COVID-19Phase 2NCT05164120
Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19
A Phase 2 study testing Belnacasan in people with COVID-19, run by MedStar Health at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Belnacasan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Dec 2021to 11 Oct 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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
Show all 11Show fewer
- 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
- Subject's overall health condition is deemed as suitable to fully and safely participate in this trial as determined by the investigator
Who cannot join
- 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:
Show all 19Show fewer
- 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
- Elevated liver function test (determined by ALT, AST, GGT, or ALP >2x upper limit of normal, and/or total Bilirubin > upper limit of normal)
- History of malignancy or immunodeficiency within the prior 5 years
- Acute respiratory illness other than COVID-19
- Acute bacterial, viral or fungal infection (including HIV, hepatitis B, hepatitis C)
- 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
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
MedStar Franklin Square
Baltimore, Maryland, 21237
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Proof of Concept, Randomized, Double-blind, Placebo-controlled Trial of Orally Administered Belnacasan Tablets for the Treatment of Mild to Moderate COVID-19
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Belnacasan, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelnacasanDrug
Oral administration
PlaceboDrug
Tablet containing 0mg of API
| Study group | Role | What they receive |
|---|---|---|
| Interventional | Experimental | 900mg dose TID Administration Total: 2700mg Receives: Drug: Belnacasan |
| Placebo | Placebo comparator | 0 mg dose TID Administration Total: 0 mg Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of Belnacasan
Number of adverse events and serious adverse events
Measured: Through 60 days post enrollment
Secondary outcomes (20)
Sustained Recovery and Resolution Rates of Common COVID-19 Symptoms
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.
Measured: Baseline and Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization
Sustained Improvement of Global Impression Rates
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)?"
Measured: Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization
Time to Sustained Recovery or Resolution of Common COVID-19 Symptoms
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.
Measured: Over 60 days post randomization
Time to Sustained Improvement of Global Impression
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.
Measured: Over 60 days post randomization
Rates of Fever
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.
Measured: Days between enrollment and day 2 post randomization
Oxygenation Levels
Average change from baseline over 60 days in percentage of blood saturation
Measured: Over 60 days post randomization
Time in Days to Normalization of Fever and Oxygenation Levels.
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.
Measured: 28 Days
Experiences of COVID-19 Related Deterioration and Mortality
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.
Measured: Days 14, 28 and 60 post randomization
The Number of Subjects With COVID-19 Related Deterioration and Mortality Experiences
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.
Measured: Over 28 days
Changes on the WHO 9-Point Ordinal Scale
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.
Measured: Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization
Values on the WHO 9-Point Ordinal Scale
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:
- 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)?"
- 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 act
Measured: Days 14, 28, and 60 post randomization
Time to Improvement on the WHO 9-Point Ordinal Scale
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.
Measured: Post treatment to Day 60
Mean Number of Days of Experiencing WHO 9-Point Ordinal Scale Values
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).
Measured: Post treatment through Day 60
IL-6
Plasma levels of IL-6
Measured: Baseline and Days 7, 14, 21, 28
IL-1ra
Measurement of plasma IL-1ra levels
Measured: Baseline and Days 7, 14, 21, 28
IL-18
Measurement of plasma levels of IL-18
Measured: Baseline and Days 7, 14, 21, and 28
TNF-alpha
Plasma levels of TNF-alpha
Measured: Baseline and Days 7, 14, 21, and 28
Caspase-1
Plasma levels of caspase-1
Measured: Baseline and Days 7, 14, 21, and 28
Gasdermin D
Plasma levels of gasdermin D
Measured: Baseline and Days 7, 14, 21, and 28
G-CSF
Plasma levels of G-CSF
Measured: Baseline and Days 7, 14, 21, and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2021
- Study start14 Dec 2021
- Primary completion18 Jul 2022
- Study completion11 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedStar Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Glenn Wortmann, MD, Principal investigator, MedStar Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05164120
- Sponsor's protocol ID
- MedStar-COVID-19-belnacasan
- Status last verified
- Sep 2024
- First submitted
- 15 Dec 2021
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept, Randomized, Double-blind, Placebo-controlled Trial of Orally Administered Belnacasan Tablets for the Treatment of Mild to Moderate COVID-19
- ClinicalTrials.gov ID
- NCT05164120
- Acronym / sponsor ID
- MedStar-COVID-19-belnacasan
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- MedStar HealthUniversity, hospital or other
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- 18 Jul 2022 (actual)
- Study completion
- 11 Oct 2022 (actual)
- First posted
- 20 Dec 2021 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interventional | Experimental | Drug: Belnacasan900mg dose TID Administration Total: 2700mg |
| Placebo | Placebo comparator | Drug: Placebo0 mg dose TID Administration Total: 0 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- Subject has a laboratory confirmed SARS-CoV-2 infection as determined by RT-PCR assay prior to enrollment
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelnacasanOral administration | Drug | Interventional |
| PlaceboTablet containing 0mg of API | Drug | Placebo |
Primary outcome
Safety and Tolerability of Belnacasan
Time frame: Through 60 days post enrollment
Number of adverse events and serious adverse events
20 secondary outcomes
Sustained Recovery and Resolution Rates of Common COVID-19 Symptoms
Time frame: Baseline and Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization
Sustained Improvement of Global Impression Rates
Time frame: Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization
Time to Sustained Recovery or Resolution of Common COVID-19 Symptoms
Time frame: Over 60 days post randomization
Time to Sustained Improvement of Global Impression
Time frame: Over 60 days post randomization
Rates of Fever
Time frame: Days between enrollment and day 2 post randomization
Oxygenation Levels
Time frame: Over 60 days post randomization
Time in Days to Normalization of Fever and Oxygenation Levels.
Time frame: 28 Days
Experiences of COVID-19 Related Deterioration and Mortality
Time frame: Days 14, 28 and 60 post randomization
The Number of Subjects With COVID-19 Related Deterioration and Mortality Experiences
Time frame: Over 28 days
Changes on the WHO 9-Point Ordinal Scale
Time frame: Days 4, 7, 10, 14, 21, 28, 42, and 60 post randomization
Values on the WHO 9-Point Ordinal Scale
Time frame: Days 14, 28, and 60 post randomization
Time to Improvement on the WHO 9-Point Ordinal Scale
Time frame: Post treatment to Day 60
Mean Number of Days of Experiencing WHO 9-Point Ordinal Scale Values
Time frame: Post treatment through Day 60
IL-6
Time frame: Baseline and Days 7, 14, 21, 28
IL-1ra
Time frame: Baseline and Days 7, 14, 21, 28
IL-18
Time frame: Baseline and Days 7, 14, 21, and 28
TNF-alpha
Time frame: Baseline and Days 7, 14, 21, and 28
Caspase-1
Time frame: Baseline and Days 7, 14, 21, and 28
Gasdermin D
Time frame: Baseline and Days 7, 14, 21, and 28
G-CSF
Time frame: Baseline and Days 7, 14, 21, and 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for COVID-19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Glenn Wortmann, MD principal investigator
MedStar Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belnacasan in people with COVID-19, run by MedStar Health at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Belnacasan (time frame: Through 60 days post enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.