SP16 as a Therapeutic for COVID-19 Induced ARDS

Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05135624
• Other study ID #: IRBHSR#210341
• Status: Terminated
• Phase: Phase 1
• Start date: December 1, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: May 2024
• Source: Serpin Pharma, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Pneumonia

Intervention

Drug:
• SP16 (6mg)
SP16 will be administered as 2 concurrent, separate 2 mL s.c injections of 3mg/mL SP16

Other:
• Placebo
Placebo will be administered as 2 concurrent, separate 2 mL s.c. injections of sterile water

Drug:
• SP16 (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

Locations

Country	Name	City	State
United States	UVA Health Center	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Serpin Pharma, LLC	University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Change in inflammatory cytokines	Subjects' change from baseline in plasma concentrations of inflammatory cytokines (IL-1ß, TNF-a, IL-6, and IL-8)	Day 3, Day 6, and Day 14
Primary	Change in acute phase reactants	Subjects' change from baseline of acute phase reactants (CRP, a-2 macroglobulin, fibrinogen, and D-dimer)	Day 3, Day 6, and Day 14
Secondary	Proportion of subjects requiring ventilation	The proportion of subjects in each dose group who required intubation and noninvasive ventilation by Day 14	Day 14
Secondary	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
Secondary	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
Secondary	Duration of hospitalization	Subjects' duration of hospitalization over the Day1 to Day 14 period	Day 1 to 14
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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