Brief Summary
The purpose of this study is to find out if Berinert can improve kidney function in the first year after transplant and to find out what effects, good or bad, Berinert will have in the kidney recipient. This research study will compare Berinert to placebo. The placebo looks exactly like Berinert but does not contain any active drug. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons. Neither you or the study doctor can choose or know which group is assigned.
The primary objective is to test whether intrarenal artery C1 esterase inhibitor (C1INH) injection into the donor kidney prior to transplantation improves kidney function in recipients of high risk, deceased donor kidney transplants as measured by 12-month Estimated Glomerular Filtration Rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI)
The primary objective is to test whether intrarenal artery C1 esterase inhibitor (C1INH) injection into the donor kidney prior to transplantation improves kidney function in recipients of high risk, deceased donor kidney transplants as measured by 12-month Estimated Glomerular Filtration Rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI)
Brief Title
Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (IMPROVE TRIAL)
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Kidney Transplant
Eligibility Criteria
Inclusion Criteria:
1. Participant must be able to understand and provide informed consent
2. Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
3. Recipients who are ABO compatible with donor allograft
4. Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
5. Female participants of childbearing potential must have a negative pregnancy test upon study entry
6. All participants with reproductive potential must agree to use highly effective contraception for at least 12-moths post-transplant. Oral estrogen containing contraception must not be used during the first 3 months post-transplant
7. Hepatitis C Virus Ab positive participants with negative Hepatitis C virus (HCV) Polymerase chain reaction (PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
8. Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they will be treated with the intent of inducing a sustained virologic remission
9. Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
10. Vaccines up to date per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials
11. Anticipated Cold Ischemia Time (CIT) \>=12 hours
12. Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours
13. Patients with normal coagulation
Exclusion Criteria:
1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
2. Any prior or concurrent non-renal solid organ, or cellular transplant, or waitlisted for multi-organ transplant
3. Patients receiving enbloc kidneys
4. Kidneys receiving normothermic perfusion
5. Patients with a known pro-thrombotic disorder
6. Patients with a history of thrombosis or hyper-coagulable state, excluding dialysis access clotting
7. Body mass index (BMI) \>=40 kg/m\^2
8. Patients with a history of Hereditary Angioedema or use of C1 esterase inhibitor (C1INH) containing products or recombinant C1INH within 15 days prior to study entry
9. Patients with a known hypersensitivity to treatment with Berinert
10. Patients requiring chronic anti-coagulation or anti-platelet therapy. ASA and NSAIDS are allowed
11. Presence of active malignancy or history of malignancy less than 5 years in remission, excluding adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin
12. Patients who are positive for Hep B infection (Hepatitis B surface antigen (HBsAg)+ or anti-HBcore +)
13. Any active infection
14. Human immunodeficiency virus (HIV) infection
15. Enrollment in another investigational trial
16. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
17. Current or planned use of immunomodulatory agents including but not limited to rituximab, belatacept, eculizumab, JAK inhibitors, anti-TNF agents
18. Female participants who are pregnant or lactating
19. Past or current medical problems, inclusive of mental health and substance abuse concerns, or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
1. Participant must be able to understand and provide informed consent
2. Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
3. Recipients who are ABO compatible with donor allograft
4. Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
5. Female participants of childbearing potential must have a negative pregnancy test upon study entry
6. All participants with reproductive potential must agree to use highly effective contraception for at least 12-moths post-transplant. Oral estrogen containing contraception must not be used during the first 3 months post-transplant
7. Hepatitis C Virus Ab positive participants with negative Hepatitis C virus (HCV) Polymerase chain reaction (PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
8. Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they will be treated with the intent of inducing a sustained virologic remission
9. Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
10. Vaccines up to date per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials
11. Anticipated Cold Ischemia Time (CIT) \>=12 hours
12. Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours
13. Patients with normal coagulation
Exclusion Criteria:
1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
2. Any prior or concurrent non-renal solid organ, or cellular transplant, or waitlisted for multi-organ transplant
3. Patients receiving enbloc kidneys
4. Kidneys receiving normothermic perfusion
5. Patients with a known pro-thrombotic disorder
6. Patients with a history of thrombosis or hyper-coagulable state, excluding dialysis access clotting
7. Body mass index (BMI) \>=40 kg/m\^2
8. Patients with a history of Hereditary Angioedema or use of C1 esterase inhibitor (C1INH) containing products or recombinant C1INH within 15 days prior to study entry
9. Patients with a known hypersensitivity to treatment with Berinert
