Covid19Phase 2NCT04540120
Safety and Efficacy of Dapansutrile for Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome
A Phase 2 study testing dapansutrile capsules in people with Covid19 and Cytokine Release Syndrome, run by Olatec Therapeutics, Inc. at 10 sites in 2 countries.
Trial summary
The purpose of this study is to assess the safety and efficacy of orally administered NLRP3 inhibitor, dapansutrile, for the treatment of moderate COVID-19 symptoms and early cytokine release syndrome (CRS) in patients with confirmed SARS-CoV-2 infection and moderate symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Cytokine Release Syndrome
- What is being tested?
- dapansutrile capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 24 Sep 2020to 28 Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Male and female subjects ≥ 18 years of age;
- SARS-CoV-2-positive, confirmed by Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-authorized COVID-19 test ≤ 7 days prior to randomization;
- Less than or equal to 7 days from first symptom onset to randomization;
- Subjects with moderate COVID-19 consistent with the definition of "moderate" as set forth by the February 2021 FDA Guidance for Industry: COVID-19: Developing Drugs and Biological Products for Treatment or
- Prevention (FDA, 2021) who at the Screening/Baseline/Day 1 Visit:
- have felt feverish within the past 24 hours,
Show all 20Show fewer
- have an SpO2 > 93% on room air at sea level when sitting, and
- meet at least one of the following criteria: i). Respiratory rate: ≥ 20 breaths/minute, when the subject is sitting, ii). SpO2: ≤ 96% on room air at sea level, when the subject is sitting, iii). Shortness of breath: with exertion, not requiring oxygen, or vi). Heart rate: ≥ 90 beats/minute, when the subject is sitting;
- If all the criteria in Inclusion 4c are met, subject must possess at least one of the following high-risk conditions known to have an underlying increased level of cytokine production; otherwise, at least two of these high-risk conditions must be met:
- 70 years or more of age,
- Obesity (BMI ≥ 30 kg/m2),
- Diabetes (type 1 or 2),
- Uncontrolled hypertension, defined as diastolic > 100 mm Hg and/or systolic > 150 mm Hg without any current anti-hypertensive medications. At the time of screening if the subject is on anti- hypertensive medication(s) and diastolic or systolic rates are elevated, subject may be enrolled after consultation with the Medical Monitor,
- Known respiratory disease (including asthma or chronic obstructive pulmonary disease [COPD]),
- Known heart failure (note: subjects with New York Heart Association Class IV congestive heart failure cannot be enrolled per Exclusion Criterion 4), or
- Known coronary disease;
- Plasma CRP level must be collected at Screening/Baseline/Day 1 Visit;
- Acceptable overall medical condition to be safely enrolled in and complete the study (with specific regard to cardiovascular, renal, and hepatic conditions) in the opinion of the Investigator;
- Ability to provide written, informed consent prior to initiation of any study- related procedures, and ability in the opinion of the Investigator to understand and comply with all the requirements of the study, which includes abstaining from the use of prohibited medications.
- Subject must present with at least moderate symptomatology, based on having symptoms in the prior 24 hours that were uncomfortable and interfered with daily activities or required treatment other than study drug and having at least one of the following symptoms: cough; fatigue; myalgia; diarrhea; vomiting; nausea; headache; sore throat; nasal congestion; rhinorrhea; loss of taste; loss of smell; fainting; or chills, shivering, and/or sweating.
Who cannot join
- Women of childbearing potential, or men whose sexual partner(s) is a woman of childbearing potential, who:
- Are or intend to become pregnant (including use of fertility drugs) during the study;
- Are nursing (female subjects only);
- Are not using an acceptable, highly effective method of contraception until all follow-up procedures are complete.
