Clinical Trial to Evaluate CERC-002 in Adults With COVID-19 Pneumonia and Acute Lung Injury

• Sponsor: Aevi Genomic Medicine, LLC, a Cerecor company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04412057
• Collaborator: (none)
• Enrollment: 88
• Locations: 11
• Arms: 2
• Actual Duration (Months): 6.1
• Patients Per Site: 8
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The study is a prospective, randomized, placebo-controlled, double-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes), for the treatment of patients with 2019 novel coronavirus disease (COVID-19) pneumonia who have mild to moderate Acute Respiratory Distress Syndrome (ARDS).

LIGHT is a cytokine in the tumor necrosis factor super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS.

The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Pneumonia; Acute Lung Injury; ARDS	Drug: CERC-002; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double-blind (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID-19 Pneumonia and Acute Lung Injury
• Actual Study Start Date: Jul 17, 2020
• Actual Primary Completion Date: Dec 14, 2020
• Actual Study Completion Date: Jan 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CERC-002	Drug: CERC-002; Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.; Other Names: AEVI-002 and MDGN-002
Placebo Comparator: Placebo	Drug: Placebo; Administered once subcutaneously

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Alive and Free of Respiratory Failure [Baseline to Day 28]

   Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation

Secondary Outcome Measures

1. Number of Subjects Who Are Alive at Day 28 [Baseline to Day 28]

   1-month mortality defined as the number of subjects who are alive at the Day 28/ET visit

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Subject/legally authorized representative (LAR) is able to understand and provide written informed consent, and assent (as applicable) to participate in this study.

2. Subject is ≥18 years of age at the time of informed consent and assent (as applicable).

3. Subject is male or non-pregnant, non-lactating female, who if of childbearing potential agrees to comply with any applicable contraceptive requirements if. discharged from the hospital prior to completing the study.

4. Subject has a diagnosis of COVID-19 infection through an approved testing method.

5. Subject has been hospitalized due to clinical diagnosis of pneumonia with acute lung injury defined as diffuse bilateral radiographic infiltrates with partial pressure of arterial oxygen/percentage of inspired oxygen (PaO2/FiO2) >100 and <300.

6. Subject's oxygen saturation at rest in ambient air <93%

Exclusion Criteria:

1. Subject is intubated.

2. Subject is currently taking immunomodulators or anti-rejection drugs.

3. Subject has been administered an immunomodulating biologic drug within 60 days of baseline.

4. Subject is in septic shock defined as persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation.

5. Subject has received any live attenuated vaccine, such as varicella-zoster, oral polio, or rubella, within 3 months prior to the baseline visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hoag Memorial Hospital	Newport Beach	California	United States	92663
2	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982
3	Triple O Research Institute, P.A.	West Palm Beach	Florida	United States	33407
4	Parkview Research Center	Fort Wayne	Indiana	United States	46845
5	MedPharmics, LLC	Metairie	Louisiana	United States	70006
6	LSUHSC - Shreveport	Shreveport	Louisiana	United States	71103
7	Carolina Institute for Clinical Research, LLC	Fayetteville	North Carolina	United States	28304
8	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
9	AnMed Health Medical Center	Anderson	South Carolina	United States	29621
10	Lowcountry Infectious Diseases, P.A.	Charleston	South Carolina	United States	29414
11	BRCR Global Texas	McAllen	Texas	United States	78503

Sponsors and Collaborators

• Aevi Genomic Medicine, LLC, a Cerecor company

Investigators

• Study Director: Scott White, MD, Aevi Genomic Medicine, LLC, a Cerecor company

Study Documents (Full-Text)

• Study Protocol - Aug 12, 2020
• Statistical Analysis Plan - Dec 15, 2020

More Information

Publications

None provided.

• Responsible Party: Aevi Genomic Medicine, LLC, a Cerecor company
• ClinicalTrials.gov Identifier: NCT04412057
• Other Study ID Numbers: CERC-002-CVID-201
• First Posted: Jun 2, 2020
• Last Update Posted: Mar 24, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Pneumonia; Lung Injury; Acute Lung Injury; Wounds and Injuries

Study Results

Participant Flow

Recruitment Details	Of the 88 enrolled patients, 83 met inclusion criteria and were randomized to treatment.

Arm/Group Title	CERC-002	Placebo
Arm/Group Description	CERC-002: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.	Placebo: Administered once subcutaneously
Period Title: Overall Study
STARTED	41	42
Randomized Analysis Set	41	42
Safety Analysis Set	40	42
Full Analysis Set	40	42
Primary Analysis Set	31	31
COMPLETED	37	35
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	CERC-002	Placebo	Total
Arm/Group Description	CERC-002: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.	Placebo: Administered once subcutaneously	Total of all reporting groups
Overall Participants	41	42	83
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 58.5%	31 73.8%	55 66.3%
>=65 years	17 41.5%	11 26.2%	28 33.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (14.5)	58.1 (14.21)	58.7 (14.28)
Sex: Female, Male (Count of Participants)
Female	16 39%	10 23.8%	26 31.3%
Male	25 61%	32 76.2%	57 68.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 22%	10 23.8%	19 22.9%
Not Hispanic or Latino	32 78%	31 73.8%	63 75.9%
Unknown or Not Reported	0 0%	1 2.4%	1 1.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2.4%	1 1.2%
Asian	2 4.9%	0 0%	2 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 17.1%	3 7.1%	10 12%
White	31 75.6%	37 88.1%	68 81.9%
More than one race	1 2.4%	0 0%	1 1.2%
Unknown or Not Reported	0 0%	1 2.4%	1 1.2%
Region of Enrollment (Count of Participants)
United States	41 100%	42 100%	83 100%
Corticosteroid Use (Count of Participants)
Yes	37 90.2%	36 85.7%	73 88%
No	4 9.8%	6 14.3%	10 12%
Remdesivir Use (Count of Participants)
Yes	21 51.2%	27 64.3%	48 57.8%
No	20 48.8%	15 35.7%	35 42.2%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.3 (8.58)	32.3 (6.46)	33.3 (7.63)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Alive and Free of Respiratory Failure
Description	Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation
Time Frame	Baseline to Day 28

