NCT05164120

Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19

Completed Phase 2 Results posted Last updated 19 September 2024

What this trial tests

Phase 2 trial testing Belnacasan in COVID-19 in 40 participants. Completed in 11 October 2022.

Timeline

14 December 2021

Primary endpoint
18 July 2022

11 October 2022

Quick facts

Lead sponsor	MedStar Health
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	40
Start date	14 December 2021
Primary completion	18 July 2022
Estimated completion	11 October 2022
Sites	2 locations across United States

Drugs / interventions tested

• Belnacasan — full drug profile →
• Placebo

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

MedStar Health

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety and Tolerability of Belnacasan Primary · Through 60 days post enrollment

Number of adverse events and serious adverse events

Number of adverse events

Group	Value	95% CI
Interventional	11
Placebo	10

Number of serious adverse events

Group	Value	95% CI
Interventional	0
Placebo	0

Sustained Recovery and Resolution Rates of Common COVID-19 Symptoms Secondary · Baseline and Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization

Proportion of subjects in treatment group versus placebo group, respectively, who, per symptom questionnaire, rate stuffy or runny nose, sore throat, cough, low energy or tiredness, muscle or body ache, headache, chills or shivering, feeling hot or feverish, nausea, vomiting, diarrhea, shortness of breath at rest, shortness of breath with exertion, or impairment in sense of smell or taste as mild, moderate or severe.

Runny/stuffy nose at Baseline

Group	Value	95% CI
Interventional	14
Placebo	19

Runny/stuffy nose at Day 4

Group	Value	95% CI
Interventional	13
Placebo	13

Runny/stuffy nose at Day 7

Group	Value	95% CI
Interventional	17
Placebo	17

Runny/stuffy nose at Day 10

Group	Value	95% CI
Interventional	6
Placebo	4

Runny/stuffy nose at Day 14

Group	Value	95% CI
Interventional	12
Placebo	10

Runny/stuffy nose at Day 21

Group	Value	95% CI
Interventional	5
Placebo	3

Runny/stuffy nose at Day 28

Group	Value	95% CI
Interventional	5
Placebo	1

Runny/stuffy nose at Day 42

Group	Value	95% CI
Interventional	1
Placebo	0

Sustained Improvement of Global Impression Rates Secondary · Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization

Proportion of subjects in treatment group versus placebo group, respectively, who per symptom questionnaire have answered for two consecutive days: "YES" to "In the past 24 hours, have you returned to your usual health (before your COVID-19 illness)?"; "YES" to "In the past 24 hours, have you returned to your usual activities (before your COVID-19 illness)?"

Day 4 "Returned to usual health"

Group	Value	95% CI
Interventional	0
Placebo	0

Day 7 "Returned to usual health"

Group	Value	95% CI
Interventional	5
Placebo	5

Day 10 "Returned to usual health"

Group	Value	95% CI
Interventional	5
Placebo	6

Day 14 "Returned to usual health"

Group	Value	95% CI
Interventional	11
Placebo	12

Day 21 "Returned to usual health"

Group	Value	95% CI
Interventional	11
Placebo	16

Day 28 "Returned to usual health"

Group	Value	95% CI
Interventional	12
Placebo	12

Day 42 "Returned to usual health"

Group	Value	95% CI
Interventional	16
Placebo	16

Day 60 "Returned to usual health"

Group	Value	95% CI
Interventional	16
Placebo	15

Time to Sustained Recovery or Resolution of Common COVID-19 Symptoms Secondary · Over 60 days post randomization

Comparison in treatment group versus placebo group, respectively, of the number of days from randomization to the first day of achieving sustained recovery and resolution rates of common COVID-19 symptoms.

Group	Value	95% CI
Interventional	20.6	± 18.1
Placebo	15.4	± 7.8

Time to Sustained Improvement of Global Impression Secondary · Over 60 days post randomization

Comparison in treatment group versus placebo group, respectively, of the mean number of days from randomization to the first day of achieving sustained improvement of global impression rates.

Group	Value	95% CI
Interventional	10.5	± 1.5
Placebo	13.5	± 2.9

Rates of Fever Secondary · Days between enrollment and day 2 post randomization

Proportion of subjects in treatment group versus placebo group, respectively, who, per thermometer, experienced fever at any point between enrollment and day 2 post randomization.

Group	Value	95% CI
Interventional	1
Placebo	0

Oxygenation Levels Secondary · Over 60 days post randomization

Average change from baseline over 60 days in percentage of blood saturation

Group	Value	95% CI
Interventional	-0.01	-0.01 – 0.00
Placebo	-0.01	-0.02 – 0.01

Time in Days to Normalization of Fever and Oxygenation Levels. Secondary · 28 Days

Comparison in treatment group versus placebo group, respectively, of the number of days from randomization to the first day of achieving sustained (i.e., at least 2 days) resolution of fever for subjects who presented with fever at any point between enrollment and day 2 post randomization; with temperature \<38C or \>=38C experienced in total during the first 28 days post randomization; from randomization to the first day post randomization of achieving oxygenation of SpO2\>=96% in room air when resting for subjects who presented with SpO2\>93% and \<96% in room air, when resting, at enrollmen

Time in days to normalization of fever

Group	Value	95% CI
Interventional	4	± 0.00

Time in days to normalization of oxygenation level

Group	Value	95% CI
Placebo	7	± 0.00

Experiences of COVID-19 Related Deterioration and Mortality Secondary · Days 14, 28 and 60 post randomization

Proportion of treatment group, versus placebo group, respectively, who per subject reporting or medical records had experienced an emergency department visit, other than at study enrollment or study visits; hospitalization for COVID-19; hospitalization for COVID-19 requiring oxygen; hospitalization for COVID-19 requiring ICU; hospitalization for COVID-19 requiring ventilation; COVID-19 related death; death; hospitalization or death on Days 14, 28, and 60.

