SP16 as a Therapeutic for COVID-19 Induced ARDS

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled, Phase 1b study evaluates the safety and tolerability, and effects on cytokine and acute phase reactants of SP16, an anti-inflammatory drug, in patients with pneumonia due to SARS-CoV-2 infection. The study will enroll up to 20 patients and each eligible patient will be randomized to receive either one of two doses of SP16 (6 mg or 12 mg) or placebo by subcutaneous injection.

Detailed Description
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SARS-CoV-2 infection is associated with excessive inflammation and cytokine storm that can result in lung damage and potentially severe disease. SP16 is an anti-inflammatory and homeostatic drug that rebalances innate immune responses potentially resulting in mitigation of inflammation and lung damage without immunosuppressive effects. SP16's mechanism of action is through targeting LRP1, a receptor that regulates a variety of physiological processes that contribute to inflammation and tissue injury, particularly in the lung. The main objective of this study is to determine the safety and tolerability, and effects on inflammation of SP16 administered subcutaneously at a dose of 6 mg (0.1 mg/kg) or 12 mg (0.2 mg/kg). SP16 has previously been well tolerated in both healthy individuals and heart attack patients at a dose of 0.2 mg/kg. The study will also evaluate improvements in clinical parameters such as patients requiring ventilation, improvement in blood oxygen levels (as defined by both SpO2 > 95% and respiratory rate ≤ 20/minute) and duration of hospitalization or time spent in the Intensive Care Unit (ICU).

Official Title
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SP16 as a Therapeutic for SARS-CoV-2 Induced ARDS

Conditions
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Pneumonia, SARS CoV 2 Infection

Intervention / Treatment
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* Drug: SP16 (6mg)
* Other: Placebo
* Drug: SP16 (12 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be considered eligible to participate in this study, the subject must meet all of the Inclusion criteria listed below: Hospitalized patients age ≥ 18 with diagnosis of SARS-CoV-2-infection based on positive PCR test result and can provide informed consent Diagnosed with pneumonia due to SARS-CoV-2 Respiratory rate ≥ 25/minute and SpO2 ≤ 93% Review of Chest radiograph, chest computed tomography (CT) scan, or chest ultrasound consistent with bilateral infiltrates. Horowitz index (partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2]) ≤ 300. If a subject does not have an arterial line in place, a SpO2/FiO2 ≤ 315 may be used. Exclusion Criteria: To be eligible for entry into the study, the subject must not meet any of the exclusion criteria listed below: Age < 18 Pregnant or lactating women History of heart failure Clinically significant cardiac dysrhythmia, as determined by investigator History renal impairment Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2000 mm3, aspartate aminotransferase

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Cohort 1 - 7 subjects will be randomized to receive SP16 6 mg or placebo in a 7:3 ratio. Cohort 2 - 7 subject will be randomized to receive SP16 12 mg or placebo in a 7:3 ratio.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort dose 1 of SP16<br>Patients in cohort 1 (low dose SP16) will receive a single dose of SP16 (0.1 mg/kg or 6 mg) by subcutaneous injection | Drug: SP16 (6mg)<br>* SP16 will be administered as 2 concurrent, separate 2 mL s.c injections of 3mg/mL SP16<br>|
| Experimental: Cohort dose 2 of SP16<br>Patients in cohort 2 (high dose SP16) will receive a single dose of SP16 (0.2 mg/kg or 12 mg) by subcutaneous injection | Drug: SP16 (12 mg)<br>* SP16 will be administered as a single 2 mL s.c. injection of 3 mg/mL SP16 and 1 concurrent separate 2 mL s.c. injection of sterile water<br>|
| Placebo Comparator: Placebo<br>Patients in placebo arm will receive sterile water by subcutaneous injection. | Other: Placebo<br>* Placebo will be administered as 2 concurrent, separate 2 mL s.c. injections of sterile water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SP16 in subjects with pneumonia due to SARS-CoV-2 | Safety and tolerability of SP16 in subjects with pneumonia due to SARS-CoV-2 based on number of adverse events (AEs) | Day 1 to 14 | 
| Change in inflammatory cytokines | Subjects' change from baseline in plasma concentrations of inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8) | Day 3, Day 6, and Day 14 | 
| Change in acute phase reactants | Subjects' change from baseline of acute phase reactants (CRP, α-2 macroglobulin, fibrinogen, and D-dimer) | Day 3, Day 6, and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects requiring ventilation | The proportion of subjects in each dose group who required intubation and noninvasive ventilation by Day 14 | Day 14 | 
| Improvement from baseline in SpO2 | The proportion of subjects in each dose group who exhibited improvement from baseline in SpO2 levels, as defined by both SpO2 > 95% and respiratory rate ≤ 20/minute, at Days 3 and 14 | Days 3 and 14 | 
| Cumulative days on ventilator | Cumulative days on ventilator for each subject who required mechanical ventilation at any time during Day 1 to Day 14 period | Day 1 to 14 | 
| Duration of hospitalization | Subjects' duration of hospitalization over the Day1 to Day 14 period | Day 1 to 14 | 
| Time to clinical improvement | Subjects' time to clinical improvement (TTCI), which is defined as a National Early Warning Score 1 (NEWS2) of < 2 to be maintained for 24 h (during Days 1 to 14) | Day 1 to 14 | 
| Proportion of subjects experiencing TTCI | The proportions of subjects in each cohort who experienced TTCI, which is defined as NEWS2 of < 2 to be maintained for 24 h | Day 1 to 14 | 
| Subjects time to death | Subjects time to death or censoring over the period from Day 1 to Day 14 (subjects who withdraw prior to Day 14 will be censored on the day of withdrawal; subjects alive on Day 14 will be censored on Day 14) | Day 1 to 14 | 
| Change from baseline in Horowitz index | Subjects' change from baseline on Days 6 and 14 in Horowitz index or in SpO2/FiO2 | Days 6 and 14 | 
| Subject's cumulative days in ICU | Subjects' cumulative number of days spent in the Intensive Care Unit (ICU) over Days 1 to 14 | Day 1 to 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia due to SARS-CoV-2