Outcome Measure Data

Analysis Population Description

The number of subjects alive and free of respiratory failure up to Day 28/Early Termination (ET). The study was designed with broad eligibility criteria allowing patients who received high-flow oxygen or positive-pressure oxygen prior to dosing to be enrolled. As overlap was expected patients who were in respiratory failure before dosing or who required elevation in their ventilation support were excluded from the primary analysis (N=20, 9 CERC-002 patients and 11 placebo patients).

Arm/Group Title	CERC-002	Placebo
Arm/Group Description	CERC-002: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.	Placebo: Administered once subcutaneously
Measure Participants	31	31
Count of Participants [Participants]	26 63.4%	20 47.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CERC-002, Placebo
	Comments	The sample size provided greater than 80% power to detect a difference of 0.25 in the proportion of subjects alive and free of respiratory failure using a Chi-square exact test at a one-sided significance level of 0.05. This calculation assumed that the proportion alive and free of respiratory failure will be 0.60 in the placebo group and 0.85 in the CERC-002 group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0440
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.86
	Confidence Interval	(2-Sided) 90%; 1.04 to 7.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Subjects Who Are Alive at Day 28
Description	1-month mortality defined as the number of subjects who are alive at the Day 28/ET visit
Time Frame	Baseline to Day 28

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all subjects who received at least one dose of investigational product and had a baseline and at least one post-baseline efficacy assessment. There was 1 subject who did not have a survival status at Day 28 so is therefore excluded from the secondary analysis of the number of subjects who were alive at Day 28.

Arm/Group Title	CERC-002	Placebo
Arm/Group Description	CERC-002: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.	Placebo: Administered once subcutaneously
Measure Participants	39	42
Count of Participants [Participants]	36 87.8%	36 85.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CERC-002, Placebo
	Comments	The proportion of subjects alive at Day 28/ET in the CERC-002 group was compared to that in the placebo group using logistic regression methods. The logistic regression model included terms for treatment group. Model based point estimate (i.e., odds ratio [OR]), 90% confidence interval [CI], and one-sided p-value were reported.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1762
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 90%; 0.59 to 6.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All adverse events were collected from the time of the informed consent until the end of study (Day 60). Therefore all serious and non-serious events are included regardless of meeting or not meeting the study definition of treatment emergent (eg, pre-treatment events are included).
Arm/Group Title	CERC-002		Placebo
Arm/Group Description	CERC-002: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.		Placebo: Administered once subcutaneously
All Cause Mortality
	CERC-002		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/40 (10%)		9/42 (21.4%)
Serious Adverse Events
	CERC-002		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/40 (20%)		12/42 (28.6%)
Cardiac disorders
Acute myocardial infarction	1/40 (2.5%)	1	0/42 (0%)	0
Cardiac arrest	2/40 (5%)	3	2/42 (4.8%)	2
Ventricular Fibrillation	1/40 (2.5%)	1	1/42 (2.4%)	1
Bradycardia	0/40 (0%)	0	1/42 (2.4%)	1
Pulseless electrical activity	0/40 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/40 (0%)	0	1/42 (2.4%)	1
General disorders
Non-cardiac chest pain	1/40 (2.5%)	1	0/42 (0%)	0
Adverse event	0/40 (0%)	0	1/42 (2.4%)	1
Infections and infestations
Sepsis	1/40 (2.5%)	1	0/42 (0%)	0
Urinary tract infection	1/40 (2.5%)	1	0/42 (0%)	0
COVID-19 pneumonia	0/40 (0%)	0	2/42 (4.8%)	2
Septic shock	0/40 (0%)	0	2/42 (4.8%)	2
Nervous system disorders
Cerebral infarction	1/40 (2.5%)	1	0/42 (0%)	0
Renal and urinary disorders
Renal failure	1/40 (2.5%)	1	0/42 (0%)	0
Acute kidney injury	0/40 (0%)	0	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/40 (2.5%)	1	2/42 (4.8%)	3
Pneumomediastinum	1/40 (2.5%)	1	0/42 (0%)	0
Pneumothorax	1/40 (2.5%)	1	0/42 (0%)	0
Acute respiratory distress syndrome	0/40 (0%)	0	2/42 (4.8%)	2
Epistaxis	0/40 (0%)	0	1/42 (2.4%)	1
Respiratory failure	3/40 (7.5%)	3	5/42 (11.9%)	6
Vascular disorders
Hypotension	1/40 (2.5%)	1	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	CERC-002		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/40 (25%)		6/42 (14.3%)
Blood and lymphatic system disorders
Anaemia	4/40 (10%)	7	3/42 (7.1%)	3
Leukocytosis	6/40 (15%)	8	4/42 (9.5%)	4
Investigations
Hepatic Enzyme Increased	4/40 (10%)	5	2/42 (4.8%)	2
Renal and urinary disorders
Acute Kidney Injury	3/40 (7.5%)	3	1/42 (2.4%)	1

Limitations/Caveats

The study was designed to use broad eligibility criteria including patients who received high-flow oxygen or positive-pressure oxygen prior to randomization. Some overlap was expected between the entry criteria and the primary endpoint. Therefore patients who were in respiratory failure before dosing or who required an elevation in their ventilation support were excluded (N=20). In addition, to increase statistical power, a 1-sided χ2 test was used.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.