This study is currently recruiting participants.
Number
000134-I
Sponsoring Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Non-English Speaking;Children
Keywords
viral RNA; viral antigen assay; mid-turbinate swab specimen; Quantitative reverse transcriptase polymerase chain reaction; Severe Acute Respiratory Syndrome Coronavirus 2
Recruitment Keyword(s)
None
Condition(s)
SARS-Co V-2 infection
Investigational Drug(s)
Zotatifin (Intravenous formulation); eFT226
Investigational Device(s)
Intervention(s)
Drug: Zotatifin Other: Placebo
Supporting Site
National Institute of Allergy and Infectious Diseases
COVID-19 is an infection in the lungs and respiratory tract. It causes symptoms such as fever, coughing, fatigue, and trouble breathing. Some people have mild symptoms. But for others, COVID-19 can cause life-threatening complications. There are no cures for COVID-19. Researchers want to see if a new drug can help.
Objective:
To investigate the safety, tolerability, and potential benefit of zotatifin to treat COVID-19.
Eligibility:
English-speaking adults ages 18-65 who have been diagnosed with mild or moderate COVID-19.
Design:
Participants will be screened with the following:
Medical history
Medicine review
Physical exam
Heart, lung, and stomach assessments
Chest X-ray
Blood and urine samples
Electrocardiogram to see how well their heart is working
COVID-19 test, if needed.
Some screening tests will be repeated during the study.
Participants will attend all study visits as outpatient clinic visits at the NIH Clinical Center. They will get intravenous (IV) infusions of the study drug or placebo. For this, a small tube is placed into an arm vein. They will also have an IV line placed in an arm vein to draw blood.
Participants will give a deep nasal swab sample.
Participants will give a saliva sample and a front nasal sample. They will be trained on how to collect these samples at home.
Participants will keep a diary. It is a paper questionnaire that asks about their COVID-19 symptoms.
Participation in this study will last approximately 5-6 weeks and will include 7 study visits to the NIH Clinical Center and 1 follow-up telephone call.
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INCLUSION CRITERIA: Patients who meet all of the following criteria will be eligible to participate in the study: -Has provided informed consent and any authorizations required by local law; -Is a male or female patient greater than or equal to 18 and <65 years of age; -Has a laboratory-documented positive test for SARS-CoV-2 infection as determined by local laboratory using a standard, Food and Drug Administration (FDA) -approved reverse transcriptase polymerase chain reaction (RT-PCR) or viral antigen assay from any oral or respiratory sample collected within 7 days of randomization; Note: The first documented positive test for SARS-CoV-2 must be within 7 days of randomization. -Has at least 1 symptoms associated with COVID-19 (eg, fever or chills, cough, shortness of breath or difficulty breathing on exertion, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea), defined as the following: --Mild COVID-19 ---Positive testing by standard reverse (RT-PCR) assay or viral antigen assay or equivalent test; ---Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea; and ---No clinical signs indicative of moderate, severe, or critical severity; --Moderate COVID-19 ---Positive testing by standard RT-PCR assay or viral antigen assay or equivalent testing; ---Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion; ---Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate greater than or equal to 20 breaths per minute, saturation of oxygen (SpO2) >93% on room air at sea level, heart rate greater than or equal to 90 beats per minute; and ---No clinical signs indicative of severe or critical severity; -Has adequate hepatic function during screening, defined as the following: --Serum alanine aminotransferase less than or equal to 3 (SqrRoot) upper limit of normal (ULN); --Serum aspartate aminotransferase less than or equal to 3 (SqrRoot) ULN; and --Serum bilirubin (total) less than or equal to 1.5 (SqrRoot) ULN (unless due to Gilbert s syndrome or hemolysis); -Has adequate bone marrow function during screening, defined as the following: --Absolute neutrophil count greater than or equal to 1.0 (SqrRoot) 10^9/L; --Platelet count greater than or equal to 100 (SqrRoot) 10^9/L; and Note: The Medical Monitor should be consulted for patients with platelet counts below the lower limit of normal. --Hemoglobin greater than or equal to 100 g/L (10.0 g/dL or 6.2 mmol/L); -Has adequate renal function during screening, defined as measured or estimated glomerular filtration rate greater than or equal to 60 mL/min, calculated by the Cockcroft-Gault formula using actual body weight; -Female patients of childbearing potential must meet all of the following criteria: --Is not pregnant (confirmed via a negative urine pregnancy test); --Is not breastfeeding; and --Is willing to use a protocol-recommended method of contraception or willing to abstain from heterosexual intercourse from the start of blinded study drug (zotatifin or placebo) until at least 90 days after administration of blinded study drug (zotatifin or placebo); Note: A female patient is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range and a negative serum or urine beta-human chorionic gonadotropin); or is menopausal (age greater