A Trial of GC4419 in Patients With Critical Illness Due to COVID-19

• Sponsor: Galera Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04555096
• Collaborator: (none)
• Enrollment: 16
• Locations: 3
• Arms: 2
• Actual Duration (Months): 8.6
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

A Trial of GC4419 in Patients with Critical Illness due to COVID-19

Condition or Disease	Intervention/Treatment	Phase
Covid19; SARS-CoV-2 Infection	Drug: GC4419; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot, Randomized, Placebo-Controlled Trial of GC4419 (Avasopasem Manganese) in Patients With Critical Illness Due to SARS-CoV-2 Infection (COVID-19)
• Actual Study Start Date: Sep 9, 2020
• Actual Primary Completion Date: May 28, 2021
• Actual Study Completion Date: May 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active GC4419 Arm A	Drug: GC4419; 180 Minute IV Infusion; Other Names: Avasopasem
Placebo Comparator: Placebo Arm B	Drug: Placebo; 180 Minute IV Infusion

Outcome Measures

Primary Outcome Measures

1. 28 Day All-cause Mortality [28 days]

   Death rate of patients with critical illness due to COVID-19 28 days after initiation of therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male or female subjects at least 18 years of age.

2. Ability to understand and the willingness to sign a written informed consent.

3. Laboratory-confirmed SARS-CoV-2 infection as determined by a positive PCR test documented prior to randomization

4. Requirement for intensive inpatient hospital care

5. Acute hypoxemic respiratory failure typifying ARDS

6. Adequate liver function

7. Use of effective contraception

Exclusion Criteria:

1. Expected survival for less than 48 hours after randomization

2. Child-Pugh stage C hepatic impairment and/or portal hypertension secondary to cirrhosis

3. Stage IV chronic kidney disease or end-stage kidney disease on maintenance hemodialysis

4. Requirement for extra-corporeal membrane oxygenation (ECMO)

5. Acute Myocardial Infarction (AMI)

6. Active bleeding requiring transfusion

7. Concurrent participation in another clinical trial of experimental treatment for SARSCoV-2

8. Female patients who are pregnant or breastfeeding

9. Requirement for concurrent treatment with nitrates

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa	Iowa City	Iowa	United States	52242
2	Saint Louis University	Saint Louis	Missouri	United States	63110
3	Mercy Research	Saint Louis	Missouri	United States	63141

Sponsors and Collaborators

• Galera Therapeutics, Inc.

Investigators

• Study Chair: Jon Holmlund, MD, Study Chair

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 8, 2021

More Information

Publications

None provided.

• Responsible Party: Galera Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04555096
• Other Study ID Numbers: COV-4419-201
• First Posted: Sep 18, 2020
• Last Update Posted: Mar 18, 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
• Keywords provided by Galera Therapeutics, Inc.: COVID19; SARS-CoV-2 Infection
• Additional relevant MeSH terms: Infections; COVID-19; Critical Illness; Avasopasem manganese

Study Results

Participant Flow

Arm/Group Title	Active GC4419	Placebo
Arm/Group Description	Arm A GC4419: 180 Minute IV Infusion	Arm B Placebo: 180 Minute IV Infusion
Period Title: Overall Study
STARTED	9	7
COMPLETED	4	2
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	Active GC4419	Placebo	Total
Arm/Group Description	Arm A GC4419: 180 Minute IV Infusion	Arm B Placebo: 180 Minute IV Infusion	Total of all reporting groups
Overall Participants	9	7	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.7 (6.89)	64.0 (11.28)	63.3 (61.5)
Sex: Female, Male (Count of Participants)
Female	1 11.1%	3 42.9%	4 25%
Male	8 88.9%	4 57.1%	12 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 22.2%	0 0%	2 12.5%
Not Hispanic or Latino	7 77.8%	7 100%	14 87.5%
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	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 22.2%	1 14.3%	3 18.8%
White	5 55.6%	5 71.4%	10 62.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 22.2%	1 14.3%	3 18.8%
Region of Enrollment (participants) [Number]
United States	9 100%	7 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	28 Day All-cause Mortality
Description	Death rate of patients with critical illness due to COVID-19 28 days after initiation of therapy.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active GC4419	Placebo
Arm/Group Description	Arm A GC4419: 180 Minute IV Infusion	Arm B Placebo: 180 Minute IV Infusion
Measure Participants	9	7
Alive	5 55.6%	3 42.9%
Death	4 44.4%	4 57.1%

