Covid19Phase 1/2COSTANCT04539795
COVID-19 Study of Safety and Tolerability of Alvelestat
A Phase 1/2 study testing Alvelestat in people with Covid19, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Alvelestat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jan 2021to 29 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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
- Being tested
- Alvelestat, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlvelestatDrug
Also called MPH966
oral tablet
PlaceboDrug
oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Placebo oral tablet | Placebo comparator | placebo Receives: Drug: Placebo |
| Alvelestat oral tablet - dose 1 | Active comparator | MPH966 Receives: Drug: Alvelestat |
| Alvelestat oral tablet - dose 2 | Active comparator | MPH966 Receives: Drug: Alvelestat |
| Alvelestat oral tablet - dose 3 | Active comparator | MPH966 Receives: Drug: Alvelestat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers and % of Subjects Who Experience at Least 1 Treatment-emergent Adverse Event
Safety Outcome Assessment
Measured: to day 60
Secondary outcomes (5)
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of NETosis
Change in blood markers of NETosis
Measured: Randomization through Day 10 or hospital discharge, whichever was shorter.
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of Inflammation
Change in blood markers of inflammation
Measured: Randomization through Day 10 or hospital discharge, whichever was shorter.
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of D-dimer
Change in blood markers of d-dimer
Measured: Randomization through Day 10 or hospital discharge, whichever was shorter.
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of Desmosine
Change in blood markers of desmosine
Measured: Randomization through Day 10 or hospital discharge, whichever was shorter.
Mortality Rate
Measured: to Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2020
- Study start25 Jan 2021
- Primary completion29 Oct 2021
- Study completion29 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Mereo BioPharma
- Responsible party
- Principal investigator, James Michael Wells, University of Alabama at Birmingham
- Investigators
- James M Wells, MD, Principal investigator, The University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04539795
- Sponsor's protocol ID
- IRB-300005845
- Acronym
- COSTA
- Status last verified
- Dec 2022
- First submitted
- 3 Sep 2020
- Last updated
- 19 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04539795
- Acronym / sponsor ID
- COSTA / IRB-300005845
- Conditions
- Covid19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Mereo BioPharma
- Study start
- 25 Jan 2021 (actual)
- Primary completion
- 29 Oct 2021 (actual)
- Study completion
- 29 Oct 2021 (actual)
- First posted
- 7 Sep 2020 (actual)
- Results
- Posted 19 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo oral tablet | Placebo comparator | Drug: Placeboplacebo |
| Alvelestat oral tablet - dose 1 | Active comparator | Drug: AlvelestatMPH966 |
| Alvelestat oral tablet - dose 2 | Active comparator | Drug: AlvelestatMPH966 |
| Alvelestat oral tablet - dose 3 | Active comparator | Drug: AlvelestatMPH966 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlvelestatAlso: MPH966oral tablet | Drug | Alvelestat oral tablet - dose 1, Alvelestat oral tablet - dose 2, Alvelestat oral tablet - dose 3 |
| Placebooral tablet | Drug | Placebo oral tablet |
Primary outcome
Numbers and % of Subjects Who Experience at Least 1 Treatment-emergent Adverse Event
Time frame: to day 60
Safety Outcome Assessment
5 secondary outcomes
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of NETosis
Time frame: Randomization through Day 10 or hospital discharge, whichever was shorter.
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of Inflammation
Time frame: Randomization through Day 10 or hospital discharge, whichever was shorter.
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of D-dimer
Time frame: Randomization through Day 10 or hospital discharge, whichever was shorter.
Effect of Alvelestat on Blood Pharmacodynamic Biomarkers of Desmosine
Time frame: Randomization through Day 10 or hospital discharge, whichever was shorter.
Mortality Rate
Time frame: to Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James M Wells, MD principal investigator
The University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Alvelestat in people with Covid19, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numbers and % of Subjects Who Experience at Least 1 Treatment-emergent Adverse Event (time frame: to day 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2023.