Safety and Efficacy of Dapansutrile for Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome

NCT04540120 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: OLT1177-10
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 10

Brief 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. 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.

Conditions

Covid19; Cytokine Release Syndrome

Keywords

NLRP3; Covid19; Cytokine Release Syndrome; Dapansutrile

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 15

Secondary Outcomes (42)

• Proportion of subjects with complete resolution of fever symptoms and shortness of breath

  Day 8, Day 15, Day 29, Day 45

• Cumulative incidence of SAEs

  Day 45

• Cumulative incidence of Grade 3 and Grade 4 Adverse Events

  Day 45

• Discontinuation or temporary suspension of participation

  Day 45

• Changes in white cell count

  Day 8, Day 15

Study Arms (2)

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).

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.

Drug: placebo capsules

Interventions

dapansutrile capsules DRUG

Hard opaque capsules containing 250 mg of API.

Also known as: OLT1177 capsules

dapansutrile capsules

placebo capsules DRUG

Hard opaque capsules containing 0 mg of API.

placebo capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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;
• 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 coronary disease;
• Plasma CRP level must be collected at Screening/Baseline/Day 1 Visit;

You may not qualify if:

• 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;
• 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).

Sponsors & Collaborators

• Olatec Therapeutics LLC: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (10)

C&R Research Services USA

Coral Gables, Florida, 33134, United States

Location

Invesclinic U.S. LLC

Fort Lauderdale, Florida, 33308, United States

Location

Inpatient Research Clinic, LLC

Hialeah, Florida, 33013, United States

Location

Sunrise Research Institute

Sunrise, Florida, 33325, United States

Location

Las Vegas Medical Research, LLC

Las Vegas, Nevada, 89113, United States

Location

PanAmerican Clinical Research LLC

Brownsville, Texas, 78520, United States

Location

J & S Studies, Inc.

College Station, Texas, 77645, United States

Location

C&R Research Services USA

Houston, Texas, 77023, United States

Location

Texas Research Alliance LLC

McAllen, Texas, 78503, United States

Location

University Hospital Basel

Basel, Switzerland

Location

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome

Interventions

dapansutrile

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a randomized, blinded, placebo-controlled study. Treatment allocation (to active or placebo treatment groups) will be blinded to all study participants, personnel, and investigators. Only the drug labeling personnel, unblinded pharmacist and DMC members may be unblinded to the treatment assignment. Also, in the event of an emergency, an unblinding envelope can be opened unmasking the treatment assignment to the PI.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be assigned to receive either dapansutrile capsules or placebo capsules in a 1:1 ratio.

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: September 7, 2020
• Study Start: September 24, 2020
• Primary Completion: July 28, 2022
• Study Completion: July 28, 2022
• Last Updated: April 13, 2023

Record last verified: 2023-04

Locations

CH (1); US (9)