Adverse Events

Time Frame	Adverse events collected from the baseline visit until 30 days after the last dose of GC4419/Placebo
Arm/Group Title	Active GC4419		Placebo
Arm/Group Description	Arm A GC4419: 180 Minute IV Infusion		Arm B Placebo: 180 Minute IV Infusion
All Cause Mortality
	Active GC4419		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)		4/7 (57.1%)
Serious Adverse Events
	Active GC4419		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		4/7 (57.1%)
Cardiac disorders
Cardiogenic Shock	1/9 (11.1%)	1	0/7 (0%)	0
Stress cardiomyopathy	1/9 (11.1%)	1	0/7 (0%)	0
Gastrointestinal disorders
Retroperitoneal haematoma	1/9 (11.1%)	1	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/9 (0%)	0	1/7 (14.3%)	1
Acute respiratory failure	2/9 (22.2%)	2	2/7 (28.6%)	2
Pneumothorax spontaneous	0/9 (0%)	0	1/7 (14.3%)	1
Respiratory arrest	1/9 (11.1%)	1	0/7 (0%)	0
Increased respiratory failure	0/9 (0%)	0	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Active GC4419		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)		7/7 (100%)
Blood and lymphatic system disorders
Anaemia of chronic disease	1/9 (11.1%)	1	0/7 (0%)	0
Blood loss anaemia	0/9 (0%)	0	1/7 (14.3%)	1
Leukocytosis	1/9 (11.1%)	1	0/7 (0%)	0
Cardiac disorders
Arteriospasm coronary	1/9 (11.1%)	1	0/7 (0%)	0
Atrial Fibrillation	1/9 (11.1%)	1	0/7 (0%)	0
Bradycardia	0/9 (0%)	0	1/7 (14.3%)	1
Cardiogenic Shock	1/9 (11.1%)	1	0/7 (0%)	0
Propofol infusion syndrome	1/9 (11.1%)	1	0/7 (0%)	0
Stress cardiomyopathy	1/9 (11.1%)	1	0/7 (0%)	0
Gastrointestinal disorders
Retroperitoneal haematoma	1/9 (11.1%)	1	0/7 (0%)	0
Constipation	1/9 (11.1%)	1	1/7 (14.3%)	1
Impaired gastric emptying	1/9 (11.1%)	1	0/7 (0%)	0
Lower gastrointestinal haemorrhage	0/9 (0%)	0	1/7 (14.3%)	1
Parotitis	1/9 (11.1%)	1	0/7 (0%)	0
General disorders
Decreased appetite	1/9 (11.1%)	1	0/7 (0%)	0
Pyrexia	3/9 (33.3%)	3	2/7 (28.6%)	2
Hypotension	5/9 (55.6%)	5	1/7 (14.3%)	1
Shock	0/9 (0%)	0	1/7 (14.3%)	1
Infections and infestations
Acute sinusitis	1/9 (11.1%)	1	0/7 (0%)	0
Bacteraemia	0/9 (0%)	0	1/7 (14.3%)	1
Pneumonia klebsiella	1/9 (11.1%)	1	0/7 (0%)	0
Septic shock	1/9 (11.1%)	1	0/7 (0%)	0
Urinary tract infection enterococcal	0/9 (0%)	0	1/7 (14.3%)	1
Viral upper respiratory tract infection	0/9 (0%)	0	1/7 (14.3%)	1
Investigations
Electrocardiogram QR prolonged	0/9 (0%)	0	1/7 (14.3%)	1
Electrocardiogram ST segment elevation	1/9 (11.1%)	1	0/7 (0%)	0
Metabolism and nutrition disorders
Hyperkalaemia	2/9 (22.2%)	2	0/7 (0%)	0
Hyperphosphataemia	2/9 (22.2%)	2	0/7 (0%)	0
Hypokalaemia	1/9 (11.1%)	1	2/7 (28.6%)	2
Hypophosphataemia	3/9 (33.3%)	3	0/7 (0%)	0
Malnutrition	1/9 (11.1%)	1	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/9 (11.1%)	1	0/7 (0%)	0
Psychiatric disorders
Anxiety	0/9 (0%)	0	1/7 (14.3%)	1
Hallucination	0/9 (0%)	0	1/7 (14.3%)	1
Renal and urinary disorders
Acute Kidney injury	2/9 (22.2%)	2	0/7 (0%)	0
Haematuria	0/9 (0%)	0	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/9 (0%)	0	1/7 (14.3%)	1
Acute respiratory failure	2/9 (22.2%)	2	2/7 (28.6%)	2
Hypoxia	3/9 (33.3%)	3	3/7 (42.9%)	3
Pneumothorax spontaneous	0/9 (0%)	0	1/7 (14.3%)	1
Respiratory arrest	1/9 (11.1%)	1	0/7 (0%)	0
Respiratory failure	0/9 (0%)	0	1/7 (14.3%)	1
Increase respiratory failure	0/9 (0%)	0	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/9 (11.1%)	1	0/7 (0%)	0
Rash erythematous	1/9 (11.1%)	1	0/7 (0%)	0
Skin injury	0/9 (0%)	0	1/7 (14.3%)	1
Vascular disorders
Distributive shock	1/9 (11.1%)	1	0/7 (0%)	0

Limitations/Caveats

Study was terminated early due to the inability to enroll critically ill COVID 19 patients as the height of the pandemic was over and the sites that were open for enrollment to the clinical study were no longer treating these types of patients.

More Information

Certain Agreements

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

There IS 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.