than or equal to 55 years with amenorrhea for greater than or equal to 6 months). Male patients who can father a child must meet all of the following criteria: --Is willing to use a protocol-recommended method of contraception or willing to abstain from heterosexual intercourse with females of childbearing potential from the start of blinded study drug (zotatifin or placebo) until at least 90 days after administration of blinded study drug (zotatifin or placebo); and --Is willing to refrain from sperm donation from the start of blinded study drug (zotatifin or placebo) until at least 90 days after administration of blinded study drug (zotatifin or placebo); Note: A male patient is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. -Is willing to comply with the scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions; and Note: Psychological, social, familial, or geographical factors that may preclude adequate study participation should be considered. -In the judgment of the Investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the patient s disease. EXCLUSION CRITERIA: Patients who meet any of the following criteria will be excluded from participation in the study: -Is hospitalized for COVID-19; -Has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure; -Has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; greater than or equal to Grade 3 hypertension (diastolic blood pressure greater than or equal to 100 mmHg or systolic blood pressure greater than or equal to 160 mmHg); or history of congenital prolonged QT syndrome; -Has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening; Note: Maintenance therapy with inhaled corticosteroids with or without beta-2-agonist inhaler is allowed. -Has evidence of an ongoing or systemic bacterial, fungal, or viral infection other than SARS-CoV-2 infection, or history of incompletely treated tuberculosis (TB) and/or suspected or known extrapulmonary TB; Note: Patients meeting all other entry criteria may be randomized pending testing. If testing confirms any of these infections after randomization, the patient will be early terminated, followed for safety assessments, and should be discussed with the Medical Monitor. Patients with localized fungal infections of the skin or nails are eligible. Patients may be receiving topical antifungals. Systemic administration of azole antifungals is prohibited. -Has significant infiltrates (involving >50% of lung parenchyma) on chest X-ray within 1 week of screening; -Has known significant electrocardiogram (ECG) abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (AV) block type II, third-degree AV block, greater than or equal to Grade 2 bradycardia, or QTcF >450 msec for men or >470 msec for women; -Has a body mass index >35 kg/m2; -Has received a live vaccine within 30 days prior to randomization or COVID-19 vaccine <=7 days prior to randomization; Note: Patients vaccinated with the Janssen COVID-19 vaccine (Johnson & Johnson) or the adenoviral vector COVID-19 vaccines must have received the vaccine 30 days prior to randomization. Patients vaccinated for COVID-19 with other vaccines <=7 days prior to randomization may be considered following discussion with the Medical Monitor. -Has had major surgery within 4 weeks (inclusive) prior to randomization; -Has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type); -Has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system; -Has ongoing immunosuppressive therapy Note: At screening and during study participation, patients may be using systemic corticosteroids (doses less than or equal to 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. -Has ongoing use of a therapeutic anticoagulant or history of bleeding disorder; -Has ongoing use or plans to use experimental antivirals against SARS-CoV-2 during study participation; Note: Standard of care therapies that have undergone peer review for the treatment of COVID-19 are permitted. Please see the treatment guidelines by the Infectious Diseases Society of America (IDSA) for further detail. -Has used a moderate or strong inhibitor of CYP3A4 within 2 days prior to randomization, has used a strong or moderate inducer of cytochrome P450 (CYP)3A4 within 7 days prior to randomization or is expected to require use of a moderate or strong CYP3A4 inhibitor or inducer during study participation; -Has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study; Note: Participation in observational studies is allowed. -Has a known history of HIV or active hepatitis B virus, or active hepatitis C virus infection Note: Patients who verbally report no history of HIV, active hepatitis B virus, or an active hepatitis C infection during screening and meet all other study criteria will be permitted to randomize pending virology testing. Should virology results confirm HIV, active hepatitis B virus, or active hepatitis C virus infection, the patient may be early terminated from the study after discussion with the Medical Monitor and followed for safety assessments. -Has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo; -Has a recent history of drug abuse or use of narcotics that in the opinion of the Investigator will preclude study compliance; or; Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient s ability to provide informed consent, adversely affect the patient s ability to cooperate and participate in the study, or compromise the interpretation of study results.
