Administered IV
Placebo Comparator: Placebo Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.	Drug: Placebo; Administered IV

Outcome Measures

Primary Outcome Measures

1. Ventilator Free Days [Day 1 through Day 28]

   Ventilator-free days were defined as the number of days from Day 1 through Day 28 on which a participant breathed without assistance, if the period of unassisted breathing lasted at least 24 consecutive hours and the participant did not die within 28 days from the first dose of the study drug.

Secondary Outcome Measures

1. Number of Participants Reported Lowest Score on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale [Day 1 through Day 28]

   The NIAID ordinal scale clinical status was defined as the lowest score achieved for that day, the lowest NIAID score from Day 1 through Day 28 for each participant was reported. NIAID ordinal assessment levels are reported by using the following 8 point scale, where a higher score is a better outcome: 1) death, 2) hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO), 3) hospitalized, on non-invasive ventilation or high-flow oxygen devices, 4) hospitalized, requiring supplemental oxygen, 5) hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19-related or otherwise), 6) hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care, 7) not hospitalized, limitation on activities and/or requiring home oxygen, and, 8) not hospitalized, no limitations on activities.

2. Percentage of Participants With Complete Response [Day 1 through Day 28]

   Complete response was defined as being alive and never requiring mechanical ventilator support (at any point while on study) through Day 28.

3. Number of Participants Who Died Between Day 1 Through Day 28 [Day 1 through Day 28]

4. Length of Hospitalization [Day 1 through Day 28]

   Days of participants hospitalization.

5. Number of Participants With Treatment-Emergent Serious Adverse Events (TE-SAE) [Day 1 through Day 60]

   An SAE is any AE from this study that results in one of the following outcomes: death that is not related to COVID-19 or a sequela of COVID-19 or death that is considered by the investigator to be related to study drug, prolonged inpatient hospitalization or re-hospitalization life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other SAE outcomes.

6. Number of Participants With Any Treatment Emergent Adverse Event (TEAE) [Day 1 through Day 60]

   TEAE was defined as any untoward medical occurrence that emerges during a defined treatment period, having been absent pre-treatment, or worsens relative to the pretreatment state, and does not necessarily had a causal relationship with the study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are hospitalized with pneumonia, and presumed or confirmed COVID-19

• Are able and willing to give signed informed consent (legally authorized representative can provide informed consent if needed)

Exclusion Criteria:

• Female participants must not be pregnant and/or lactating

• Have Acute Respiratory Distress Syndrome (ARDS) or will require immediate intermittent mandatory ventilation (IMV), or are ineligible for IMV

• Have any concurrent serious medical condition (for example dialysis) or concomitant medication that would preclude participation in the study

• Are moribund irrespective of the provision of treatments

• Have a known history or show evidence of human immunodeficiency virus (HIV) and/or hepatitis

• Have recently undergone major surgery or central venous access device placement

• Have a significant bleeding disorder or active vasculitis

• Have experienced a thromboembolic event

• Have symptomatic congestive heart failure, or symptomatic or poorly controlled cardiac arrhythmia

• Have a serious, nonhealing wound, peptic ulcer, or bone fracture

• Have liver cirrhosis

• Have a known sensitivity to monoclonal antibodies (mAbs) or other therapeutic proteins

• Have a history of hypertensive crisis or hypertensive encephalopathy or current, poorly controlled hypertension

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Univ Med Ctr Phoenix	Phoenix	Arizona	United States	85006
2	Banner Univ Med Ctr Tucson	Tucson	Arizona	United States	85719
3	National Jewish Medical and Research Center	Denver	Colorado	United States	80206
4	Nuvance Danbury Hospital	Danbury	Connecticut	United States	06810
5	NorthShore University HealthSystem	Evanston	Illinois	United States	60201
6	Parkview Research Center	Fort Wayne	Indiana	United States	46845
7	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
8	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
9	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
10	Henry Ford Hospital Detroit	Detroit	Michigan	United States	48202-2689
11	Allina Hospital Network	Minneapolis	Minnesota	United States	55404
12	State University of New York Hospital	Syracuse	New York	United States	13210
13	East Carolina University	Greenville	North Carolina	United States	27834