Subjects who had COVID-related: ER visit, hospitalization, ICU visit, or died by Day 14.

Group	Value	95% CI
Interventional	0
Placebo	0

Subjects who had COVID-related: ER visit, hospitalization, ICU visit, or died by Day 28

Group	Value	95% CI
Interventional	0
Placebo	0

Subjects who had COVID-related: ER visit, hospitalization, ICU visit, or died by Day 60

Group	Value	95% CI
Interventional	0
Placebo	0

Subjects who required oxygen or ventilation by Day 14

Group	Value	95% CI
Interventional	0
Placebo	0

Subjects who required oxygen or ventilation by Day 28

Group	Value	95% CI
Interventional	0
Placebo	0

Subjects who required oxygen or ventilation by Day 60

Group	Value	95% CI
Interventional	0
Placebo	0

The Number of Subjects With COVID-19 Related Deterioration and Mortality Experiences Secondary · Over 28 days

Comparison of treatment group versus placebo group, respectively, in the number of subjects who following randomization experienced hospitalization for COVID-19 related deterioration: requiring oxygen, requiring ICU admission, requiring ventilation.

Group	Value	95% CI
Interventional	0
Placebo	0

Changes on the WHO 9-Point Ordinal Scale Secondary · Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization

The counts of participants in the treatment group versus placebo group, respectively, who per questionnaire on WHO 9-point ordinal scale \[0: Uninfected or "no clinical or virological evidence of infection"; 1: Not hospitalized, no limitations on activities; 2: Not hospitalized, limitation on activities; 3: Hospitalized, not requiring supplemental oxygen; 4: Hospitalized, requiring supplemental oxygen; 5: Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6: Hospitalized, intubated; 7: Hospitalized, advanced life support including invasive mechanical ventilation or ECMO; 8:

Day 4

Group	Value	95% CI
Interventional	3
Placebo	6

Day 7

Group	Value	95% CI
Interventional	8
Placebo	8

Day 10

Group	Value	95% CI
Interventional	14
Placebo	13

Day 14

Group	Value	95% CI
Interventional	14
Placebo	11

Day 21

Group	Value	95% CI
Interventional	15
Placebo	15

Day 28

Group	Value	95% CI
Interventional	16
Placebo	16

Day 42

Group	Value	95% CI
Interventional	16
Placebo	16

Day 60

Group	Value	95% CI
Interventional	17
Placebo	15

Values on the WHO 9-Point Ordinal Scale Secondary · Days 14, 28, and 60 post randomization

Comparison of treatment group versus placebo group, respectively, in the average of daily scale value (0-8) on Days 14, 28, and 60 with respect to the number of subjects who reported as uninfected (scale value of 0), had no limitations (scale value of 1), or were experiencing limitations (scale value of 2). All patients had a score ranging between 0-2. A description of the WHO 9-Point Ordinal Scale follows: 0\. Uninfected or "no clinical or virological evidence of infection" * defined as subject answering "Yes" to "In the past 24 hours, have you returned to your usual health (before your CO

Average WHO-9 point scale value at Day 14

Group	Value	95% CI
Interventional	1.00	± 0.69
Placebo	0.94	± 0.87

Average WHO-9 point scale value at Day 28

Group	Value	95% CI
Interventional	0.33	± 0.69
Placebo	0.17	± 0.51

Average WHO-9 point scale value at Day 60

Group	Value	95% CI
Interventional	0.00	± 0.00
Placebo	0.12	± 0.48

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of enrollment through Day 60. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Interventional

Serious: 0/20 (0%)

Deaths: 0/20

Placebo

Serious: 0/20 (0%)

Deaths: 0/20

Other adverse events (1 terms — click to expand)

Reaction	System	Interventional	Placebo
Chest pain	Cardiac disorders	—	—

Data from ClinicalTrials.gov NCT05164120 adverse events section.

Sponsor's own description

The purpose of this trial is to assess the safety, tolerability and treatment effect of the orally administered Caspase-1 inhibitor, belnacasan, for the treatment of patients with mild to moderate COVID-19 and to generate proof of concept for future trials.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Reframing the link between metabolism and NLRP3 inflammasome: therapeutic opportunities.
   Ortega MA, De Leon-Oliva D, García-Montero C, Fraile-Martinez O, et al · · 2023 · cited 28× · PMID 37545507 · DOI 10.3389/fimmu.2023.1232629
2. Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.
   Ago Y, Rintz E, Musini KS, Ma Z, et al · · 2024 · cited 18× · PMID 38256186 · DOI 10.3390/ijms25021113
3. The roles of cellular protease interactions in viral infections and programmed cell death: a lesson learned from the SARS-CoV-2 outbreak and COVID-19 pandemic.
   Majchrzak M, Poręba M. · · 2022 · cited 13× · PMID 35997950 · DOI 10.1007/s43440-022-00394-9
4. Evidence of Failed Resolution Mechanisms in Arrhythmogenic Inflammation, Fibrosis and Right Heart Disease.
   Younes R, LeBlanc CA, Hiram R. · · 2022 · cited 10× · PMID 35625647 · DOI 10.3390/biom12050720
5. Macrophage pyroptosis mediates hyperoxia-induced inflammatory lung injury in neonates.
   Tu Z, Guo H, Gao Y, Xiao W, et al · · 2025 · cited 4× · PMID 40486518 · DOI 10.3389/fimmu.2025.1546986
6. The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.
   Zou C, Jiang S, Li H, Zhao K, et al · · 2026 · PMID 41799937 · DOI 10.1002/mco2.70660