- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04418531
Convalescent Antibodies Infusion in COVID 19 Patients
A Pilot Study to Explore the Efficacy and Safety of Rescue Therapy With Antibodies From Convalescent Patients Obtained With Double-filtration Plasmapheresis (DFPP) and Infused in Patients With Coronavirus Disease 2019 (COVID-19) and Need of Oxygen Support Without Mechanical Ventilation
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has become a major concern all over the world.
Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease.
The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Moreover, plasma-exchange is expensive and requires large volumes of substitution fluid With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The use of plasma as a substitution fluid further increases treatment costs and is associated with risk of infections, allergic reactions and citrate-induced hypocalcemia. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion.
The aforementioned limitations of plasma therapy can be in part overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP)3. During DFPP, plasma is separated from cellular components by a plasma filter, and is then allowed to pass through a fractionator filter. Depending on the membrane cut-off, the fractionator filter retains larger molecules and returns fluid along with smaller molecules to the circulation. Thus, the selection of a membrane with an appropriate sieving coefficient for IgG allows to efficiently clear autoantibodies in patients with antibody-mediated diseases (e.g., macroglobulinemia, myasthenia gravis and rheumatoid arthritis) with negligible fluid losses and limited removal of albumin and coagulation factors1.
In patients with severe membranous nephropathy and high titer of autoreactive, nephritogenic antibodies against the podocyte-expressed M type phospholipase A2 receptor (PLA2R), DFPP accelerated anti PLA2R depletion4. Measurement of the antibody titer in treated patient and recovered fluid showed that antibody removal was extremely effective and that large part of antibodies was removed during the first DFPP procedure. This therapeutic regimen was safe and well tolerated and easy to apply4. In an ongoing pilot study we found that the same methodological approach can be used to remove circulating antibodies from patients who recovered from COVID 19 and to infuse these antibodies in patients with active viral infection. Treatment was well tolerated and preliminary findings are encouraging. Thus, in this novel pilot study we aim to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for patients with earlier stages of coronavirus (COVID-19) pneumonia requiring oxygen supply without mechanical ventilation.
Study Overview
Status
Conditions
Study Type
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Plasma Ig Donors
- Adult (>18 and <65-yr-old) men and women
- Convalescent donor who recovered from COVID 19 from at least 14 days according to the clinical and laboratory criteria defined by the Consiglio Superiore di Sanità on February 20, 2019 ("The recovered patient is the one who resolves the symptoms of COVID-19 infection and who is negative in two consecutive tests for the search for SARS-Cov-2, performed 24 hours apart") with the exceptions mentioned in the attached derogation (that is "no upper age limit to donation provided there are no clinical contraindications to the procedure and independent of documented evidence of two negative tests for SARS-Cov 2 naso-faringeal contamination")
- Male or female donor; if female only if nulliparous; in both cases with a negative history of blood component transfusions
- Careful clinical evaluation of the patient-donor with particular reference to the criteria established by current legislation to protect the health of the donor who donates by apheresis
- Presence of adequate levels of neutralizing anti-SARS-COV-2 antibodies;
- Biological qualification test negative defined by current indications (performed at SIMT of HPG23)
- Test negative for: HAV RNA, HEV RNA, PVB19 DNA (performed at HPG23)
- Informed written consent
Recipients
- >18 years of age
- COVID-19 pneumonia diagnosed by standard criteria (viral detection in naso-faringeal or bronco-alveolar lavage by RT-PCR for SARS-COV-2, typical Chest X Ray or CT Scan, ventilatory dysfunction not directly explained by heart failure or fluid overload)
- Respiratory failure (i.e. room air PaO2<60 mmHg) needing oxygen support with Venturi mask (FiO2 between 28 and 60%), non-rebreathing mask or high flow-nasal cannula (HFNC);
- Patient written informed consent
Exclusion Criteria:
- Need of Continuous Positive Airway Pressure (CPAP) ventilator support, Non-Invasive Ventilation (NIV) or intubation for invasive mechanical ventilation
- Involvement in any clinical trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Experimental antibodies (immunoglobulins) infusion
Anti-coronavirus obtained with double-filtration plasmapheresis (DFPP) from convalescent patients
|
Antibodies obtained from consenting convalescent donors will be administered to ten consecutive patients who fulfill the inclusion criteria .
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time to weaning of oxygen support
Time Frame: Through study completion, an average of 3 months
|
Through study completion, an average of 3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Chest XR or CT scan evaluation
Time Frame: Changes during the study up completion, an average of 3 months
|
Changes during the study up completion, an average of 3 months
|
|
Survival,
Time Frame: Through study completion, an average of 3 months
|
Through study completion, an average of 3 months
|
|
Viral titer
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
|
Anti COVID 19 IgG antibodies
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
|
Anti COVID 19 IgM antibodies
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
|
C5a concentration
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
C3a concentration
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum C5b-9 concentration Marker of complement activation
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum IL-6 levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum IL-1b levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum IFNγ levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum MCP-1 levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum TNFα levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum IL-10 levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum IL-2 levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Serum IL-7 levels
Time Frame: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Marker of complement activation in plasma.
|
Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- COVID-19
- Coronavirus Infections
- Pneumonia
- Pneumonia, Viral
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
- Immunoglobulins
- Immunoglobulins, Intravenous
Other Study ID Numbers
- DFPP COVID 19 Early
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pneumonia, Viral
-
Hospices Civils de LyonTerminatedCOVID-19 | Viral Pneumonia Human CoronavirusFrance
-
Cairo UniversityUnknown
-
University of Texas Southwestern Medical CenterWithdrawnBacterial Pneumonia | Viral PneumoniaUnited States
-
Zhong WangNot yet recruiting
-
Wecare Probiotics Co., Ltd.Not yet recruitingViral Pneumonia
-
Instituto Nacional de Ciencias Medicas y Nutricion...CompletedCoronavirus Infections | COVID-19 | Viral Pneumonia Human CoronavirusMexico
-
Francesco De CobelliCompleted
-
South Egypt Cancer InstituteRecruiting
-
University Hospital, LilleCompleted
-
University of TriesteCentro di Riferimento Oncologico - Aviano; National Institute for the Infectious...CompletedSevere Acute Respiratory Syndrome | Covid19 | Viral Pneumonia Human CoronavirusItaly
Clinical Trials on Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients
-
A.O. Ospedale Papa Giovanni XXIIIAferetica - Italy (BO)TerminatedCoronavirus Infection | Pneumonia, Ventilator-AssociatedItaly
-
Royal College of Surgeons in Ireland - Medical...Bahrain Defence Force Hospital; Salmaniya Medical Complex; Mohammed Bin Khalifa...Completed
-
Southwest Oncology GroupNational Cancer Institute (NCI); Roche-GenentechCompletedColorectal CancerUnited States
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedNeuroblastomaUnited States
-
OHSU Knight Cancer InstituteGenentech, Inc.; Oregon Health and Science UniversityWithdrawnAnatomic Stage III Breast Cancer AJCC v8 | Recurrent Ovarian Carcinoma | Anatomic Stage IV Breast Cancer AJCC v8 | Advanced Malignant Solid Neoplasm | Advanced Pancreatic Carcinoma | Stage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Recurrent... and other conditionsUnited States