COVID-19 Study of Safety and Tolerability of Alvelestat

NCT04539795 | Completed Phase 1 Results FDA Drug

• 1 other identifier: IRB-300005845
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

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

  Safety Outcome Assessment

  to day 60

Secondary Outcomes (5)

• 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 D-dimer

  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.

• Mortality Rate

  to Day 90

Study Arms (4)

Placebo oral tablet

PLACEBO COMPARATOR

placebo

Drug: Placebo

Alvelestat oral tablet - dose 1

ACTIVE COMPARATOR

MPH966

Drug: Alvelestat

Alvelestat oral tablet - dose 2

ACTIVE COMPARATOR

MPH966

Drug: Alvelestat

Alvelestat oral tablet - dose 3

ACTIVE COMPARATOR

MPH966

Drug: Alvelestat

Interventions

Alvelestat DRUG

oral tablet

Also known as: MPH966

Alvelestat oral tablet - dose 1; Alvelestat oral tablet - dose 2; Alvelestat oral tablet - dose 3

Placebo DRUG

oral tablet

Placebo oral tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients who have previously had a score of 6 or 7 on the WHO 9-point Ordinal Scale
• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Mereo BioPharma: collaborator

Study Sites (1)

UAB Lung Health Center

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Wells (Study PI)
• Organization: University of Alabama at Birmingham (UAB)

LungHealth@uabmc.edu

205-934-5555

Study Officials

• James M Wells, MD

  The University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 7, 2020
• Study Start: January 25, 2021
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: January 19, 2023
• Results First Posted: January 19, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)