Ravulizumab and COVID-19
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| ClinicalTrials.gov Identifier: NCT04570397 |
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Recruitment Status :
Recruiting
First Posted : September 30, 2020
Last Update Posted : July 26, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Covid19 Thrombotic Microangiopathies Acute Kidney Injury | Drug: Ravulizumab | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 32 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | C5 Complement Inhbition Using Ravulizumab for the Treatment of COVID-19 Induced Thrombotic Microangiopathy |
| Actual Study Start Date : | December 18, 2020 |
| Estimated Primary Completion Date : | May 2023 |
| Estimated Study Completion Date : | November 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Interventional arm
ravulizumab
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Drug: Ravulizumab
Patients will receive weight-based dosing of ravulizumab on Days 1, 5, 10, and 15 along with the standard care. |
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No Intervention: Control arm
patients in this arm will recieve standard care
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- 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.
- Evaluation of pharmacokinetics of ravulizumab in participants with COVID-19 [ Time Frame: 120 days ]Evaluation of pharmacokinetics of ravulizumab in participants with COVID-19 Changes in ravulizumab concentration in plasma
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| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04570397
| Contact: Andrew M Siedlecki, M.D | 13148092879 | asiedlecki@partners.org | |
| Contact: Aliza Anwar Memon, M.B.B.S | 3479824073 | aamemon@bwh.harvard.edu |
| United States, Massachusetts | |
| Brigham and Women's Hospital | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Andrew M Siedlecki, M.D 314-809-2879 asiedlecki@partners.org | |
| Contact: Aliza Anwar Memon, M.B.B.S 3479824073 aamemon@bwh.harvard.edu | |
| Principal Investigator: Andrew M Siedlecki, M.D | |
| Sub-Investigator: Aliza Anwar Memon, M.B.B.S | |
| Responsible Party: | Andrew Michael Siedlecki, asistant professor, Brigham and Women's Hospital |
| ClinicalTrials.gov Identifier: | NCT04570397 |
| Other Study ID Numbers: |
092420 |
| First Posted: | September 30, 2020 Key Record Dates |
| Last Update Posted: | July 26, 2022 |
| Last Verified: | July 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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COVID-19 Acute Kidney Injury Thrombotic Microangiopathies Respiratory Tract Infections Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases |
Respiratory Tract Diseases Renal Insufficiency Kidney Diseases Urologic Diseases Thrombocytopenia Blood Platelet Disorders Hematologic Diseases Ravulizumab Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |