Safety and Efficacy of NP-120 (Ifenprodil) for the Treatment of Hospitalized Patient With Confirmed COVID-19 Disease

• ClinicalTrials.gov Identifier: NCT04382924
• Recruitment Status: Completed
• First Posted: May 11, 2020
• Results First Posted: December 3, 2021
• Last Update Posted: December 3, 2021
• Sponsor: Algernon Pharmaceuticals
• Collaborator: Novotech (Australia)
• Information provided by (Responsible Party): Algernon Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID
• Intervention: Drug: NP-120 (Ifenprodil)
• Enrollment: 168

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Period Title: Overall Study
Started	52	56	60
Completed	44	46	48
Not Completed	8	10	12
Reason Not Completed
Death	2	5	4
Protocol Violation	0	1	1
Transferred to other hospital/declined in person visits	0	1	1
Withdrawal by Subject	6	3	6

Baseline Characteristics

Arm/Group Title		Treatment Arm A	Treatment Arm B	Control Arm	Total
Arm/Group Description		NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only	Total of all reporting groups
Overall Number of Baseline Participants		52	56	60	168
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	52 participants	56 participants	60 participants	168 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	38 73.1%	36 64.3%	36 60.0%	110 65.5%
	>=65 years	14 26.9%	20 35.7%	24 40.0%	58 34.5%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	52 participants	56 participants	60 participants	168 participants
		56.1 (13.1)	58.5 (14.5)	59.7 (12.9)	58.2 (13.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	52 participants	56 participants	60 participants	168 participants
	Female	20 38.5%	27 48.2%	21 35.0%	68 40.5%
	Male	32 61.5%	29 51.8%	39 65.0%	100 59.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	52 participants	56 participants	60 participants	168 participants
	Hispanic or Latino	2 3.8%	4 7.1%	7 11.7%	13 7.7%
	Not Hispanic or Latino	49 94.2%	52 92.9%	53 88.3%	154 91.7%
	Unknown or Not Reported	1 1.9%	0 0.0%	0 0.0%	1 0.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	52 participants	56 participants	60 participants	168 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	16 30.8%	18 32.1%	18 30.0%	52 31.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 1.9%	1 1.8%	0 0.0%	2 1.2%
	White	35 67.3%	35 62.5%	41 68.3%	111 66.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	2 3.6%	1 1.7%	3 1.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	52 participants	56 participants	60 participants	168 participants
Romania		29	29	30	88
United States		7	10	12	29
Philippines		15	17	18	50
Australia		1	0	0	1
Patient clinical status on WHO 7 point ordinal scale; Mean (Standard Deviation); Unit of measure: Scores on a scale
	Number Analyzed	52 participants	56 participants	60 participants	168 participants
		4.23 (0.425)	4.25 (0.548)	4.25 (0.437)	4.24 (0.471)

Outcome Measures

1. Primary Outcome

Title	Patient Clinical Status (on the WHO 7-point Ordinal Scale) at Day 15 in IP Versus SOC Control Group Patients:
Description	Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Analysis performed on the number of patients with WHO-7 data