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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 Documents (Full-Text)

• Study Protocol - Jun 11, 2020
• Statistical Analysis Plan - Feb 9, 2021

More Information

Additional Information:

• A Study of LY3127804 in Participants With COVID-19

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04342897
• Other Study ID Numbers: 17824; I7W-MC-UDAA
• First Posted: Apr 13, 2020
• Last Update Posted: Aug 12, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: Corona Virus Disease 19 (COVID-19); 2019 Novel Coronavirus (2019 n-COV); Severe Acute Respiratory Syndrome (SARS); Pulmonary Disease; SARS-CoV-2
• Additional relevant MeSH terms: COVID-19; Pneumonia; Zansecimab

Study Results

Participant Flow

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 milligrams (mg) per kilogram (kg) of LY3127804 as an intravenous (IV) infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Period Title: Overall Study
STARTED	47	48
Received at Least One Dose of Study Drug	47	48
COMPLETED	33	36
NOT COMPLETED	14	12

Baseline Characteristics

Arm/Group Title	LY3127804	Placebo	Total
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.	Total of all reporting groups
Overall Participants	47	48	95
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.3 (14.13)	55.5 (14.40)	54.9 (14.20)
Sex: Female, Male (Count of Participants)
Female	18 38.3%	17 35.4%	35 36.8%
Male	29 61.7%	31 64.6%	60 63.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 48.9%	20 41.7%	43 45.3%
Not Hispanic or Latino	24 51.1%	28 58.3%	52 54.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 4.3%	2 4.2%	4 4.2%
Native Hawaiian or Other Pacific Islander	0 0%	1 2.1%	1 1.1%
Black or African American	8 17%	7 14.6%	15 15.8%
White	36 76.6%	38 79.2%	74 77.9%
More than one race	1 2.1%	0 0%	1 1.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	47 100%	48 100%	95 100%
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	33.74 (6.963)	33.70 (7.715)	33.72 (7.314)

Outcome Measures

1. Primary Outcome

Title	Ventilator Free Days
Description	Ventilator-free days were defined as the number of days from Day 1 through Day 28 on which a participant breathed without assistance, if the period of unassisted breathing lasted at least 24 consecutive hours and the participant did not die within 28 days from the first dose of the study drug.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
Median (Full Range) [days]	28	28

2. Secondary Outcome

Title	Number of Participants Reported Lowest Score on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale
Description	The NIAID ordinal scale clinical status was defined as the lowest score achieved for that day, the lowest NIAID score from Day 1 through Day 28 for each participant was reported. NIAID ordinal assessment levels are reported by using the following 8 point scale, where a higher score is a better outcome: 1) death, 2) hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO), 3) hospitalized, on non-invasive ventilation or high-flow oxygen devices, 4) hospitalized, requiring supplemental oxygen, 5) hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19-related or otherwise), 6) hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care, 7) not hospitalized, limitation on activities and/or requiring home oxygen, and, 8) not hospitalized, no limitations on activities.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
NIAID Level 1	7 14.9%	4 8.3%
NIAID Level 2	3 6.4%	2 4.2%
NIAID Level 3	12 25.5%	21 43.8%
NIAID Level 4	24 51.1%	19 39.6%
NIAID Level 5	1 2.1%	2 4.2%
NIAID Level 6	0 0%	0 0%
NIAID Level 7	0 0%	0 0%
NIAID Level 8	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Complete Response
Description	Complete response was defined as being alive and never requiring mechanical ventilator support (at any point while on study) through Day 28.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
Number [percentage of participants]	78.7 167.4%	87.5 182.3%

4. Secondary Outcome

Title	Number of Participants Who Died Between Day 1 Through Day 28
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
Number [participants]	7 14.9%	4 8.3%

5. Secondary Outcome

Title	Length of Hospitalization
Description	Days of participants hospitalization.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
Median (Inter-Quartile Range) [days]	6	6

6. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Serious Adverse Events (TE-SAE)
Description	An SAE is any AE from this study that results in one of the following outcomes: death that is not related to COVID-19 or a sequela of COVID-19 or death that is considered by the investigator to be related to study drug, prolonged inpatient hospitalization or re-hospitalization life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other SAE outcomes.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
Number [participants]	6 12.8%	2 4.2%

