This is a randomized, double-blind, placebo-controlled, multi-arm, multicenter, phase II trial design to allow a rapid efficacy and toxicity assessment of potential therapies (camostat mesilate and artemisia annua) immediately after COVID-19 positive testing in mild to moderate disease and high-risk factors such as diabetes, hypertension, and obesity among others.
Coronavirus Disease 2019 (COVID-19) is a highly contagious disease, caused by a novel
enveloped RNA beta-coronavirus, also known as severe acute respiratory syndrome coronavirus-2
(SARS-CoV-2). This disease has caused a global health crisis.
While the majority of patients with COVID-19 develop a mild or uncomplicated illness,
approximately 20-30% of hospitalized patients have required intensive care support and 5% of
those have multi-organ failure or shock. The case fatality rate ranges from 1 to 4% and it is
higher among those with pre-existing comorbid conditions (high-risk) such as cardiovascular
disease, diabetes mellitus, obesity, chronic respiratory disease, hypertension, and cancer.
To date, treatments for COVID-19 in high-risk individuals remain experimental and therapeutic
strategies to deal with the infection are at best supportive, with prevention aimed at
reducing transmission in the community as the best weapon. No proven therapies have been
demonstrated to prevent progression of COVID-19 to severe illness in confirmed outpatients
with COVID-19 and this is a critical unmet need for high-risk individuals and warrants study.
Furthermore, there are no effective medications for the use in outpatients with confirmed
mild to moderate COVID-19 disease.
This is a randomized, double-blind, placebo-controlled, multi-arm, multicenter, phase II
trial design to allow a rapid efficacy and toxicity assessment of potential therapies,
camostat mesilate (serine protease inhibitor) and Artemisia annua (unknown mechanism)
immediately after COVID-19 positive testing in mild to moderate disease and high-risk factors
such as diabetes, hypertension, and obesity among others. The hypothesis of this study is
that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus, such
as Artemisia annua and camostat, will reduce the rate of a composite outcome of
hospitalization due to COVID-19 pneumonia or the use of oxygen therapy; will be devoid of
additional moderate to severe toxicities; and will improve viral clearance at Day 14 in
high-risk individuals. The main hypothesis is that the clinical outcomes in COVID-19 infected
patients at higher risk of poor outcomes following infection will be improved compared to the
standard of care when introduced as an early intervention after diagnosis.
Drug: Camostat Mesilate
Tablets
Other Name: Camostat
Drug: Artemisia Annua Leaf
Tea bags
Other Name: Array
Inclusion Criteria:
- Age ≥18 years
- Laboratory-confirmed SARS-CoV-2 infection within 3 days (of proposed consent) or the
presence of symptoms or signs providing a high probability of COVID-19 disease who
have symptoms within 7 days prior to diagnosis as determined by Infectious Disease
specialist or treating physicians.
- Outpatients. No previous hospitalization within the past 3 months.
- Subjects must have at least one of the following high-risk features for clinical
deterioration:
- Hypertension
- Diabetes mellitus
- Moderate to severe Chronic Obstructive Pulmonary Disease or asthma
- Cancer patients who have received any immunosuppressive drugs within a year from
enrollment.
- Obesity as defined by a body mass index > 30 kg/m2.
- Living in a nursing home or long-term facility
- Underlying serious heart condition as determined by the treating physician
- Immunocompromised subject as defined by the treating physician or by the
Infectious Disease specialist
- Ability to provide informed consent by the patient or healthcare proxy.
- Ability to return for repeated testing and observation to the hospital.
- Patients must have adequate organ and marrow function measured within the last 30
days as defined below:
- platelets ≥100,000
- aspartate transaminase or alanine transaminase ≤3 times institutional upper limit of
normal
- creatinine ≤ 1.5 times institutional upper limit of normal OR
- glomerular filtration rate ≥45 mL/min/1.73 m2 unless data exists supporting safe use
at lower kidney function values, no lower than 30 mL/min/1.73 m2
Exclusion Criteria:
- Severe COVID-19 is defined by one or more of the following:
- blood oxygen saturation ≤ 90%
- partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
- lung infiltrates ≥ 50% within 24 to 48 hours
- Life-threatening COVID-19 is defined as one or more of the following:
- respiratory failure
- septic shock
- multiple organ dysfunction or failure
- Weight less than 45 kg.
- Pregnant or breast-feeding females
- Subjects on dialysis or with creatinine clearance < 45 ml/min
- Subjects who need antiviral administration due to severe viral diseases other than
COVID-19, such as HIV, hepatitis B, and hepatitis C
- Existing Division of Microbiology and Infectious Disease Toxicity Scale for
determining the severity of adverse events grade 3 or greater.
- Uncontrolled seizure disorder
- Subjects with reflux esophagitis after chronic pancreatitis and gastrectomy surgery.
- Patients with reflux esophagitis after surgery.
- Known allergy to Artemisia annua or camostat mesilate.
- Currently receiving any study medications for other indications.
- Concurrent use of medication that would cause moderate or severe due to drug-drug
interactions with study medication.
Specifically:
- Patients receiving Artemisia annua tea may not be currently taking strong inducers of
CYP2A6, including phenobarbital and rifampin.
- Receipt in the 12 hours prior to enrollment, or planned administration during the
14-day study period that treating clinicians feel cannot be substituted for another
medication, of any of the following: amiodarone; cimetidine; dofetilide;
phenobarbital; phenytoin; or sotalol.
- Cancer patients receiving active immunosuppressive treatment cannot be enrolled unless
they are on a treatment holiday with no antineoplastic treatment with 3 weeks of
enrollment.
- Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency,
or glucose-galactose malabsorption
- Subjects who have a history of drug and/or alcohol abuse within 52 weeks before
screening
- Enrollment on other experimental therapies for COVID-19.
- Inability to receive enteral medications
- Patients with psychiatric illness/social situations that would limit compliance with
study requirements.
- Subjects who have a history of drug and/or alcohol abuse within 52 weeks before
screening
- Any other condition that in the opinion of the treating physician justifies exclusion
from the study.
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, None - Non-US/Canada, Mexico
Jose G Gotes Palazuelos, MD, Principal Investigator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran