Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19
- Registration Number
- NCT05164120
- Lead Sponsor
- MedStar Health
- Brief Summary
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.
- Detailed Description
COVID-19 is an acute respiratory disease caused by the SARS-CoV-2 virus which has impacted the lives of millions of patients. Though vaccines and preventive treatments such as monoclonal antibodies, steroids, and anti-virals have been established, they do not specifically target the resulting inflammatory response and complications the virus causes.
This study aims to evaluate how safe and effective a particular oral medication, Belnacasan, is in diminishing your body's inflammatory response, which may go into overdrive when infected with the virus. This overly activated immune response can become uncontrolled resulting in cell death and the release of damaging proteins which can cause major harm to all organs throughout the body.
Belnacasan prevents the activation of a particular enzyme, Caspase-1, which plays a major role in activating this damaging immune response brought on by COVID-19. The goal of this medication being a more targeted treatment that aims to prevent the devastating immune response.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
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Subject (or legally authorized representative) provides written informed consent prior to the initiation of any study procedures
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Subject understands and agrees to comply with planned study procedures, including using the diary
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Subject agrees to the collection of nasopharyngeal swabs and venous blood per protocol
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Subject is male or non-pregnant female adult ≥18 years of age at time of consent
a. Women with a history of menstruation must agree to use two methods of contraception, at least one of which is highly effective, for the duration of the study as well as to undergo additional pregnancy testing during the study
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Subject has a laboratory confirmed SARS-CoV-2 infection as determined by RT-PCR assay prior to enrollment
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Subject has evidence of either mild or moderate COVID-19 illness of less than 7 days from first onset, with minimal baseline symptom severity based on patient-reported FDA scoring system defined as follows:
- Subject presents with at least two common symptoms of COVID-19 from the following list: 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 with exertion (without supplemental oxygen requirement) with a score of 2 or higher, impairment in sense of smell or taste with a score of 1 or higher OR
- Subject presents with any (i.e., at least one) symptom of COVID-19 as defined above AND clinical evidence of moderate COVID-19 as defined by FDA guidance for industry (such as respiratory rate >20 breaths per minute, heart rate >90 beats per minute, with oxygen saturation >93% on room air at sea level)
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Subject presents with high-risk for COVID-19-related inflammation determined by at least one comorbidity, including obesity, diabetes, hypertension, stable heart disease, respiratory disease, and/or non-severe fatty liver disease
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Subject's overall health condition is deemed as suitable to fully and safely participate in this trial as determined by the investigator
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Any clinical signs indicative of severe or critical COVID-19 as defined by FDA guidance for Industry at the time, including SpO2 <93% and/or oxygen requirement
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Hospitalization for COVID-19, or consideration thereof
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ICU level of care and/or non-mechanical/mechanical ventilation and/or oxygen supplementation at time of enrollment
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Pregnant or breast-feeding subjects
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Subjects who cannot swallow tablets
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History of any pre-existing organ impairment, such as:
- Severe kidney disease (known or estimated GFR <30 mL/minute) or on dialysis
- Uncontrolled, clinically significant heart diseases such as arrhythmias, angina or heart failure as defined by AHA/ACC Grade C and D
- Chronic respiratory disease requiring supplemental oxygen
- Moderate and severe hepatic impairment as defined by Child-Pugh scoring Class B and Class C
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Elevated liver function test (determined by ALT, AST, GGT, or ALP >2x upper limit of normal, and/or total Bilirubin > upper limit of normal)
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History of malignancy or immunodeficiency within the prior 5 years
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Acute respiratory illness other than COVID-19
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Acute bacterial, viral or fungal infection (including HIV, hepatitis B, hepatitis C)
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While dosed with IP, the taking of prohibited concomitant medication or the ingestion of food that interferes with the IP, including:
- Non-COVID19-related anti-viral medication such as lopinavir, ritonavir, ribavirin, or interferon-1β
- Systemically administered immunosuppressive and anti-inflammatory agents, other than background standard of care for COVID-19 at the time
- Drugs and foods that are potent inhibitors or inducers of CYP3A4 and/or P-gp, as listed in FDA "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers", including herbal medications such as St. John's Wort within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
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Any other diseases or medical conditions or concomitant medications that are deemed as not compatible or appropriate for the subject's ability to fully and safely participate in this trial as determined by the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Interventional Belnacasan 900mg dose TID Administration Total: 2700mg Placebo Placebo 0 mg dose TID Administration Total: 0 mg
- Primary Outcome Measures
Name Time Method Safety and Tolerability of Belnacasan Through 60 days post enrollment Number of adverse events and serious adverse events
- Secondary Outcome Measures
Name Time Method Sustained Recovery and Resolution Rates of Common COVID-19 Symptoms 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.
