Safety and Tolerability Study of IV ST266 in COVID-19 Subjects

Study Overview
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Brief Summary
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The primary aim of the study is to evaluate the safety and tolerability of open-label ST266 given to subjects with confirmed COVID-19 infection through IV administration once a day of 5 consecutive days.

Detailed Description
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This clinical trial will utilize a 3+3 enrollment design with sentinel approach.

Official Title
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A Phase 1, Multi-Center, Open-Label, Safety and Tolerability Study of Intravenous Administration of ST266 in Subjects With Confirmed COVID-19 Infection

Conditions
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Cytokine Release Syndrome

Intervention / Treatment
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* Biological: ST266


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant/non-breastfeeding females age 18-70 years of age. Laboratory confirmed SARS-CoV-2 infection determined by PCR or other commercial/public health assay (test results must be obtained within 7-days of the Screening Visit). BMI between 18 and 39 inclusive, with a maximum weight of 150 kg (330lbs). Asymptomatic or mildly symptomatic COVID-19 positive subject with a score of 1 or 2 on the WHO 7-point ordinal scale. Subjects with pulse oximetry of > 94% on room air Subjects have controlled blood pressure of < 160/100 mmHg or systolic BP > 90 mmHg (or 20 mmHg less than usual range, whichever is higher) Subjects with pulse < 120 bpm Willingness and ability to comply with study-related procedures and assessments. If female, subjects must use an effective method of birth control or abstain from sexual relations with a male partner (unless has undergone tubal ligation or is 1 year postmenopausal) for their duration of study participation. If male, subjects must use an effective method of birth control or abstain from sexual relations with a female partner (unless has undergone a vasectomy and it has been more than 6 months) for their duration of study participation. Subject or subject's legal representative provides written consent prior to the initiation of any Screening or study specific procedures. Exclusion Criteria: Subjects requiring immediate admission to the hospital due to complications of COVID-19 infection. Subject has an untreated active bacterial, fungal, viral or other infection not related to COVID-19 infection. Subjects with chronic lung diseases of any etiology including idiopathic pulmonary fibrosis, Tuberculosis, COPD, persistent asthma, and pulmonary hypertension. Subjects with a severe history of cardiac disease (such as congestive heart failure, coronary artery disease, cardiac arrhythmia) Subjects with a history of neurological disorders (such as epilepsy, stroke, encephalopathy, Guillain-Barré syndrome) Subjects with D-dimer > 2 ug/mL Subjects with a history of coagulopathy or currently taking anti-coagulation medication Subjects with PTT ≥ 100s or INR ≥ 2.75 Malignancy in the last 5 years (except successfully treated basal cell carcinoma). Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR < 30). Subjects with a reactive or positive screening test result For Hepatitis A virus immunoglobulin M (HAV IgM), Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus Antibody (HCVAb) or Human Immunodeficiency Virus Antibody (HIVAb). TBIL> 2×ULN, ALT > 3×ULN, AST> 3×ULN, or ALP> 3×ULN. Neutrophils <1000/mm3, PLT<50×10^9/L, or HGB<8g/dL Previous participation in any other interventional clinical trial for the treatment for COVID-19. Subject actively participating in any other clinical study (with the exception of observational studies where there is no intervention with an investigational product or device) Use of anti-cancer or immunomodulatory biological drug or kinase inhibitor (e.g., tocilizumab, sarilumab) or, JAK inhibitors (within 30 days of enrollment or five times the half-life [whichever is longer]). Chronic glucocorticosteroid use equivalent to daily oral prednisone > 10 mg per day (10 mg oral prednisone every other day is allowed). Live (live-attenuated) vaccines are not permitted within 2 weeks prior to enrollment or during the study treatment and safety follow-up periods, including the SARS-CoV-2 vaccine (with the exception of the Flu vaccine which is allowed at any time) Subject is pregnant or breastfeeding or plans to become pregnant within 12 months. Subjects with a history of alcohol or drug abuse, or the use of illicit drugs within the 12 months prior to Screening or use of medical marijuana within 1 month prior to Screening. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>0.1 ml/kg IV ST266 once a day for 5 days | Biological: ST266<br>* 1X ST266<br>|
| Experimental: Cohort 2<br>0.25 ml/kg IV ST266 once a day for 5 days | Biological: ST266<br>* 1X ST266<br>|
| Experimental: Cohort 3<br>0.5 ml/kg IV ST266 once a day for 5 days | Biological: ST266<br>* 1X ST266<br>|
| Experimental: Cohort 4<br>1.0 ml/kg IV ST266 once a day for 5 days | Biological: ST266<br>* 1X ST266<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Treatment-Emergent Adverse Events | Determine the incidence and severity of treatment-emergent adverse events related to the IV administration of ST266 based on findings from physical examinations, laboratory evaluations, vital signs, and ECG measurements. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulse Oximetry | Percent improvement in pulse oximetry from Baseline to Day 14 | 14 days | 
| Fever | Time to resolution of fever | 14 days | 
| Clinical Status on Ordinal Scale | Improvement or absence of worsening in clinical status on WHO 7-point ordinal scale from baseline to Day 14 | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19