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	46	44	48
Measure Type: Count of Participants; Unit of Measure: Participants
1. Not hospitalized no limitations on activities	10 21.7%	9 20.5%	18 37.5%
2. Not hospitalized but limitations on activities	7 15.2%	9 20.5%	2 4.2%
3. Hospitalized not requiring supplemental O2	13 28.3%	13 29.5%	16 33.3%
4. Hospitalized and requires supplemental O2	13 28.3%	8 18.2%	7 14.6%
5. Hospitalized and on non-invasive ventilation or high flow O2	1 2.2%	1 2.3%	1 2.1%
6. Hospitalized and on mechanical ventilation or ECMO	2 4.3%	1 2.3%	2 4.2%
7. Death	0 0.0%	3 6.8%	2 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm A, Treatment Arm B, Control Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.025
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	0.0001
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Status on an Ordinal Scale Assessed Daily While Hospitalized and on Days 15 and 28 in IP Versus Control Group Patients
Description	WHO status of subjects at timepoints from baseline to day 28; Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death
Time Frame	Days 1 through 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	52	56	60
Mean (Standard Deviation); Unit of Measure: scores on a scale
Baseline	4.23 (0.425)	4.25 (0.548)	4.25 (0.427)
Day 3	4.22 (0.503)	4.22 (0.718)	4.29 (0.7063)
Day 5	4.12 (0.627)	4.14 (0.917)	4.18 (0.819)
Day 8	3.89 (0.767)	4.02 (1.012)	4.04 (0.988)
Day 11	3.87 (0.777)	4.09 (1.156)	3.97 (1.098)
Day 15	2.87 (1.343)	2.95 (1.628)	2.96 (1.665)
Day 28	1.59 (1.384)	1.80 (1.608)	1.73 (1.730)

3. Secondary Outcome

Title	NEWS Assessed Days 3, 5, 8 ,11 Daily While Hospitalized and on Days 15 and 29 in IP Versus Control Group Patients
Description	National Early Warning Score assessed between baseline and Day 29 on subjects in 20, 40 mg TID NP-120 arms versus control group The National Early Warning Score (NEWS) scale is a composite of 7 physiological parameters: Respiration Rate (per minute),Oxygen Saturations (%), Any Supplemental Oxygen, Temperature (°C), Systolic BP (mmHg), Heart Rate (per minute), Level of Consciousness. The aggregate results from all 7 physiological parameters are used to obtain the NEW Score., ranging from 0 - 20. Higher values reflect a worse outcome.
Time Frame	Days 3, 5, 8, 11, 25, 29

Outcome Measure Data

Analysis Population Description

NEWS score collected on patients currently hospitalized, or returning for follow up visits

Arm/Group Title		Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:		NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed		52	56	60
Mean (Standard Deviation); Unit of Measure: scores on a scale
Baseline	Number Analyzed	52 participants	56 participants	60 participants
		4.7 (1.83)	4.5 (1.58)	4.5 (1.51)
Day 3	Number Analyzed	51 participants	53 participants	55 participants
		4.2 (1.90)	3.7 (1.60)	4.4 (1.91)
Day 5	Number Analyzed	50 participants	49 participants	54 participants
		3.8 (2.04)	3.3 (1.95)	3.7 (1.99)
Day 8	Number Analyzed	46 participants	40 participants	45 participants
		3.5 (2.33)	3.1 (2.04)	3.0 (2.51)
Day 11	Number Analyzed	38 participants	30 participants	34 participants
		3.0 (2.21)	3.0 (2.60)	3.2 (2.39)
Day 15	Number Analyzed	46 participants	39 participants	44 participants
		2.4 (2.85)	1.8 (2.38)	1.8 (2.37)
Day 29	Number Analyzed	36 participants	39 participants	40 participants
		1.1 (1.97)	1.4 (2.10)	1.3 (2.11)

4. Secondary Outcome

Title	Rate of Mechanical Ventilation in IP Versus Control Group Patients
Description	Rate of mechanical ventilation in 20 and 40 mg TID NP-120 versus control group
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	52	56	60
Measure Type: Count of Participants; Unit of Measure: Participants
	5 9.6%	2 3.6%	4 6.7%

5. Secondary Outcome

Title	Duration of Mechanical Ventilation (if Applicable) in IP Versus Control Group Patients
Description	Duration of mechanical ventilation in 20 and 40 mg TID subjects versus control who experience mechanical ventilation
Time Frame	Up to day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	5	2	4
Measure Type: Number; Unit of Measure: participants
< 6 hours	0	1	0
>= 12 hours but < 24 hours	0	0	0
>= 24 hours but <72 hours	1	0	0
>=72 hours but <120 hours	0	1	1
>= 120 hours	3	0	2
Ongoing at time of EOS (>= 24 hours but <72 hours	1	0	1

