Pneumonia, SARS CoV 2 Infection
Conditions
Keywords
Pneumonia due to SARS-CoV-2
Brief summary
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
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).
Interventions
DRUGSP16 (6mg)
SP16 will be administered as 2 concurrent, separate 2 mL s.c injections of 3mg/mL SP16
OTHERPlacebo
Placebo will be administered as 2 concurrent, separate 2 mL s.c. injections of sterile water
DRUGSP16 (12 mg)
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
Sponsors
Serpin Pharma, LLC
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of SP16 in subjects with pneumonia due to SARS-CoV-2 | Day 1 to 14 | Safety and tolerability of SP16 in subjects with pneumonia due to SARS-CoV-2 based on number of adverse events (AEs) |
| Change in inflammatory cytokines | Day 3, Day 6, and Day 14 | Subjects' change from baseline in plasma concentrations of inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8) |
| Change in acute phase reactants | Day 3, Day 6, and Day 14 | Subjects' change from baseline of acute phase reactants (CRP, α-2 macroglobulin, fibrinogen, and D-dimer) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of hospitalization | Day 1 to 14 | Subjects' duration of hospitalization over the Day1 to Day 14 period |
| Time to clinical improvement | Day 1 to 14 | 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) |
| Proportion of subjects experiencing TTCI | Day 1 to 14 | The proportions of subjects in each cohort who experienced TTCI, which is defined as NEWS2 of \< 2 to be maintained for 24 h |
| Proportion of subjects requiring ventilation | Day 14 | The proportion of subjects in each dose group who required intubation and noninvasive ventilation by Day 14 |
| Change from baseline in Horowitz index | Days 6 and 14 | Subjects' change from baseline on Days 6 and 14 in Horowitz index or in SpO2/FiO2 |
| Subject's cumulative days in ICU | Day 1 to 14 | Subjects' cumulative number of days spent in the Intensive Care Unit (ICU) over Days 1 to 14 |
| Subjects time to death | Day 1 to 14 | 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) |
| Improvement from baseline in SpO2 | Days 3 and 14 | 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 |
| Cumulative days on ventilator | Day 1 to 14 | Cumulative days on ventilator for each subject who required mechanical ventilation at any time during Day 1 to Day 14 period |
Countries
United States
Outcome results
None listed