COVID-19 Study of Safety and Tolerability of Alvelestat

NCT ID: NCT04539795

Last Updated: 2023-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-25
• Study Completion Date: 2021-10-29

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo oral tablet

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral tablet

Alvelestat oral tablet - dose 1

MPH966

Group Type: ACTIVE_COMPARATOR

Alvelestat

Intervention Type: DRUG

oral tablet

Alvelestat oral tablet - dose 2

MPH966

Group Type: ACTIVE_COMPARATOR

Alvelestat

Intervention Type: DRUG

oral tablet

Alvelestat oral tablet - dose 3

MPH966

Group Type: ACTIVE_COMPARATOR

Alvelestat

Intervention Type: DRUG

oral tablet

Interventions

Alvelestat

oral tablet

Intervention Type: DRUG

Placebo

oral tablet

Intervention Type: DRUG

Other Intervention Names

MPH966

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
• Anticipated transfer to another hospital that is not the study center within 24 hours
• Allergy to study medication or excipients
• Inability to swallow tablets
• Other documented comorbidities or laboratory abnormalities that in the opinion of the Investigator could affect the outcome of the study assessments, participant safety, or ability of the participant to comply with the requirements of the protocol
• Any patient whose interests are not best served by study participation, as determined by the Investigator

Excluded Prior/Concomitant Therapy

• Requirement for medications mainly metabolized by CYP2C9 and with narrow therapeutic index (eg, warfarin, phenytoin) is prohibited unless therapeutic monitoring available for duration of alvelestat dosing
• Medicines that are potent CYP3A4 inhibitors including (but are not limited to) clarithromycin, diltiazem, erythromycin, itraconazole, ketoconazole, ritonavir, verapamil and potent inducers including but not limited to phenobarbital, phenytoin and rifampicin, will be exclusionary
• Requirement for medications substantially reliant on OATP1B1 for metabolism where discontinuation during study drug administration is not possible or where fluctuations in levels are considered clinically important (as per investigator judgement) and cannot be clinically monitored (e.g., statins, valsartan, olmesartan, enalapril, repaglinide)

Excluded Prior/Concurrent Clinical Study Experience

• Participation in any clinical investigation using investigational treatments within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initial dosing (or longer if required by local regulations) is prohibited. Use of remdesivir (Veklury) under the conditions of the authorization for emergency use in the US, and per manufacturer's instructions, is permitted.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mereo BioPharma

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

James Michael Wells

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James M Wells, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Alabama at Birmingham

Locations

UAB Lung Health Center

Birmingham, Alabama, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IRB-300005845

Identifier Type: -

Identifier Source: org_study_id