- Evidence of pre-existing or new-onset organ failure;
- Evidence of moderate concurrent nervous system, renal, endocrine, or gastrointestinal disease, unrelated to COVID-19 as determined by the Investigator;
Show all 30Show fewer
- Evidence of cardiovascular disease with significant arrhythmia, congestive heart failure (New York Heart Association Class IV), unstable angina, cor pulmonale, or symptomatic pericardial effusion, not related to COVID-19 as determined by the Investigator;
- Required use of vasoactive drug support;
- History of myocardial infarction in the 6 months prior to the Screening/Baseline/Day 1 Visit;
- Evidence of current liver disease, not related to COVID-19 as determined by the investigator;
- History or evidence of active tuberculosis (TB) infection at Screening/Baseline/Day 1 Visit or one of the risk factors for tuberculosis such as but not limited or exclusive to:
- History of any of the following: residence in a congregate setting (e.g., jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g., injection or non-injection), health-care workers with unprotected exposure to subjects who are at high risk of TB or subjects with TB disease before the identification and correct airborne precautions of the subject or
- Close contact (i.e., share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease within the last 12 months.
- History of or currently active primary or secondary immunodeficiency;
- Past or present requirement for oxygen (e.g., nasal cannula, proning, mechanical ventilation and/or supplemental oxygen).
- Use of any prohibited concomitant medications/therapies over the defined or planned use of any concomitant medications/therapies during the
- Treatment Period, including specifically:
- use of ibuprofen or diclofenac
- use of colchicine
- use of systemic steroids within 30 days of randomization
- use of janus kinase (JAK) inhibitors
- use of off-label agents (e.g., hydroxychloroquine, remdesivir, dexamethasone) and biologic and oral anti-cytokine agents (e.g., current treatment with adalimumab, infliximab, etanercept, golimumab, certolizumab pegol, tocilizumab, sarilumab, anakinra, canakinumab, rilonacept, baricitinib, tofacitinib, or upadacitinib);
- Note: During the treatment period a patient may meet the criteria for a treatment approved by the FDA specifically for COVID-19 (e.g. remdesivir). In this situation the investigator and medical monitor should confer and take the most appropriate decision for the patient. If possible, the preference would be for the patient to complete the 14 days of dosing before adding on the 2nd treatment. If that is not possible the preference would be for the patient to continue their 14 days on dapansutrile and complete all study related visits.
- Known history of renal impairment (e.g., calculated glomerular filtration rate [GFR] < 45 mL/min);
- Evidence of malignant disease, or malignancies diagnosed within the previous 5 years (except for local basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured);
- History of infection or known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV);
- Any other concomitant medical or psychiatric conditions, diseases, or prior surgeries that, in the opinion of the Investigator, would impair the subject from safely participating in the trial and/or completing protocol requirements;
- Individuals who have been in a chronic care facility in the past 30 days;
- Individuals who are incarcerated;
- Participation in any clinical trial and/or use of any investigational product within the immediate 30-day period prior to the Screening/Baseline//Day 1 Visit; or receipt prior to Screening/Baseline/Day 1 Visit or intending to receive during the trial a COVID-19 vaccination.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
PanAmerican Clinical Research LLC
Brownsville, Texas, 78520
J & S Studies, Inc.
College Station, Texas, 77645
C&R Research Services USA
Coral Gables, Florida, 33134
Invesclinic U.S. LLC
Fort Lauderdale, Florida, 33308
Inpatient Research Clinic, LLC
Hialeah, Florida, 33013
C&R Research Services USA
Houston, Texas, 77023
Las Vegas Medical Research, LLC
Las Vegas, Nevada, 89113
Texas Research Alliance LLC
McAllen, Texas, 78503
Sunrise Research Institute
Sunrise, Florida, 33325
About this study
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Orally Administered Dapansutrile Capsules for the Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome
The purpose of this study is to assess the safety and efficacy of orally administered NLRP3 inhibitor, dapansutrile, for the treatment of moderate COVID-19 symptoms and early cytokine release syndrome (CRS) in patients with confirmed SARS-CoV-2 infection and moderate symptoms.
Coronavirus disease 2019 (COVID-19) is caused by infection from a new strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by fever, cough and shortness of breath, which in certain patients can lead to systemic organ failure and mortality.
Read more
The data show that SARS-CoV-2 activates the innate immune signaling sensor NLRP3. Activation of NLRP3 initiates the cytokine release syndrome (CRS), which includes the production of primary cytokine, IL-1, triggering an intense inflammatory response that is prevalent in symptomatic COVID-19 patients. When CRS advances further to a fulminant 'cytokine storm', the data show that respiratory distress syndrome and multiple-organ failure take place.
A specific inhibitor of NLRP3, dapansutrile may reduce or prevent the hyperinflammation associated with CRS by inhibiting the production of IL-1β early to arrest the progression to a severe 'cytokine storm.' The end result would be a reduction in the need for COVID-19 patients to receive intensive medical treatment, allowing for fewer hospitalizations, administration of mechanical ventilation and deaths.
Read the detailed description
This is a Phase 2, randomized, double-blind, placebo-controlled study evaluating dapansutrile versus placebo. Approximately 80 subjects randomized 1:1 (40 dapansutrile, 40 placebo) are planned to be enrolled.
At the Screening/Baseline/Day 1 Visit, subjects will provide informed consent, be screened for eligibility, and be randomized/enrolled into the study. Subjects will also receive the first dose of study drug at this visit once study eligibility has been confirmed, and the second dose of study drug will be taken approximately 12 hours after the first dose. Study drug will be continued twice daily (morning and evening doses) through Day 14.
The trial duration will be approximately 45 days for all subjects enrolled, with assessments as follows: Screening/Baseline/Day 1, Day 4 (±1 day), Day 8 (±1 day), Day 15 (±1 day), Day 29 (±3 days), and Day 45 (± 3 days). The Day 29 and Day 45 follow-up visits will be conducted virtually via the institution's telehealth process.
Each subject will be asked to maintain two paper diaries at home daily for the first 14 days: a dosing diary and a subject diary. The dosing diary will be used to record the number of capsules taken each morning and evening. The subject diary will be used to record temperature, oxygen levels, COVID-19 symptoms, and overall health (using the prior 24-hour period for parameters requiring subject recall). The set of questions used in the subject diary will also be administered to the subjects at the Screening/Baseline/Day 1 Visit (pre-dose), Day 15, Day 29, and Day 45 visits. Each subject will be provided a no-contact thermometer and a hand-held pulse oximeter at the Screening/Baseline/Day 1 Visit for home use.
At Day 29 and Day 45, additional assessments of safety and clinical activity will occur. The Day 29 and Day 45 follow-up visits will be conducted virtually via the sites' telehealth process.
- Conditions
- Covid19, Cytokine Release Syndrome
- Being tested
- dapansutrile capsules, placebo capsules
- Keywords
- NLRP3, Covid19, Cytokine Release Syndrome, Dapansutrile
- Medical subject headings
- COVID-19, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dapansutrile capsulesDrug
Also called OLT1177 capsules
Hard opaque capsules containing 250 mg of API.
placebo capsulesDrug
Hard opaque capsules containing 0 mg of API.
| Study group | Role | What they receive |
|---|---|---|
| dapansutrile capsules | Experimental | Subjects will receive 4 x 250mg dapansutrile capsules BID for 14 days with an initial (first) dose of 8 x 250mg (2000 mg) administered at the study site on Day 1 (Day 1 dose may be 3000 mg). Receives: Drug: dapansutrile capsules |
| placebo capsules | Placebo comparator | Subjects will receive 4 placebo capsules BID for 14 days with an initial (first) dose of 8 capsules administered at the study site on Day 1. Receives: Drug: placebo capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with clinical deterioration
Clinical deterioration is defined as having any COVID-19-related hospitalization after enrollment or both (1) worsening or persistence of shortness of breath and (2) oxygen saturation less than 92% on room air at sea level or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.
Measured: Day 15
Secondary outcomes (42)
Proportion of subjects with complete resolution of fever symptoms and shortness of breath
Complete resolution is defined as having a symptom described as "absent" on the subject diary with no return of the symptom before Day 45.
