Covid19Phase 3NCT04570397
Ravulizumab and COVID-19
A Phase 3 study testing Ravulizumab in people with Covid19 and Thrombotic Microangiopathies, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Ultomiris (Ravulizumab), is a monoclonal antibody that specifically targets terminal complement products and is proposed for the treatment of COVID-19 induced microvasculature injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute kidney injury (AKI). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Covid19, Thrombotic Microangiopathies, Acute Kidney Injury
- What is being tested?
- Ravulizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2020to Nov 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or Females 18 years of age or above and weighing 40kg or above at the time of providing informed consent.
- A clinical diagnosis of thrombotic microangiopathy will then be applied to include the following criteria: i) D-dimer > 100% the upper limit of the reference range and ii) serum creatinine >25% of the normal range or iii) >25% increase from patient's baseline serum creatinine.
- Diagnosis of SARS-CoV-2 infection within 90 days prior to enrollment
Who cannot join
- Participant is not expected to survive more than 24 hours.
- Participant has an unresolved Neisseria Meningitides infection.
- Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: C5 Complement Inhbition Using Ravulizumab for the Treatment of COVID-19 Induced Thrombotic Microangiopathy
Ultomiris (Ravulizumab), is a monoclonal antibody that specifically targets terminal complement products and is proposed for the treatment of COVID-19 induced microvasculature injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute kidney injury (AKI). Ravulizumab is to be used for participants with a confirmed diagnosis of COVID-19 who clinically or diagnostically present with deteriorating renal function. Ravulizumab causes immediate and sustained inhibition of the terminal complement cascade. The use of ravulizumab could ameliorate COVID-19 induced kidney injury due to TMA, shorten hospital stay, and improve the overall survival.
Read the detailed description
The novel coronavirus (COVID 19) is responsible for the current pandemic with the numbers of diagnoses and fatalities rising daily. It is reported that of those requiring medical intensive care almost 49% will expire prior hospital discharge. The initial peak of hospitalized patients in Boston, MA occurred on April 15, 2020 however new presentations continue to manifest at a local and national level.
The exact pathophysiology is still not clear. There are various theories that explain the pathophysiology which includes but is not limited to direct viral damage via the angiotensin-converting enzyme 2 receptor, systemic inflammatory response with cytokine storm, and aggravated hypoxia.
Recently, it has been observed that signs and symptoms of severe COVID 19 describe complement-mediated TMA rather than the sepsis induced coagulopathy. This strengthens the hypothesis that complement inhibition by C5a inhibitor, Ultomiris (ravulizumab) could ameliorate COVID 19 induced TMA, improve renal function, shorten the hospital stay and reduce the overall mortality.
In those affected with severe or fatal COVID-19, there is evidence of end-organ damage with acute kidney injury which has heightened the interest in studying the excessive cytokine release and its overall effect in the form of multi-organ failure.
Ultomiris (Ravulizumab) is a long acting second generation monoclonal antibody against a terminal complement product C5a and is FDA approved for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and atypical hemolytic uremic syndrome.The benefit of Ultomiris has not been clinically evaluated in COVID 19 induced TMA.
Recently, ravulizumab has been utilized in the setting of a phase 3 clinical trial for the treatment of COVID 19 induced pneumonia, acute lung injury and acute respiratory distress. As it binds to C5 and impedes the cleavage of C5 by C5 convertase to generate C5a and membrane attack complex, ravulizumab could possibly improve the renal function in COVID 19 induced TMA and potentially improve overall survival, due to similar pathophysiology in the microvasculature of the kidney. More so, studies are being conducted to determine renal and cardiovascular sequelae of COVID-19 infection, which further enhances the interest to closely examine and evaluate those patients presenting 30-60 days after COVID-19 infection with signs of renal failure. There remains an unmet clinical need to investigate this approach with a randomized controlled trial to determine if complement cascade inhibition can improve the clinical outcome for COVID 19 induced acute kidney injury as measured by improvement of renal function and decline in the overall morbidity and mortality.
- Conditions
- Covid19, Thrombotic Microangiopathies, Acute Kidney Injury
- Being tested
- Ravulizumab
- Medical subject headings
- COVID-19, Thrombotic Microangiopathies, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RavulizumabDrug
Patients will receive weight-based dosing of ravulizumab on Days 1, 5, 10, and 15 along with the standard care.
| Study group | Role | What they receive |
|---|---|---|
| Interventional arm | Experimental | ravulizumab Receives: Drug: Ravulizumab |
| Control arm | No intervention | patients in this arm will recieve standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the efficacy of ravulizumab to ameliorate SARS-CoV-2 (COVID-19)-induced acute kidney injury manifesting as thrombotic microangiopathy.
50% improvement in estimated glomerular filtration rate compared to conventional therapy within 30 days of treatment for COVID-19-induced acute kidney injury.
