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COVID-19 Study of Safety and Tolerability of Alvelestat (COSTA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04539795
Recruitment Status : Recruiting
First Posted : September 7, 2020
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Mereo BioPharma
Information provided by (Responsible Party):
James Michael Wells, University of Alabama at Birmingham

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 disease Intervention/treatment Phase
Covid19 Drug: Alvelestat Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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)
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2021

Arm Intervention/treatment
Placebo Comparator: Placebo oral tablet
placebo
Drug: Placebo
oral tablet

Active Comparator: Alvelestat oral tablet - dose 1
MPH966
Drug: Alvelestat
oral tablet
Other Name: MPH966

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

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




Primary Outcome Measures :
  1. Numbers and % of subjects who experience at least 1 treatment-emergent adverse event [ Time Frame: to day 60 ]
    Safety Outcome Assessment

  2. Mortality rate [ Time Frame: to Day 90 ]
  3. Adverse events of special interest [ Time Frame: 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 [ Time Frame: to day 10 ]
    neutrophil elastase



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04539795


Contacts
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Contact: James M Wells, MD 205-934-5555 jmwells@uabmc.edu
Contact: Mark T Dransfield, MD 205-934-5555 mdransfield@uabmc.edu

Locations
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United States, Alabama
UAB Lung Health Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: James M Wells, MD    205-934-5555    jmwells@uabmc.edu   
Contact: Mark Dransfield, MD    205-934-5555    mdransfield@uabmc.edu   
Sponsors and Collaborators
University of Alabama at Birmingham
Mereo BioPharma
Investigators
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Principal Investigator: James M Wells, MD The University of Alabama at Birmingham
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Responsible Party: James Michael Wells, Associate Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04539795    
Other Study ID Numbers: IRB-300005845
First Posted: September 7, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No