COVID-19Phase 2NCT04463004
Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation
A Phase 2 study testing Mavrilimumab in people with COVID-19 and Sars-CoV2, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Mavrilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2020to 30 Nov 2020
- Phase
- Phase 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
- Written informed consent must be obtained before any assessment is performed
- Documented COVID19 pneumonia defined as positive SARS-CoV2 test AND abnormalities/ infiltrates on chest x-ray or computed tomography AND active fever or documented fever within 24-48 hours or ongoing anti-pyretic use to suppress fever
- Hypoxia (Room air SpO2 <92% or requirement for supplemental oxygen)
- Increased serum inflammatory marker (CRP > 5 mg/dL)
- Severity of disease warrants inpatient hospitalization
Who cannot join
- Onset of COVID-19 symptoms >14 days
- Age < 18 years-old
- Hospitalized >7 days
- Mechanically ventilated
- Serious concomitant illness which in the opinion of the investigator precludes the patient from enrolling in the trial, including (but not limited to):
- History of immunodeficiency (congenital or acquired)
Show all 30Show fewer
- Neutropenia (absolute neutrophil count <1,500/mm3)
- History of solid-organ or bone marrow transplant
- History of current systemic autoimmune or autoinflammatory disease(s) requiring systemic immune-modulating drugs
- History of myeloproliferative disorder or active malignancy receiving cytotoxic chemotherapy
- Pre-existing severe pulmonary disease (i.e. steroid dependent asthma, COPD on home oxygen, or other restrictive/obstructive lung disease requiring home oxygen)
- Pre-existing severe left ventricular systolic dysfunction (i.e. LVEF <35%)
- Known or suspected active tuberculosis (TB), latent TB, or history of incompletely treated TB or at high risk for latent TB (from exposure or prior incarceration)
- History of active or latent viral hepatitis (i.e. Hepatitis B or C)
- Concomitant uncontrolled systemic bacterial or fungal infection
- Concomitant viral infection other than COVID-19 (e.g. Influenza, other respiratory viruses)
- History of chronic liver disease with portal hypertension
- History of end-stage renal disease on chronic renal replacement therapy
- Recent treatment with cell-depleting biological therapies (e.g., anti-CD20) within 12 months, cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-Interleukin [IL]-6 receptor [e.g. tocilizumab], or abatacept) within 8 weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within 12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks
- Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks
- Chronic or recent corticosteroid use > 10 mg/day
- Pregnant. Breast-feeding women are eligible with the decision to continue or discontinue breast-feeding during therapy taking into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother
- Enrolled in another investigational study using immunosuppressive therapy
- Known hypersensitivity to mavrilimumab or any of its excipients
- In the opinion of the investigator, unable to comply with the requirements to participate in the study
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug. Such methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
- Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
Read the detailed description
This prospective, Phase 2, multi-center, blinded randomized placebo-controlled study is designed to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe Covid-19 pneumonia and clinical and biological features of hyper-inflammation.
The study population includes patients who have severe pneumonia, defined as hospitalization due to Covid-19 with abnormal chest imaging and SpO2 <92% on room air or requirement for supplemental oxygen.
Enrollment: The study will be performed in approximately 4 months total, starting from the first patient enrolled with enrollment expected to complete within 2 months.
Follow-up period: The follow-up period is 60 days for each patient enrolled.
A total of 60 patients will be randomized using a 1:1 allocation ratio: 30 subjects will receive mavrilimumab, and 30 subjects will receive placebo infusion. The investigator, clinical team, and subject will be blinded to treatment assignment.
Participants will be identified by regular review of hospitalized COVID19 patients to evaluate for inclusion and exclusion criteria. Participants will then be approached in the standard manner by study investigator and coordinator/research nurse.
Research interventions will take place in the hospital in accordance with privacy standards.
The study team is informed on all study procedures and requirements with daily meetings and the opportunity to continuously update through secure channels.
In this multicenter consortium, each participating site will have their own IND for patients enrolled at their site. Data collection, data analysis, and randomization scheme will be performed by one site, Cleveland Clinic C5 Research.
- Being tested
- Mavrilimumab, Placebos
- Medical subject headings
- COVID-19, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MavrilimumabDrug
Also called KPL-301
Treatment infusion
PlacebosDrug
Placebo infusion
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Treatment infusion Receives: Drug: Mavrilimumab |
| Control | Placebo comparator | Placebo infusion Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Subjects Alive and Off of Oxygen at Day 14
Number of subjects alive and off of oxygen
Measured: 14 days
Secondary outcomes (1)
Number of Subjects Alive and Without Respiratory Failure at 28 Days
Number of subjects alive and without respiratory failure
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start2 Sep 2020
- Primary completion30 Nov 2020
- Study completion30 Nov 2020
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Kiniksa Pharmaceuticals, Ltd.
