SP16 as a Therapeutic for COVID-19 Induced ARDS

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pneumonia; SARS CoV 2 Infection
• Intervention / Treatment: Drug: SP16 (6mg); Drug: SP16 (12 mg); Other: Placebo

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).

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Roselove Asare; Phone Number: 4342436074; Email: rnn3b@virginia.edu
• Study Contact Backup: Name: Halle Raisigel; Phone Number: 5712281708; Email: halle@serpinpharma.com

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • UVA Health Center
      • Contact: Roselove Asare; Phone Number: 434-243-6074; Email: rnn3b@virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort dose 1 of SP16; 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); SP16 will be administered as 2 concurrent, separate 2 mL s.c injections of 3mg/mL SP16
Experimental: Cohort dose 2 of SP16; 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); 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
Placebo Comparator: Placebo; Patients in placebo arm will receive sterile water by subcutaneous injection.	Other: Placebo; Placebo will be administered as 2 concurrent, separate 2 mL s.c. injections of sterile water

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Serpin Pharma, LLC
• Collaborators: University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 17, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Pneumonia due to SARS-CoV-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: IRBHSR#210341

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No