Measured: 30 days
Secondary outcomes (1)
Evaluation of pharmacokinetics of ravulizumab in participants with COVID-19
Evaluation of pharmacokinetics of ravulizumab in participants with COVID-19 Changes in ravulizumab concentration in plasma
Measured: 120 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2020
- Study start18 Dec 2020
- Primary completionMay 2023 (estimated)
- Study completionNov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Michael Siedlecki, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04570397
- Sponsor's protocol ID
- 092420
- Status last verified
- Dec 2022
- First submitted
- 29 Sep 2020
- Last updated
- 4 Jan 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- C5 Complement Inhbition Using Ravulizumab for the Treatment of COVID-19 Induced Thrombotic Microangiopathy
- ClinicalTrials.gov ID
- NCT04570397
- Acronym / sponsor ID
- 092420
- Conditions
- Covid19, Thrombotic Microangiopathies, Acute Kidney Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 18 Dec 2020 (actual)
- Primary completion
- May 2023 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 30 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ultomiris (Ravulizumab), is a monoclonal antibody that specifically targets terminal complement products and is proposed for the treatment of COVID-19 induced microvasculature injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute kidney injury (AKI). Ravulizumab is to be used for participants with a confirmed diagnosis of COVID-19 who clinically or diagnostically present with deteriorating renal function. Ravulizumab causes immediate and sustained inhibition of the terminal complement cascade. The use of ravulizumab could ameliorate COVID-19 induced kidney injury due to TMA, shorten hospital stay, and improve the overall survival.
Detailed description
The novel coronavirus (COVID 19) is responsible for the current pandemic with the numbers of diagnoses and fatalities rising daily. It is reported that of those requiring medical intensive care almost 49% will expire prior hospital discharge. The initial peak of hospitalized patients in Boston, MA occurred on April 15, 2020 however new presentations continue to manifest at a local and national level.
The exact pathophysiology is still not clear. There are various theories that explain the pathophysiology which includes but is not limited to direct viral damage via the angiotensin-converting enzyme 2 receptor, systemic inflammatory response with cytokine storm, and aggravated hypoxia.
Recently, it has been observed that signs and symptoms of severe COVID 19 describe complement-mediated TMA rather than the sepsis induced coagulopathy. This strengthens the hypothesis that complement inhibition by C5a inhibitor, Ultomiris (ravulizumab) could ameliorate COVID 19 induced TMA, improve renal function, shorten the hospital stay and reduce the overall mortality.
In those affected with severe or fatal COVID-19, there is evidence of end-organ damage with acute kidney injury which has heightened the interest in studying the excessive cytokine release and its overall effect in the form of multi-organ failure.
Ultomiris (Ravulizumab) is a long acting second generation monoclonal antibody against a terminal complement product C5a and is FDA approved for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and atypical hemolytic uremic syndrome.The benefit of Ultomiris has not been clinically evaluated in COVID 19 induced TMA.
Recently, ravulizumab has been utilized in the setting of a phase 3 clinical trial for the treatment of COVID 19 induced pneumonia, acute lung injury and acute respiratory distress. As it binds to C5 and impedes the cleavage of C5 by C5 convertase to generate C5a and membrane attack complex, ravulizumab could possibly improve the renal function in COVID 19 induced TMA and potentially improve overall survival, due to similar pathophysiology in the microvasculature of the kidney. More so, studies are being conducted to determine renal and cardiovascular sequelae of COVID-19 infection, which further enhances the interest to closely examine and evaluate those patients presenting 30-60 days after COVID-19 infection with signs of renal failure. There remains an unmet clinical need to investigate this approach with a randomized controlled trial to determine if complement cascade inhibition can improve the clinical outcome for COVID 19 induced acute kidney injury as measured by improvement of renal function and decline in the overall morbidity and mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interventional arm | Experimental | Drug: Ravulizumabravulizumab |
| Control arm | No intervention | –patients in this arm will recieve standard care |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males or Females 18 years of age or above and weighing 40kg or above at the time of providing informed consent.
- A clinical diagnosis of thrombotic microangiopathy will then be applied to include the following criteria: i) D-dimer > 100% the upper limit of the reference range and ii) serum creatinine >25% of the normal range or iii) >25% increase from patient's baseline serum creatinine.
- Diagnosis of SARS-CoV-2 infection within 90 days prior to enrollment
Key exclusion criteria (3 listed)
- Participant is not expected to survive more than 24 hours.
- Participant has an unresolved Neisseria Meningitides infection.
- Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
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 |
|---|---|---|
| RavulizumabPatients will receive weight-based dosing of ravulizumab on Days 1, 5, 10, and 15 along with the standard care. | Drug | Interventional arm |
Primary outcome
Assess the efficacy of ravulizumab to ameliorate SARS-CoV-2 (COVID-19)-induced acute kidney injury manifesting as thrombotic microangiopathy.
Time frame: 30 days
50% improvement in estimated glomerular filtration rate compared to conventional therapy within 30 days of treatment for COVID-19-induced acute kidney injury.
1 secondary outcome
Evaluation of pharmacokinetics of ravulizumab in participants with COVID-19
Time frame: 120 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ravulizumab in people with Covid19 and Thrombotic Microangiopathies, run by Brigham and Women's Hospital 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 3 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 4 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Assess the efficacy of ravulizumab to ameliorate SARS-CoV-2 (COVID-19)-induced acute kidney injury manifesting as thrombotic microangiopathy. (time frame: 30 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 4 Jan 2023.