- Responsible party
- Sponsor
- Investigators
- Antonio Abbate, MD, PhD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463004
- Sponsor's protocol ID
- HM20019145
- Status last verified
- Aug 2021
- First submitted
- 7 Jul 2020
- Last updated
- 11 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cremer PC, Abbate A, Hudock K, McWilliams C, Mehta J, Chang SY, Sheng CC, Van Tassell B, Bonaventura A, Vecchie A, Carey B, Wang Q, Wolski KE, Rajendram P, Duggal A, Wang TS, Paolini JF, Trapnell BC; MASH-COVID study group. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jun;3(6):e410-e418. doi: 10.1016/S2665-9913(21)00070-9. Epub 2021 Mar 17.
PubMed 33754144
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation
- ClinicalTrials.gov ID
- NCT04463004
- Acronym / sponsor ID
- HM20019145
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Kiniksa Pharmaceuticals, Ltd.
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 30 Nov 2020 (actual)
- First posted
- 9 Jul 2020 (actual)
- Results
- Posted 11 Aug 2021
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 prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
Detailed description
This prospective, Phase 2, multi-center, blinded randomized placebo-controlled study is designed to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe Covid-19 pneumonia and clinical and biological features of hyper-inflammation.
The study population includes patients who have severe pneumonia, defined as hospitalization due to Covid-19 with abnormal chest imaging and SpO2 <92% on room air or requirement for supplemental oxygen.
Enrollment: The study will be performed in approximately 4 months total, starting from the first patient enrolled with enrollment expected to complete within 2 months.
Follow-up period: The follow-up period is 60 days for each patient enrolled.
A total of 60 patients will be randomized using a 1:1 allocation ratio: 30 subjects will receive mavrilimumab, and 30 subjects will receive placebo infusion. The investigator, clinical team, and subject will be blinded to treatment assignment.
Participants will be identified by regular review of hospitalized COVID19 patients to evaluate for inclusion and exclusion criteria. Participants will then be approached in the standard manner by study investigator and coordinator/research nurse.
Research interventions will take place in the hospital in accordance with privacy standards.
The study team is informed on all study procedures and requirements with daily meetings and the opportunity to continuously update through secure channels.
In this multicenter consortium, each participating site will have their own IND for patients enrolled at their site. Data collection, data analysis, and randomization scheme will be performed by one site, Cleveland Clinic C5 Research.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: MavrilimumabTreatment infusion |
| Control | Placebo comparator | Drug: PlacebosPlacebo infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent must be obtained before any assessment is performed
- Documented COVID19 pneumonia defined as positive SARS-CoV2 test AND abnormalities/ infiltrates on chest x-ray or computed tomography AND active fever or documented fever within 24-48 hours or ongoing anti-pyretic use to suppress fever
- Hypoxia (Room air SpO2 <92% or requirement for supplemental oxygen)
- Increased serum inflammatory marker (CRP > 5 mg/dL)
- Severity of disease warrants inpatient hospitalization
Key exclusion criteria (30 listed)
- Onset of COVID-19 symptoms >14 days
- Age < 18 years-old
- Hospitalized >7 days
- Mechanically ventilated
- Serious concomitant illness which in the opinion of the investigator precludes the patient from enrolling in the trial, including (but not limited to):
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 |
|---|---|---|
| MavrilimumabAlso: KPL-301Treatment infusion | Drug | Intervention |
| PlacebosPlacebo infusion | Drug | Control |
Primary outcome
Proportion of Subjects Alive and Off of Oxygen at Day 14
Time frame: 14 days
Number of subjects alive and off of oxygen
1 secondary outcome
Number of Subjects Alive and Without Respiratory Failure at 28 Days
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33754144Cremer PC, Abbate A, Hudock K, McWilliams C, Mehta J, Chang SY, Sheng CC, Van Tassell B, Bonaventura A, Vecchie A, Carey B, Wang Q, Wolski KE, Rajendram P, Duggal A, Wang TS, Paolini JF, Trapnell BC; MASH-COVID study group. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jun;3(6):e410-e418. doi: 10.1016/S2665-9913(21)00070-9. Epub 2021 Mar 17.
- 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.
Antonio Abbate, MD, PhD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mavrilimumab in people with COVID-19 and Sars-CoV2, run by Virginia Commonwealth University 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 5 inclusion and 30 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 11 Aug 2021. 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 phase mean?
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 11 Aug 2021). 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?
Proportion of Subjects Alive and Off of Oxygen at Day 14 (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04463004, which also lists 1 linked publication.
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 11 Aug 2021.