6. Secondary Outcome

Title	Duration of Supplemental Oxygen in IP Versus Control Group Patients
Description	Duration in patients only receiving supplemental oxygen in IP versus control group up to Day 29
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	46	48	52
Measure Type: Count of Participants; Unit of Measure: Participants
< 6 hours	0 0.0%	0 0.0%	0 0.0%
>= 12 hours but < 24 hours	0 0.0%	1 2.1%	0 0.0%
>= 24 hours but < 72 hours	4 8.7%	4 8.3%	5 9.6%
>= 72 hours but < 120 hours	7 15.2%	5 10.4%	8 15.4%
>= 120 hours	35 76.1%	38 79.2%	39 75.0%

7. Secondary Outcome

Title	Time to Return to Room Pressure (SpO2 > 94%) on Room Air
Description	Time to return to room pressure (SpO2 > 94%) on room air in patients in 20, 40 mg TID NP-120 groups versus control group with 94% blood oxygen levels at enrolment Time-to-event endpoints with competing risk were analysed for each dosing group using the Cumulative Incidence Function-CIF (KM) graphical display. Data represents the time (in Days) it took for all participants in the group to return to room pressure air (e.g. the time when the CIF curve hit 100%).
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	11	11	13
Measure Type: Number; Unit of Measure: Days
	4	5	9

8. Secondary Outcome

Title	Duration in ICU (if Applicable) in IP Versus Control Group Patients
Description	Duration of subject in ICU in 20 and 40 TID mg groups versus control group patients
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	8	6	9
Measure Type: Count of Participants; Unit of Measure: Participants
>= 1 day but < 3 days	0 0.0%	0 0.0%	0 0.0%
>= 3 days but < 7 days	1 12.5%	0 0.0%	1 11.1%
>=7 days but < 14 days	3 37.5%	3 50.0%	3 33.3%
>=14 days but < 21 days	1 12.5%	1 16.7%	2 22.2%
>= 21 days	2 25.0%	2 33.3%	2 22.2%
Ongoing at end of study	1 12.5%	0 0.0%	1 11.1%

9. Secondary Outcome

Title	Rate of Mortality in IP Versus Control Group Patients
Description	Rate of Overall Mortality in 20, 40 mg TID groups versus control group
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm A	Treatment Arm B	Control Arm
Arm/Group Description:	NP-120 (Ifenprodil) 20 mg TID + Standard of Care	NP-120 (Ifenprodil) 40 mg TID + Standard of Care	Standard of Care only
Overall Number of Participants Analyzed	52	56	60
Measure Type: Count of Participants; Unit of Measure: Participants
	2 3.8%	5 8.9%	4 6.7%

10. Secondary Outcome

Title	Duration of Hospitalization in IP Versus Control Group Patients
Description	[Not Specified]
Time Frame	Day 15, 28

Outcome Measure Data Not Reported

11. Secondary Outcome

Title	Time to Discharge in IP Versus Control Group Patients
Description	[Not Specified]
Time Frame	Day 15, 28

Outcome Measure Data Not Reported

12. Secondary Outcome

Title	Effect on the Rate of Change of Partial Pressure of Oxygen (PaO2) and PaO2/FiO2 Ratio Taken at Baseline and Measured Once Daily up to 2 Weeks of Treatment in IP Versus Control Group Patients
Description	[Not Specified]
Time Frame	Up to day 15, day 28

