COVID-19Phase 2NCT04381052
Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
A Phase 2 study testing Clazakizumab in people with COVID-19, run by Columbia University at 1 site in United States.
Trial summary
In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Clazakizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2020to 1 Apr 2021
- 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
- In order to be eligible to participate in this study, the patients must meet all of the following criteria:
- At least 18 years of age
- Confirmed COVID-19 disease (by Cobas SARS-CoV-2 real time reverse transcription polymerase chain reaction (RT-PCR) using nasopharyngeal swab sample, or equivalent test available to be performed by the Columbia University Irving Medical Center (CUIMC)/New York Presbyterian (NYP) clinical laboratory). Effort will be made to have the confirmatory test result <72 hours prior to enrollment however given overall clinical demand this may not be feasible in all cases.
- Respiratory failure manifesting as: Acute Respiratory Distress Syndrome (defined by a P/F ratio of <200), OR oxygen saturation (SpO2) < 90% on 4 liters (L) (actual or expected given higher O2 requirement) OR increasing O2 requirements over 24 hours, plus 2 or more of the following predictors for severe disease:
- CRP > 35 mg/L Ferritin > 500 ng/mL D-dimer > 1 mcg/L Neutrophil-Lymphocyte Ratio > 4 Lactate dehydrogenase (LDH) > 200 U/L Increase in troponin in patient w/out known cardiac disease
- Has a consent designee willing to provide informed consent on behalf of the patient (this assumes that a mechanically ventilated patients lacks capacity to consent on his/her own behalf. Should it be deemed that the patient has capacity to consent, consent may be obtained from the patient.)
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- Women of childbearing potential must be willing and able to use at least one highly effective contraceptive method for a period of 5 months following the study drug administration. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
- combined (estrogen and progestogen containing) hormonal contraception combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- vasectomized partner
- bilateral tubal occlusion
- true abstinence. when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence, such as calendar, ovulation, symptothermal, postovulation methods, and withdrawal are not acceptable methods of contraception.
- Men must be willing to use a double-barrier contraception from enrollment until at 5 months after the last dose of study drug, if not abstinent.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Evidence of irreversible injury deemed non-survivable even if the pulmonary failure recovers (for example severe anoxic brain injury)
- Known active inflammatory bowel disease
- Known active, untreated diverticulitis
- Known untreated bacteremia
- Pregnancy. (The protocol will exclude pregnant subjects given the lack of overall data on use of clazakizumab in pregnancy however the study team would consider a protocol revision should more than 3 potential pregnant study subjects be excluded on this basis).
- Known hypersensitivity to the clazakizumab
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center / New York Presbyerian Hospital
New York, New York, 10032
About this study
Official title: A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
Read the detailed description
The limited understanding of the clinical behavior of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the viral organism responsible for COVID-19 disease) is evolving on a daily basis. Reports from China indicate that a subset of patients with the worst clinical outcomes may manifest cytokine storm syndrome. Hypotheses that excess cytokines may trigger a secondary hemophagocytic lymphohistiocytosis (sHLH) have been proposed. Indeed, cytokine profiles consistent with this picture were observed in Chinese patients with severe pulmonary involvement. Specifically, elevated ferritin and interleukin-6 (IL-6) were associated with fatalities among the infected patients. A role for targeted anti-inflammatory and anti-cytokine therapies in the treatment of pulmonary hyperinflammation has been proposed.
Clazakizumab is a genetically engineered humanized immunoglobulin-1 (IgG1) monoclonal antibody (mAb) that binds with high affinity to human IL-6. This investigational agent is currently being studied as a treatment for chronic active antibody mediated rejection of renal allografts.
In this study investigators propose to administer clazakizumab to patients with life-threatening pulmonary failure secondary to COVID-19 disease.
- Conditions
- COVID-19
- Being tested
- Clazakizumab, Placebo
- Keywords
- Coronavirus, SARS-COVID-2
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClazakizumabDrug
Also called Clazakizumab solution
Dose is 25mg intravenously over 30 minutes.
PlaceboOther
Intravenously administered over 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Clazakizumab 25 mg | Experimental | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Clazakizumab 25 mg arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum C-reactive protein (CRP) will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25 mg clazakizumab will be given no later than day 3. Receives: Drug: Clazakizumab |
| Placebo | Placebo comparator | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo
Measured: 60 days
Secondary outcomes (12)
Cumulative Incidence of Intubation
Measured: 14 days
Time to Extubation
Measured: 14 days
Length of Intensive Care Unit (ICU) Stay
Measured: 14 days
Number of Patients Who Present a Decrease in C-reactive Protein (CRP)
Measured: 14 days
Number of Patients With Acute Kidney Injury (AKI)
Measured: 14 days
Number of Patients With a Need for Renal Replacement Therapy (RRT)
Measured: 14 days
Duration of Renal Replacement Therapy (RRT)
Measured: 60 days
Patient Survival
Number of participants alive at day 28.
Measured: 28 days
Patient Survival
Number of participants alive at day 60, end of study.
Measured: 60 days
Number of Patients With Hemodialysis
Measured: 60 days
Number of Patients With Continuous Renal Replacement Therapies (CRRT)
Measured: 60 days
Number of Patients With Peritoneal Dialysis
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start18 May 2020
- Primary completion1 Apr 2021
- Study completion1 Apr 2021
Why it stopped: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
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 COVID-19Studies of the same condition, open and under way.
