Clinical Trials/NCT04539795

NCT04539795

Completed

Phase 1

A Phase Ib/II, Single Center, Placebo-Controlled, Randomized, Blinded Study in Adult Patients (> 18 Years) With COVID-19 Respiratory Disease, to Evaluate, Safety, Tolerability and Mechanistic Effect of Alvelestat on Top of Standard of Care (COSTA)

University of Alabama at Birmingham1 site in 1 country15 target enrollmentJanuary 25, 2021

ConditionsCovid19

InterventionsAlvelestat Placebo

DrugsAlvelestat Placebo

Overview

Phase: Phase 1
Intervention: Alvelestat
Conditions: Covid19
Sponsor: University of Alabama at Birmingham
Enrollment: 15
Locations: 1
Primary Endpoint: Numbers and % of Subjects Who Experience at Least 1 Treatment-emergent Adverse Event
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety, tolerability and pharmacokinetics (PK), and explore the mechanistic and clinical effect of alvelestat (an oral neutrophil elastase inhibitor) orally twice per day for 10 days added to standard of care in adult patients (≥18 years) with COVID-19 respiratory disease.

Registry

clinicaltrials.gov

Start Date

January 25, 2021

End Date

October 29, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of Alabama at Birmingham

Responsible Party

Principal Investigator

James Michael Wells

Associate Professor

University of Alabama at Birmingham

Eligibility Criteria

Inclusion Criteria

•Male or Female
•Age ≥18 years
•Proven SARS-Cov-2 infection (confirmed by PCR from a nasopharyngeal or lower respiratory tract sample)
•A score of Grade 3 to 5 on the WHO 9-point Ordinal Scale
•Male participants must agree to use a highly effective contraception during the treatment period and for at least 4 days after the last dose of study treatment and refrain from donating sperm during this period.
•Female participants are eligible to participate if not pregnant; not breastfeeding; and at least one of the following conditions is met:
•Not a woman of childbearing potential OR A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment phase and for at least 4 days after the last dose of study medication - Capable of giving signed informed consent which includes a commitment to comply with the requirements and restrictions listed in the informed consent form (ICF) and within this protocol.

Exclusion Criteria

•Patients who have previously had a score of 6 or 7 on the WHO 9-point Ordinal Scale
•Patients who require support with invasive mechanical ventilation at the time of inclusion, or expected to be required within 24 hours of randomization
•Alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) \>2 × the upper limit of normal (ULN) OR Total Bilirubin \> ULN. In patients with a documented history of Gilbert's Syndrome AND baseline total bilirubin elevation consistent with an exacerbation of Gilbert's Syndrome (i.e. no other cause of total bilirubin elevation), subjects may enroll if total bilirubin is \< 5x ULN.
•Diagnosis of liver cirrhosis, esophageal varices, ascites or hepatic encephalopathy
•Chronic liver diseases such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, haemochromatosis
•Significant renal disease or infection (as determined by the Investigator) including stage 4 chronic kidney disease or estimated glomerular filtration rate \<60mL/min
•Absolute neutrophil count ≤ 1000/µL at screening
•Myocardial infarction, transient ischemic attack or stroke within 3 months prior to the first dose
•Current unstable angina or congestive heart failure (New York Heart Association III/IV)
•Screening 12-lead EKG with a measurable QTc interval according to Fridericia correction (QTcF) \>450 ms

Arms & Interventions

Alvelestat oral tablet - dose 3

MPH966

Intervention: Alvelestat

Placebo oral tablet

placebo

Intervention: Placebo

Alvelestat oral tablet - dose 1

MPH966

Intervention: Alvelestat

Alvelestat oral tablet - dose 2

MPH966

Intervention: Alvelestat

Outcomes

Primary Outcomes

Numbers and % of Subjects Who Experience at Least 1 Treatment-emergent Adverse Event

Time Frame: to day 60

Safety Outcome Assessment

Secondary Outcomes

Mortality Rate(to Day 90)
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of D-dimer(Randomization through Day 10 or hospital discharge, whichever was shorter.)
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of NETosis(Randomization through Day 10 or hospital discharge, whichever was shorter.)
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of Inflammation(Randomization through Day 10 or hospital discharge, whichever was shorter.)
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of Desmosine(Randomization through Day 10 or hospital discharge, whichever was shorter.)