Sustained Improvement of Global Impression Rates 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)?"
Time to Sustained Recovery or Resolution of Common COVID-19 Symptoms 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.
Time to Sustained Improvement of Global Impression 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.
Rates of Fever 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.
Oxygenation Levels Over 60 days post randomization Average change from baseline over 60 days in percentage of blood saturation
Time in Days to Normalization of Fever and Oxygenation Levels. 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 enrollment; with oxygenation of SpO2\>= 96% or SpO2\>93% in room air, when resting, in total during the first 28 days post randomization.
Experiences of COVID-19 Related Deterioration and Mortality 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.
The Number of Subjects With COVID-19 Related Deterioration and Mortality Experiences 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.
Changes on the WHO 9-Point Ordinal Scale 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 \[0: Uninfected or "no clinical or virological evidence of infection"; 1: Not hospitalized, no limitations on activities; 2: Not hospitalized, limitation on activities; 3: Hospitalized, not requiring supplemental oxygen; 4: Hospitalized, requiring supplemental oxygen; 5: Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6: Hospitalized, intubated; 7: Hospitalized, advanced life support including invasive mechanical ventilation or ECMO; 8: Death\] had experienced an improvement from scale 2 to scale 1 or 0; an improvement from scale 1 to scale 0 ; a sustainment from scale 1 to scale 1; any improvement of the scale; any worsening of the scale; scale 4 or higher; scale 6 or higher.
Values on the WHO 9-Point Ordinal Scale 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 COVID-19 illness)?"
1. Not hospitalized, no limitations on activities
* defined as subject answering "Yes" to "In the past 24 hours, have you returned to your usual activities (before your COVID-19 illness)?" 2. Not hospitalized, limitation on activities
* defined as subject answering "No" to "In the past 24 hours, have you returned to your usual actTime to Improvement on the WHO 9-Point Ordinal Scale Post treatment to Day 60 Comparison of treatment group versus placebo group, respectively, in the mean number of days from enrollment to reporting "no limitations" or "uninfected". The discrepancy in patient numbers (enrolled versus analyzed) is due to patients who either dropped out or have missing data.
Mean Number of Days of Experiencing WHO 9-Point Ordinal Scale Values Post treatment through Day 60 Comparison of treatment group versus placebo group, respectively, in the mean number of days on which subjects experienced "limitations", "no limitations", and "uninfected" post treatment (60 Days).
IL-6 Baseline and Days 7, 14, 21, 28 Plasma levels of IL-6
IL-1ra Baseline and Days 7, 14, 21, 28 Measurement of plasma IL-1ra levels
IL-18 Baseline and Days 7, 14, 21, and 28 Measurement of plasma levels of IL-18
TNF-alpha Baseline and Days 7, 14, 21, and 28 Plasma levels of TNF-alpha
Caspase-1 Baseline and Days 7, 14, 21, and 28 Plasma levels of caspase-1
Gasdermin D Baseline and Days 7, 14, 21, and 28 Plasma levels of gasdermin D
G-CSF Baseline and Days 7, 14, 21, and 28 Plasma levels of G-CSF
Trial Locations
- Locations (2)
MedStar Franklin Square
🇺🇸Baltimore, Maryland, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States