- More trials run by Columbia 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
- Parallel groups
- Model description
- This is a randomized, double-blind, placebo-controlled, adaptive seamless Phase II/III design (ASD). The investigators propose the administration of an investigational drug in patients with high predicted short-term mortality secondary to COVID-19 disease. Patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- NYU Langone Health, CSL Behring
- Responsible party
- Sponsor
- Investigators
- David J. Cohen, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04381052
- Sponsor's protocol ID
- AAAT0142
- Status last verified
- Apr 2022
- First submitted
- 6 May 2020
- Last updated
- 8 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Coded data will be shared with New York University (NYU) Langone for the purpose of statistical analysis and scientific reporting.
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04381052
- Acronym / sponsor ID
- AAAT0142
- Conditions
- COVID-19
- Keywords
- Coronavirus, SARS-COVID-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- NYU Langone Health, CSL Behring
- Study start
- 18 May 2020 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 8 May 2020 (actual)
- Results
- Posted 8 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
Detailed description
The limited understanding of the clinical behavior of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the viral organism responsible for COVID-19 disease) is evolving on a daily basis. Reports from China indicate that a subset of patients with the worst clinical outcomes may manifest cytokine storm syndrome. Hypotheses that excess cytokines may trigger a secondary hemophagocytic lymphohistiocytosis (sHLH) have been proposed. Indeed, cytokine profiles consistent with this picture were observed in Chinese patients with severe pulmonary involvement. Specifically, elevated ferritin and interleukin-6 (IL-6) were associated with fatalities among the infected patients. A role for targeted anti-inflammatory and anti-cytokine therapies in the treatment of pulmonary hyperinflammation has been proposed.
Clazakizumab is a genetically engineered humanized immunoglobulin-1 (IgG1) monoclonal antibody (mAb) that binds with high affinity to human IL-6. This investigational agent is currently being studied as a treatment for chronic active antibody mediated rejection of renal allografts.
In this study investigators propose to administer clazakizumab to patients with life-threatening pulmonary failure secondary to COVID-19 disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This is a randomized, double-blind, placebo-controlled, adaptive seamless Phase II/III design (ASD). The investigators propose the administration of an investigational drug in patients with high predicted short-term mortality secondary to COVID-19 disease. Patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.
| Arm | Type | Receives |
|---|---|---|
| Clazakizumab 25 mg | Experimental | Drug: ClazakizumabThe first dose will be administered as soon as possible after the patient is enrolled and randomized into the Clazakizumab 25 mg arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum C-reactive protein (CRP) will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25 mg clazakizumab will be given no later than day 3. |
| Placebo | Placebo comparator | Other: PlaceboThe first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- In order to be eligible to participate in this study, the patients must meet all of the following criteria:
- At least 18 years of age
- Confirmed COVID-19 disease (by Cobas SARS-CoV-2 real time reverse transcription polymerase chain reaction (RT-PCR) using nasopharyngeal swab sample, or equivalent test available to be performed by the Columbia University Irving Medical Center (CUIMC)/New York Presbyterian (NYP) clinical laboratory). Effort will be made to have the confirmatory test result <72 hours prior to enrollment however given overall clinical demand this may not be feasible in all cases.
- Respiratory failure manifesting as: Acute Respiratory Distress Syndrome (defined by a P/F ratio of <200), OR oxygen saturation (SpO2) < 90% on 4 liters (L) (actual or expected given higher O2 requirement) OR increasing O2 requirements over 24 hours, plus 2 or more of the following predictors for severe disease:
- CRP > 35 mg/L Ferritin > 500 ng/mL D-dimer > 1 mcg/L Neutrophil-Lymphocyte Ratio > 4 Lactate dehydrogenase (LDH) > 200 U/L Increase in troponin in patient w/out known cardiac disease
Key exclusion criteria (7 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Evidence of irreversible injury deemed non-survivable even if the pulmonary failure recovers (for example severe anoxic brain injury)
- Known active inflammatory bowel disease
- Known active, untreated diverticulitis
- Known untreated bacteremia
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 |
|---|---|---|
| ClazakizumabAlso: Clazakizumab solutionDose is 25mg intravenously over 30 minutes. | Drug | Clazakizumab 25 mg |
| PlaceboIntravenously administered over 30 minutes. | Other | Placebo |
Primary outcome
Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo
Time frame: 60 days
12 secondary outcomes
Cumulative Incidence of Intubation
Time frame: 14 days
Time to Extubation
Time frame: 14 days
Length of Intensive Care Unit (ICU) Stay
Time frame: 14 days
Number of Patients Who Present a Decrease in C-reactive Protein (CRP)
Time frame: 14 days
Number of Patients With Acute Kidney Injury (AKI)
Time frame: 14 days
Number of Patients With a Need for Renal Replacement Therapy (RRT)
Time frame: 14 days
Duration of Renal Replacement Therapy (RRT)
Time frame: 60 days
Patient Survival
Time frame: 28 days
Patient Survival
Time frame: 60 days
Number of Patients With Hemodialysis
Time frame: 60 days
Number of Patients With Continuous Renal Replacement Therapies (CRRT)
Time frame: 60 days
Number of Patients With Peritoneal Dialysis
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Coded data will be shared with New York University (NYU) Langone for the purpose of statistical analysis and scientific reporting.
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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.
David J. Cohen, MD principal investigator
Columbia 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 Clazakizumab in people with COVID-19, run by Columbia 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 15 inclusion and 7 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: stopped early, as of the sponsor's last update on 8 Apr 2022. 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 8 Apr 2022). 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?
Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo (time frame: 60 days). 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 8 Apr 2022; AzTrials last refreshed its copy on 8 Nov 2026.