Patients who meet all of the following criteria will be eligible to participate in the study:
-Has provided informed consent and any authorizations required by local law;
-Is a male or female patient greater than or equal to 18 and <65 years of age;
-Has a laboratory-documented positive test for SARS-CoV-2 infection as determined by local laboratory using a standard, Food and Drug Administration (FDA) -approved reverse transcriptase polymerase chain reaction (RT-PCR) or viral antigen assay from any oral or respiratory sample collected within 7 days of randomization;
Note: The first documented positive test for SARS-CoV-2 must be within 7 days of
randomization.
-Has at least 1 symptoms associated with COVID-19 (eg, fever or chills, cough, shortness of breath or difficulty breathing on exertion, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea), defined as the following:
--Mild COVID-19
---Positive testing by standard reverse (RT-PCR) assay or viral antigen assay or equivalent test;
---Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea; and
---No clinical signs indicative of moderate, severe, or critical severity;
--Moderate COVID-19
---Positive testing by standard RT-PCR assay or viral antigen assay or equivalent testing;
---Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion;
---Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate
greater than or equal to 20 breaths per minute, saturation of oxygen (SpO2) >93% on room air at sea level, heart rate greater than or equal to 90 beats per minute; and
---No clinical signs indicative of severe or critical severity;
-Has adequate hepatic function during screening, defined as the following:
--Serum alanine aminotransferase less than or equal to 3 (SqrRoot) upper limit of normal (ULN);
--Serum aspartate aminotransferase less than or equal to 3 (SqrRoot) ULN; and
--Serum bilirubin (total) less than or equal to 1.5 (SqrRoot) ULN (unless due to Gilbert s syndrome or hemolysis);
-Has adequate bone marrow function during screening, defined as the following:
--Absolute neutrophil count greater than or equal to 1.0 (SqrRoot) 10^9/L;
--Platelet count greater than or equal to 100 (SqrRoot) 10^9/L; and
Note: The Medical Monitor should be consulted for patients with platelet counts below the lower limit of normal.
--Hemoglobin greater than or equal to 100 g/L (10.0 g/dL or 6.2 mmol/L);
-Has adequate renal function during screening, defined as measured or estimated glomerular filtration rate greater than or equal to 60 mL/min, calculated by the Cockcroft-Gault formula using actual body weight;
-Female patients of childbearing potential must meet all of the following criteria:
--Is not pregnant (confirmed via a negative urine pregnancy test);
--Is not breastfeeding; and
--Is willing to use a protocol-recommended method of contraception or willing to abstain from heterosexual intercourse from the start of blinded study drug (zotatifin or placebo) until at least 90 days after administration of blinded study drug (zotatifin or placebo);
Note: A female patient is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range and a negative serum or urine beta-human chorionic gonadotropin); or is menopausal (age greater than or equal to 55 years with amenorrhea for greater than or equal to 6 months).
Male patients who can father a child must meet all of the following criteria:
--Is willing to use a protocol-recommended method of contraception or willing to abstain from heterosexual intercourse with females of childbearing potential from the start of blinded study drug (zotatifin or placebo) until at least 90 days after administration of blinded study drug (zotatifin or placebo); and
--Is willing to refrain from sperm donation from the start of blinded study drug (zotatifin or placebo) until at least 90 days after administration of blinded study drug (zotatifin or placebo);
Note: A male patient is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
-Is willing to comply with the scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions; and
Note: Psychological, social, familial, or geographical factors that may preclude adequate study participation should be considered.
-In the judgment of the Investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the patient s disease.