Measured: Day 8, Day 15, Day 29, Day 45
Cumulative incidence of SAEs
Evaluate the cumulative incidence of SAEs of dapansutrile relative to placebo
Measured: Day 45
Cumulative incidence of Grade 3 and Grade 4 Adverse Events
Evaluate the cumulative incidence of Grade 3 and Grade 4 Adverse Events of dapansutrile relative to placebo
Measured: Day 45
Discontinuation or temporary suspension of participation
Evaluate the cumulative incidence of discontinuation or temporary suspension (for any reason) of dapansutrile relative to placebo
Measured: Day 45
Changes in white cell count
Evaluate changes in white cell count of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in hemoglobin
Evaluate changes in hemoglobin of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in platelets
Evaluate changes in platelets of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in creatinine
Evaluate changes in creatinine of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in glucose
Evaluate changes in glucose of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in total bilirubin
Evaluate changes in total bilirubin of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in ALT
Evaluate changes in ALT of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Changes in AST
Evaluate changes in AST of dapansutrile relative to placebo over time
Measured: Day 8, Day 15
Incidence of new infection that occurs during the study
Evaluate changes in incidence of new infection that occurs during the study of dapansutrile relative to placebo
Measured: Day 8, Day 15
Incidence of opportunistic infections
Evaluate changes in incidence of opportunistic infections of dapansutrile relative to placebo
Measured: Day 8, Day 15
Time to clinical improvement
Time to clinical improvement in fever symptoms and shortness of breath
Measured: Baseline/Day 1 to Day 15
Time to sustained absence of fever
Time to sustained absence of fever, defined as at least 2 days since last temperature measurement of ≥ 38˚C (100.4°F)
Measured: Baseline/Day 1 to Day 15
Clinical improvement in symptoms relevant to COVID 19
Proportion of subjects who experience clinical improvement in symptoms relevant to COVID 19 (e.g., cough, diarrhea, vomiting)
Measured: Day 15
Incidence of hospitalization, supplemental oxygen, mechanical ventilation, or death before Day 15
Incidence of subjects meeting the composite endpoint of subjects requiring hospitalization (hospitalization is defined as ≥ 24 hours of acute care), supplemental oxygen, mechanical ventilation, or who die
Measured: Day 15
Duration of hospitalization, supplemental oxygen or mechanical ventilation before Day 15
Duration of incidences of subjects meeting the composite endpoint of subjects requiring hospitalization (hospitalization is defined as ≥ 24 hours of acute care), supplemental oxygen or mechanical ventilation
Measured: Day 15
Clinical improvement in symptoms
Proportion of subjects who experience clinical improvement in symptoms by Day 15, defined as a reduction of two or more points on the WHO Ordinal Scale for Clinical Improvement (lowest score between Baseline Visit/Day 1 and Day 15)
Measured: Baseline/Day 1 to Day 15
Improvement in oxygenation
Improvement in oxygenation over the course of the study and maintenance of this effect
Measured: Baseline/Day 1 to Day 15
Change in ALT
Assess and compare change from Baseline in AST
Measured: Baseline/Day 1 to Day 15
Change in AST
Assess and compare change from Baseline in AST
Measured: Baseline/Day 1 to Day 15
Change in blood glucose
Assess and compare change from Baseline in blood glucose
Measured: Baseline/Day 1 to Day 15
Change in Erythrocyte Sedimentation Rate (ESR)
Assess and compare change from Baseline in Erythrocyte Sedimentation Rate (ESR)
Measured: Baseline/Day 1 to Day 15
Change in Hemoglobin A1c (HbA1C)
Assess and compare change from Baseline in Hemoglobin A1c (HbA1C)
Measured: Baseline/Day 1 to Day 15
Change in Lactate dehydrogenase (LDH)
Assess and compare change from Baseline in Lactate dehydrogenase (LDH)
Measured: Baseline/Day 1 to Day 15
Change in Lymphocyte, Absolute count
Assess and compare change from Baseline in Lymphocyte, Absolute count
Measured: Baseline/Day 1 to Day 15
Change in Monocyte, Absolute count
Assess and compare change from Baseline in Monocyte, Absolute count
Measured: Baseline/Day 1 to Day 15
Change in Neutrophils, Absolute count
Assess and compare change from Baseline in Neutrophils, Absolute count
Measured: Baseline/Day 1 to Day 15
Change in Eosinophil, Absolute count
Assess and compare change from Baseline in Eosinophil, Absolute count
Measured: Baseline/Day 1 to Day 15
Change in CRP
Assess and compare change from Baseline in CRP
Measured: Baseline/Day 1 to Day 15
Change in D-Dimer
Assess and compare change from Baseline in D-Dimer
Measured: Baseline/Day 1 to Day 15
Change in Ferritin
Assess and compare change from Baseline in Ferritin
Measured: Baseline/Day 1 to Day 15
Change in Fibrinogen
Assess and compare change from Baseline in Fibrinogen
Measured: Baseline/Day 1 to Day 15
Change in Partial Thromboplastin Time (PTT) and International Normalized Ratio (INR)
Assess and compare change from Baseline in Partial Thromboplastin Time (PTT) and International Normalized Ratio (INR)
Measured: Baseline/Day 1 to Day 15
Change in IL-1β
Assess and compare change from Baseline in IL-1β
Measured: Baseline/Day 1 to Day 15
Change in IL-6
Assess and compare change from Baseline in IL-6
Measured: Baseline/Day 1 to Day 15
Change in IL-18
Assess and compare change from Baseline in IL-18
Measured: Baseline/Day 1 to Day 15
Change in granulocyte colony-stimulating factor (G-CSF)
Assess and compare change from Baseline in granulocyte colony-stimulating factor (G-CSF)
Measured: Baseline/Day 1 to Day 15
Change in interferon-γ-induced protein 10 (IP-10)
Assess and compare change from Baseline in interferon-γ-induced protein 10 (IP-10)
Measured: Baseline/Day 1 to Day 15
Change in C3a
Assess and compare change from Baseline in C3a
Measured: Baseline/Day 1 to Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2020
- Study start24 Sep 2020
- Primary completion28 Jul 2022
- Study completion28 Jul 2022
Why it stopped: Terminated due to the treatment environment for COVID-19 evolving with the pervasiveness of vaccinations and other therapeutic modalities in mitigating against severe infection that has eliminated a viable patient population for study enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies 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
- Model description
- Subjects will be assigned to receive either dapansutrile capsules or placebo capsules in a 1:1 ratio.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Olatec Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CTI Clinical Trial and Consulting Services
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04540120
- Sponsor's protocol ID
- OLT1177-10
- Status last verified
- Apr 2023
- First submitted
- 13 Aug 2020
- Last updated
- 13 Apr 2023
- Results posted
- No
- 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 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Orally Administered Dapansutrile Capsules for the Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome
- ClinicalTrials.gov ID
- NCT04540120
- Acronym / sponsor ID
- OLT1177-10
- Conditions
- Covid19, Cytokine Release Syndrome
- Keywords
- NLRP3, Covid19, Cytokine Release Syndrome, Dapansutrile
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to the treatment environment for COVID-19 evolving with the pervasiveness of vaccinations and other therapeutic modalities in mitigating against severe infection that has eliminated a viable patient population for study enrollment.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Olatec Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- CTI Clinical Trial and Consulting Services
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 28 Jul 2022 (actual)
- Study completion
- 28 Jul 2022 (actual)
- First posted
- 7 Sep 2020 (actual)
- Results
- Not posted in the source record
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 study is to assess the safety and efficacy of orally administered NLRP3 inhibitor, dapansutrile, for the treatment of moderate COVID-19 symptoms and early cytokine release syndrome (CRS) in patients with confirmed SARS-CoV-2 infection and moderate symptoms.
Coronavirus disease 2019 (COVID-19) is caused by infection from a new strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by fever, cough and shortness of breath, which in certain patients can lead to systemic organ failure and mortality.
The data show that SARS-CoV-2 activates the innate immune signaling sensor NLRP3. Activation of NLRP3 initiates the cytokine release syndrome (CRS), which includes the production of primary cytokine, IL-1, triggering an intense inflammatory response that is prevalent in symptomatic COVID-19 patients. When CRS advances further to a fulminant 'cytokine storm', the data show that respiratory distress syndrome and multiple-organ failure take place.
A specific inhibitor of NLRP3, dapansutrile may reduce or prevent the hyperinflammation associated with CRS by inhibiting the production of IL-1β early to arrest the progression to a severe 'cytokine storm.' The end result would be a reduction in the need for COVID-19 patients to receive intensive medical treatment, allowing for fewer hospitalizations, administration of mechanical ventilation and deaths.
Detailed description
This is a Phase 2, randomized, double-blind, placebo-controlled study evaluating dapansutrile versus placebo. Approximately 80 subjects randomized 1:1 (40 dapansutrile, 40 placebo) are planned to be enrolled.
At the Screening/Baseline/Day 1 Visit, subjects will provide informed consent, be screened for eligibility, and be randomized/enrolled into the study. Subjects will also receive the first dose of study drug at this visit once study eligibility has been confirmed, and the second dose of study drug will be taken approximately 12 hours after the first dose. Study drug will be continued twice daily (morning and evening doses) through Day 14.
The trial duration will be approximately 45 days for all subjects enrolled, with assessments as follows: Screening/Baseline/Day 1, Day 4 (±1 day), Day 8 (±1 day), Day 15 (±1 day), Day 29 (±3 days), and Day 45 (± 3 days). The Day 29 and Day 45 follow-up visits will be conducted virtually via the institution's telehealth process.
Each subject will be asked to maintain two paper diaries at home daily for the first 14 days: a dosing diary and a subject diary. The dosing diary will be used to record the number of capsules taken each morning and evening. The subject diary will be used to record temperature, oxygen levels, COVID-19 symptoms, and overall health (using the prior 24-hour period for parameters requiring subject recall). The set of questions used in the subject diary will also be administered to the subjects at the Screening/Baseline/Day 1 Visit (pre-dose), Day 15, Day 29, and Day 45 visits. Each subject will be provided a no-contact thermometer and a hand-held pulse oximeter at the Screening/Baseline/Day 1 Visit for home use.
At Day 29 and Day 45, additional assessments of safety and clinical activity will occur. The Day 29 and Day 45 follow-up visits will be conducted virtually via the sites' telehealth process.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Subjects will be assigned to receive either dapansutrile capsules or placebo capsules in a 1:1 ratio.
| Arm | Type | Receives |
|---|---|---|
| dapansutrile capsules | Experimental | Drug: dapansutrile capsulesSubjects will receive 4 x 250mg dapansutrile capsules BID for 14 days with an initial (first) dose of 8 x 250mg (2000 mg) administered at the study site on Day 1 (Day 1 dose may be 3000 mg). |
| placebo capsules | Placebo comparator | Drug: placebo capsulesSubjects will receive 4 placebo capsules BID for 14 days with an initial (first) dose of 8 capsules administered at the study site on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Male and female subjects ≥ 18 years of age;
- SARS-CoV-2-positive, confirmed by Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-authorized COVID-19 test ≤ 7 days prior to randomization;
- Less than or equal to 7 days from first symptom onset to randomization;
- Subjects with moderate COVID-19 consistent with the definition of "moderate" as set forth by the February 2021 FDA Guidance for Industry: COVID-19: Developing Drugs and Biological Products for Treatment or
- If all the criteria in Inclusion 4c are met, subject must possess at least one of the following high-risk conditions known to have an underlying increased level of cytokine production; otherwise, at least two of these high-risk conditions must be met:
Key exclusion criteria (30 listed)
- Women of childbearing potential, or men whose sexual partner(s) is a woman of childbearing potential, who:
- Evidence of pre-existing or new-onset organ failure;
- Evidence of moderate concurrent nervous system, renal, endocrine, or gastrointestinal disease, unrelated to COVID-19 as determined by the Investigator;
- Evidence of cardiovascular disease with significant arrhythmia, congestive heart failure (New York Heart Association Class IV), unstable angina, cor pulmonale, or symptomatic pericardial effusion, not related to COVID-19 as determined by the Investigator;
- Required use of vasoactive drug support;
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 |
|---|---|---|
| dapansutrile capsulesAlso: OLT1177 capsulesHard opaque capsules containing 250 mg of API. | Drug | dapansutrile capsules |
| placebo capsulesHard opaque capsules containing 0 mg of API. | Drug | placebo capsules |
Primary outcome
Proportion of subjects with clinical deterioration
Time frame: Day 15
Clinical deterioration is defined as having any COVID-19-related hospitalization after enrollment or both (1) worsening or persistence of shortness of breath and (2) oxygen saturation less than 92% on room air at sea level or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.
42 secondary outcomes
Proportion of subjects with complete resolution of fever symptoms and shortness of breath
Time frame: Day 8, Day 15, Day 29, Day 45
Cumulative incidence of SAEs
Time frame: Day 45
Cumulative incidence of Grade 3 and Grade 4 Adverse Events
Time frame: Day 45
Discontinuation or temporary suspension of participation
Time frame: Day 45
Changes in white cell count
Time frame: Day 8, Day 15
Changes in hemoglobin
Time frame: Day 8, Day 15
Changes in platelets
Time frame: Day 8, Day 15
Changes in creatinine
Time frame: Day 8, Day 15
Changes in glucose
Time frame: Day 8, Day 15
Changes in total bilirubin
Time frame: Day 8, Day 15
Changes in ALT
Time frame: Day 8, Day 15
Changes in AST
Time frame: Day 8, Day 15
Incidence of new infection that occurs during the study
Time frame: Day 8, Day 15
Incidence of opportunistic infections
Time frame: Day 8, Day 15
Time to clinical improvement
Time frame: Baseline/Day 1 to Day 15
Time to sustained absence of fever
Time frame: Baseline/Day 1 to Day 15
Clinical improvement in symptoms relevant to COVID 19
Time frame: Day 15
Incidence of hospitalization, supplemental oxygen, mechanical ventilation, or death before Day 15
Time frame: Day 15
Duration of hospitalization, supplemental oxygen or mechanical ventilation before Day 15
Time frame: Day 15
Clinical improvement in symptoms
Time frame: Baseline/Day 1 to Day 15
Improvement in oxygenation
Time frame: Baseline/Day 1 to Day 15
Change in ALT
Time frame: Baseline/Day 1 to Day 15
Change in AST
Time frame: Baseline/Day 1 to Day 15
Change in blood glucose
Time frame: Baseline/Day 1 to Day 15
Change in Erythrocyte Sedimentation Rate (ESR)
Time frame: Baseline/Day 1 to Day 15
Change in Hemoglobin A1c (HbA1C)
Time frame: Baseline/Day 1 to Day 15
Change in Lactate dehydrogenase (LDH)
Time frame: Baseline/Day 1 to Day 15
Change in Lymphocyte, Absolute count
Time frame: Baseline/Day 1 to Day 15
Change in Monocyte, Absolute count
Time frame: Baseline/Day 1 to Day 15
Change in Neutrophils, Absolute count
Time frame: Baseline/Day 1 to Day 15
Change in Eosinophil, Absolute count
Time frame: Baseline/Day 1 to Day 15
Change in CRP
Time frame: Baseline/Day 1 to Day 15
Change in D-Dimer
Time frame: Baseline/Day 1 to Day 15
Change in Ferritin
Time frame: Baseline/Day 1 to Day 15
Change in Fibrinogen
Time frame: Baseline/Day 1 to Day 15
Change in Partial Thromboplastin Time (PTT) and International Normalized Ratio (INR)
Time frame: Baseline/Day 1 to Day 15
Change in IL-1β
Time frame: Baseline/Day 1 to Day 15
Change in IL-6
Time frame: Baseline/Day 1 to Day 15
Change in IL-18
Time frame: Baseline/Day 1 to Day 15
Change in granulocyte colony-stimulating factor (G-CSF)
Time frame: Baseline/Day 1 to Day 15
Results and safety
The study was stopped early (reason given: Terminated due to the treatment environment for COVID-19 evolving with the pervasiveness of vaccinations and other therapeutic modalities in mitigating against severe infection that has eliminated a viable patient population for study enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2023.
Related trials for Covid19
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.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dapansutrile capsules in people with Covid19 and Cytokine Release Syndrome, run by Olatec Therapeutics, Inc. at 10 sites in 2 countries.
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 20 inclusion and 30 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: stopped early, as of the sponsor's last update on 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Switzerland. 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?
The study was stopped early (reason given: Terminated due to the treatment environment for COVID-19 evolving with the pervasiveness of vaccinations and other therapeutic modalities in mitigating against severe infection that has eliminated a viable patient population for study enrollment.). Results are not available in the source record.
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?
Proportion of subjects with clinical deterioration (time frame: Day 15). 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 13 Apr 2023.