COSTA: COVID-19 Study of Safety and Tolerability of Alvelestat

Sponsor
University of Alabama at Birmingham (Other)
Overall Status
Completed
CT.gov ID
NCT04539795
Collaborator
Mereo BioPharma (Industry)
15
Enrollment
1
Location
4
Arms
9.1
Actual Duration (Months)
1.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Jan 25, 2021
Actual Primary Completion Date :
Oct 29, 2021
Actual Study Completion Date :
Oct 29, 2021

Arms and Interventions

ArmIntervention/Treatment
Placebo Comparator: Placebo oral tablet

placebo

Drug: Placebo
oral tablet

Active Comparator: Alvelestat oral tablet - dose 1

MPH966

Drug: Alvelestat
oral tablet
Other Names:
  • MPH966
  • Active Comparator: Alvelestat oral tablet - dose 2

    MPH966

    Drug: Alvelestat
    oral tablet
    Other Names:
  • MPH966
  • Active Comparator: Alvelestat oral tablet - dose 3

    MPH966

    Drug: Alvelestat
    oral tablet
    Other Names:
  • MPH966
  • Outcome Measures

    Primary Outcome Measures

    1. Numbers and % of subjects who experience at least 1 treatment-emergent adverse event [to day 60]

      Safety Outcome Assessment

    2. Mortality rate [to Day 90]

    3. Adverse events of special interest [to Day 14 (acute treatment period) or EoT]

      clinically significant safety monitoring labs tests

    Secondary Outcome Measures

    1. Effect of alvelestat on blood pharmacodynamic biomarkers of inflammation [to day 10]

      neutrophil elastase

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1UAB Lung Health CenterBirminghamAlabamaUnited States35294

    Sponsors and Collaborators

    • University of Alabama at Birmingham
    • Mereo BioPharma

    Investigators

    • Principal Investigator: James M Wells, MD, The University of Alabama at Birmingham

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    James Michael Wells, Associate Professor, University of Alabama at Birmingham
    ClinicalTrials.gov Identifier:
    NCT04539795
    Other Study ID Numbers:
    • IRB-300005845
    First Posted:
    Sep 7, 2020
    Last Update Posted:
    Nov 18, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 18, 2021