Outcome Measure Data Not Reported

Adverse Events

Time Frame	From Day 1 to Day 60
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment Arm A		Treatment Arm B		Control Arm
Arm/Group Description	NP-120 (Ifenprodil) 20 mg TID + Standard of Care		NP-120 (Ifenprodil) 40 mg TID + Standard of Care		Standard of Care only
All-Cause Mortality
	Treatment Arm A		Treatment Arm B		Control Arm
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	2/52 (3.85%)		5/56 (8.93%)		4/60 (6.67%)
Serious Adverse Events
	Treatment Arm A		Treatment Arm B		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/52 (3.85%)		6/56 (10.71%)		5/60 (8.33%)
Cardiac disorders
Cardiac Arrest † 1	2/52 (3.85%)	2	1/56 (1.79%)	1	2/60 (3.33%)	2
Cardiopulmonary Failure † 1	0/52 (0.00%)	0	0/56 (0.00%)	0	2/60 (3.33%)	2
Acute myocardial infarction † 1	0/52 (0.00%)	0	0/56 (0.00%)	0	1/60 (1.67%)	1
Coronary artery disease † 1	0/52 (0.00%)	0	1/56 (1.79%)	1	0/60 (0.00%)	0
Infections and infestations
COVID-19 pneumonia † 1	0/52 (0.00%)	0	1/56 (1.79%)	1	1/60 (1.67%)	1
Investigations
Coagulation test abnormal † 1	0/52 (0.00%)	0	1/56 (1.79%)	1	0/60 (0.00%)	0
Nervous system disorders
Seizure † 1	0/52 (0.00%)	0	1/56 (1.79%)	1	0/60 (0.00%)	0
Renal and urinary disorders
Pyelonephritis acute † 1	0/52 (0.00%)	0	1/56 (1.79%)	1	0/60 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	0/52 (0.00%)	0	1/56 (1.79%)	1	0/60 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment Arm A		Treatment Arm B		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/52 (69.23%)		35/56 (62.50%)		30/60 (50.00%)
Blood and lymphatic system disorders
Coagulopathy † 1	0/52 (0.00%)	0	4/56 (7.14%)	4	3/60 (5.00%)	3
Gastrointestinal disorders
Constipation † 1	2/52 (3.85%)	2	3/56 (5.36%)	3	3/60 (5.00%)	3
Diarrhoea † 1	3/52 (5.77%)	3	1/56 (1.79%)	1	3/60 (5.00%)	3
Flatulence † 1	1/52 (1.92%)	1	3/56 (5.36%)	3	1/60 (1.67%)	1
Nausea † 1	3/52 (5.77%)	3	0/56 (0.00%)	0	0/60 (0.00%)	0
Hepatobiliary disorders
Hepatocellular injury † 1	4/52 (7.69%)	5	5/56 (8.93%)	5	8/60 (13.33%)	8
Infections and infestations
Oral candidiasis † 1	6/52 (11.54%)	6	3/56 (5.36%)	3	1/60 (1.67%)	1
Urinary tract infection † 1	0/52 (0.00%)	0	3/56 (5.36%)	3	0/60 (0.00%)	0
Injury, poisoning and procedural complications
Vessel puncture site bruise † 1	3/52 (5.77%)	4	0/56 (0.00%)	0	1/60 (1.67%)	1
Metabolism and nutrition disorders
Hyperglycaemia † 1	5/52 (9.62%)	5	3/56 (5.36%)	3	1/60 (1.67%)	1
Hypoalbuminaemia † 1	3/52 (5.77%)	3	2/56 (3.57%)	2	4/60 (6.67%)	4
Psychiatric disorders
Anxiety † 1	1/52 (1.92%)	1	5/56 (8.93%)	5	2/60 (3.33%)	2
Insomnia † 1	2/52 (3.85%)	2	3/56 (5.36%)	3	3/60 (5.00%)	3
Skin and subcutaneous tissue disorders
Intertrigo † 1	3/52 (5.77%)	3	0/56 (0.00%)	0	0/60 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

• Name/Title: Dr. Christopher Bryan
• Organization: Algernon Pharmaceuticals
• Phone: 2045572308
• EMail: cbryan@algernonpharmaceuticals.com

• Responsible Party: Algernon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04382924
• Other Study ID Numbers: AGN120-3
• First Submitted: May 8, 2020
• First Posted: May 11, 2020
• Results First Submitted: November 22, 2021
• Results First Posted: December 3, 2021
• Last Update Posted: December 3, 2021