EXCLUSION CRITERIA:
Patients who meet any of the following criteria will be excluded from participation in the study:
-Is hospitalized for COVID-19;
-Has dyspnea at rest or while talking, or has signs and symptoms of overt or impending respiratory failure;
-Has significant cardiovascular disease, defined by myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; greater than or equal to Grade 3 hypertension (diastolic blood pressure greater than or equal to 100 mmHg or systolic blood pressure greater than or equal to 160 mmHg); or history of congenital prolonged QT syndrome;
-Has a history of chronic obstructive pulmonary disease or bronchial asthma requiring continuous treatment and/or intermittent or continuous oxygen within the 90 days prior to screening;
Note: Maintenance therapy with inhaled corticosteroids with or without beta-2-agonist inhaler is allowed.
-Has evidence of an ongoing or systemic bacterial, fungal, or viral infection other than SARS-CoV-2 infection, or history of incompletely treated tuberculosis (TB) and/or suspected or known extrapulmonary TB;
Note: Patients meeting all other entry criteria may be randomized pending testing. If testing confirms any of these infections after randomization, the patient will be early terminated, followed for safety assessments, and should be discussed with the Medical Monitor.
Patients with localized fungal infections of the skin or nails are eligible. Patients may be receiving topical antifungals. Systemic administration of azole antifungals is prohibited.
-Has significant infiltrates (involving >50% of lung parenchyma) on chest X-ray within 1 week of screening;
-Has known significant electrocardiogram (ECG) abnormalities at screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (AV) block type II, third-degree AV block, greater than or equal to Grade 2 bradycardia, or QTcF >450 msec for men or >470 msec for women;
-Has a body mass index >35 kg/m2;
-Has received a live vaccine within 30 days prior to randomization or COVID-19 vaccine <=7 days prior to randomization;
Note: Patients vaccinated with the Janssen COVID-19 vaccine (Johnson & Johnson) or the adenoviral vector COVID-19 vaccines must have received the vaccine 30 days prior to randomization. Patients vaccinated for COVID-19 with other vaccines <=7 days prior to randomization may be considered following discussion with the Medical Monitor.
-Has had major surgery within 4 weeks (inclusive) prior to randomization;
-Has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 2 years, completely resected basal cell and squamous cell carcinoma of the skin, and completely resected carcinoma in situ of any type);
-Has a history of or active uncontrolled systemic or local autoimmune disorders or other conditions that might impair or compromise the immune system;
-Has ongoing immunosuppressive therapy
Note: At screening and during study participation, patients may be using systemic corticosteroids (doses less than or equal to 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids.
-Has ongoing use of a therapeutic anticoagulant or history of bleeding disorder;
-Has ongoing use or plans to use experimental antivirals against SARS-CoV-2 during study participation;
Note: Standard of care therapies that have undergone peer review for the treatment of COVID-19 are permitted. Please see the treatment guidelines by the Infectious Diseases Society of America (IDSA) for further detail.
-Has used a moderate or strong inhibitor of CYP3A4 within 2 days prior to randomization, has used a strong or moderate inducer of cytochrome P450 (CYP)3A4 within 7 days prior to randomization or is expected to require use of a moderate or strong CYP3A4 inhibitor or inducer during study participation;
-Has previously received investigational product in a clinical study within 30 days or within 5 elimination half-lives (whichever is shorter) prior to randomization or is planning to take part in another therapeutic clinical study while participating in this study;
Note: Participation in observational studies is allowed.
-Has a known history of HIV or active hepatitis B virus, or active hepatitis C virus infection
Note: Patients who verbally report no history of HIV, active hepatitis B virus, or an active hepatitis C infection during screening and meet all other study criteria will be permitted to randomize pending virology testing. Should virology results confirm HIV, active hepatitis B virus, or active hepatitis C virus infection, the patient may be early terminated from the study after discussion with the Medical Monitor and followed for safety assessments.
-Has a known serious allergic reaction or hypersensitivity to components of zotatifin or placebo;
-Has a recent history of drug abuse or use of narcotics that in the opinion of the Investigator will preclude study compliance; or; Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient s ability to provide informed consent, adversely affect the patient s ability to cooperate and participate in the study, or compromise the interpretation of study results.
Principal Investigator
Referral Contact
For more information: