A Proof of Concept, Randomized, Double-blind, Placebo-controlled Trial of Orally Administered Belnacasan Tablets for the Treatment of Mild to Moderate COVID-19
Overview
- Phase
- Phase 2
- Intervention
- Belnacasan
- Conditions
- COVID-19
- Sponsor
- MedStar Health
- Enrollment
- 43
- Locations
- 2
- Primary Endpoint
- Safety and Tolerability of Belnacasan
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject (or legally authorized representative) provides written informed consent prior to the initiation of any study procedures
- •Subject understands and agrees to comply with planned study procedures, including using the diary
- •Subject agrees to the collection of nasopharyngeal swabs and venous blood per protocol
- •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
- •Subject has a laboratory confirmed SARS-CoV-2 infection as determined by RT-PCR assay prior to enrollment
- •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)
- •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
Exclusion Criteria
- •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
- •Hospitalization for COVID-19, or consideration thereof
- •ICU level of care and/or non-mechanical/mechanical ventilation and/or oxygen supplementation at time of enrollment
- •Pregnant or breast-feeding subjects
- •Subjects who cannot swallow tablets
- •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
Arms & Interventions
Interventional
900mg dose TID Administration Total: 2700mg
Intervention: Belnacasan
Placebo
0 mg dose TID Administration Total: 0 mg
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and Tolerability of Belnacasan
Time Frame: Through 60 days post enrollment
Number of adverse events and serious adverse events
Secondary Outcomes
- Sustained Recovery and Resolution Rates of Common COVID-19 Symptoms(Baseline and Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization)
- Sustained Improvement of Global Impression Rates(Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization)
- Time to Sustained Recovery or Resolution of Common COVID-19 Symptoms(Over 60 days post randomization)
- Time to Sustained Improvement of Global Impression(Over 60 days post randomization)
- Rates of Fever(Days between enrollment and day 2 post randomization)
- Oxygenation Levels(Over 60 days post randomization)
- Time in Days to Normalization of Fever and Oxygenation Levels.(28 Days)
- Experiences of COVID-19 Related Deterioration and Mortality(Days 14, 28 and 60 post randomization)
- The Number of Subjects With COVID-19 Related Deterioration and Mortality Experiences(Over 28 days)
- Changes on the WHO 9-Point Ordinal Scale(Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization)
- Values on the WHO 9-Point Ordinal Scale(Days 14, 28, and 60 post randomization)
- Time to Improvement on the WHO 9-Point Ordinal Scale(Post treatment to Day 60)
- Mean Number of Days of Experiencing WHO 9-Point Ordinal Scale Values(Post treatment through Day 60)
- IL-6(Baseline and Days 7, 14, 21, 28)
- IL-1ra(Baseline and Days 7, 14, 21, 28)
- Gasdermin D(Baseline and Days 7, 14, 21, and 28)
- IL-18(Baseline and Days 7, 14, 21, and 28)
- TNF-alpha(Baseline and Days 7, 14, 21, and 28)
- Caspase-1(Baseline and Days 7, 14, 21, and 28)
- G-CSF(Baseline and Days 7, 14, 21, and 28)