7. Secondary Outcome

Title	Number of Participants With Any Treatment Emergent Adverse Event (TEAE)
Description	TEAE was defined as any untoward medical occurrence that emerges during a defined treatment period, having been absent pre-treatment, or worsens relative to the pretreatment state, and does not necessarily had a causal relationship with the study treatment.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY3127804	Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.	Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
Measure Participants	47	48
Number [participants]	33 70.2%	31 64.6%

Adverse Events

Time Frame	Day 1 through Day 60
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug.
Arm/Group Title	LY3127804		Placebo
Arm/Group Description	Participants received 20 mg/kg of LY3127804 as an IV infusion on Days 1 and 15.		Participants received 20 mg/kg of Placebo as an IV infusion on Days 1 and 15.
All Cause Mortality
	LY3127804		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/47 (17%)		6/48 (12.5%)
Serious Adverse Events
	LY3127804		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/47 (12.8%)		2/48 (4.2%)
Cardiac disorders
Atrial fibrillation	2/47 (4.3%)	2	1/48 (2.1%)	1
Cardiac arrest	1/47 (2.1%)	1	0/48 (0%)	0
Gastrointestinal disorders
Duodenal ulcer	1/47 (2.1%)	1	0/48 (0%)	0
Intestinal ischaemia	1/47 (2.1%)	1	0/48 (0%)	0
Infections and infestations
Pneumonia	1/47 (2.1%)	1	0/48 (0%)	0
Pneumonia bacterial	1/47 (2.1%)	1	0/48 (0%)	0
Sepsis	1/47 (2.1%)	1	0/48 (0%)	0
Urinary tract infection	1/47 (2.1%)	1	0/48 (0%)	0
Injury, poisoning and procedural complications
Traumatic haemothorax	1/47 (2.1%)	1	0/48 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	1/47 (2.1%)	1	0/48 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/47 (0%)	0	1/48 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/47 (2.1%)	1	0/48 (0%)	0
Pneumothorax	1/47 (2.1%)	2	1/48 (2.1%)	1
Other (Not Including Serious) Adverse Events
	LY3127804		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/47 (63.8%)		31/48 (64.6%)
Blood and lymphatic system disorders
Leukocytosis	5/47 (10.6%)	5	1/48 (2.1%)	1
Gastrointestinal disorders
Constipation	6/47 (12.8%)	6	7/48 (14.6%)	7
Diarrhoea	3/47 (6.4%)	3	3/48 (6.3%)	3
Nausea	3/47 (6.4%)	3	1/48 (2.1%)	1
Infections and infestations
Oral candidiasis	3/47 (6.4%)	3	0/48 (0%)	0
Septic shock	3/47 (6.4%)	3	2/48 (4.2%)	2
Urinary tract infection	3/47 (6.4%)	3	2/48 (4.2%)	2
Metabolism and nutrition disorders
Hyperglycaemia	3/47 (6.4%)	3	3/48 (6.3%)	3
Hyperkalaemia	1/47 (2.1%)	1	3/48 (6.3%)	3
Hypokalaemia	5/47 (10.6%)	6	3/48 (6.3%)	3
Nervous system disorders
Encephalopathy	3/47 (6.4%)	3	2/48 (4.2%)	3
Psychiatric disorders
Anxiety	4/47 (8.5%)	4	6/48 (12.5%)	6
Insomnia	5/47 (10.6%)	5	3/48 (6.3%)	3
Renal and urinary disorders
Acute kidney injury	3/47 (6.4%)	3	4/48 (8.3%)	6
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	3/47 (6.4%)	3	1/48 (2.1%)	2
Dyspnoea	0/47 (0%)	0	3/48 (6.3%)	3
Hypoxia	3/47 (6.4%)	3	3/48 (6.3%)	3
Respiratory failure	4/47 (8.5%)	4	5/48 (10.4%)	5
Vascular disorders
Hypertension	4/47 (8.5%)	5	3/48 (6.3%)	3
Hypotension	3/47 (6.4%)	4	3/48 (6.3%)	4

Limitations/Caveats

The study was terminated for futility reason.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.