10. Patients requiring chronic anti-coagulation or anti-platelet therapy. ASA and NSAIDS are allowed
11. Presence of active malignancy or history of malignancy less than 5 years in remission, excluding adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin
12. Patients who are positive for Hep B infection (Hepatitis B surface antigen (HBsAg)+ or anti-HBcore +)
13. Any active infection
14. Human immunodeficiency virus (HIV) infection
15. Enrollment in another investigational trial
16. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
17. Current or planned use of immunomodulatory agents including but not limited to rituximab, belatacept, eculizumab, JAK inhibitors, anti-TNF agents
18. Female participants who are pregnant or lactating
19. Past or current medical problems, inclusive of mental health and substance abuse concerns, or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
Inclusion Criteria
Inclusion Criteria:
1. Participant must be able to understand and provide informed consent
2. Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
3. Recipients who are ABO compatible with donor allograft
4. Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
5. Female participants of childbearing potential must have a negative pregnancy test upon study entry
6. All participants with reproductive potential must agree to use highly effective contraception for at least 12-moths post-transplant. Oral estrogen containing contraception must not be used during the first 3 months post-transplant
7. Hepatitis C Virus Ab positive participants with negative Hepatitis C virus (HCV) Polymerase chain reaction (PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
8. Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they will be treated with the intent of inducing a sustained virologic remission
9. Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
10. Vaccines up to date per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials
11. Anticipated Cold Ischemia Time (CIT) \>=12 hours
12. Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours
13. Patients with normal coagulation
1. Participant must be able to understand and provide informed consent
2. Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
3. Recipients who are ABO compatible with donor allograft
4. Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
5. Female participants of childbearing potential must have a negative pregnancy test upon study entry
6. All participants with reproductive potential must agree to use highly effective contraception for at least 12-moths post-transplant. Oral estrogen containing contraception must not be used during the first 3 months post-transplant
7. Hepatitis C Virus Ab positive participants with negative Hepatitis C virus (HCV) Polymerase chain reaction (PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
8. Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they will be treated with the intent of inducing a sustained virologic remission
9. Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
10. Vaccines up to date per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials
11. Anticipated Cold Ischemia Time (CIT) \>=12 hours
12. Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours
13. Patients with normal coagulation
Gender
All
Gender Based
false
Keywords
Kidney transplant
Deceased donor
Intragraft injection
C1 esterase inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT06919003
Org Class
Nih
Org Full Name
National Institute of Allergy and Infectious Diseases (NIAID)
Org Study Id
DAIT RTB-021
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (RTB-021)
Primary Outcomes
Outcome Description
Measured as Estimated Glomerular Filtration Rate Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) in ml/min/1.73m\^2
Outcome Measure
Difference between study arms in renal function
Outcome Time Frame
At 12-months post-transplantation
Secondary Outcomes
Outcome Description
The iBox scoring system is a composite biomarker panel. The full iBox scoring system consists of 4 elements all obtained 1-year post-transplant: a) eGFR (MDRD), b) DSA, c) urinary protein/creatine ratio, and d) histological abnormalities on a surveillance biopsy.
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Comparison between the treated and control group of the full iBox score
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of biopsy proven acute rejection (BPAR)
Outcome Description
Measured as spot urine protein/creatinine \>1 g/g
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of proteinuria
Outcome Description
Defined as the incidence of de novo DSA on standard of care or protocol directed blood draws up to and including the 12-month protocol blood draw.
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA)
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of Grade 3 or higher infections
Outcome Time Frame
Within 4 weeks after transplantation
Outcome Measure
Incidence of Grade 3 or higher intraoperative or postoperative hemorrhage
Outcome Description
Excluding superficial thrombophlebitis, catheter-related thrombosis and dialysis access thrombosis
Outcome Time Frame
Within 4 weeks after transplantation
Outcome Measure
Incidence of thrombotic or thromboembolic events
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of T cell mediated rejection (TCMR) that is steroid resistant
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of TCMR that is BANFF grade 2 or higher
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of antibody mediated rejection (ABMR)
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of death
Outcome Time Frame
At 12-months post-transplantation
Outcome Measure
Incidence of Graft loss (including primary non function)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Enver Akalin
Investigator Email
eakalin@montefiore.org
Investigator Phone
718-920-4815
Investigator Department
Medicine
Investigator Division
Nephrology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Nephrology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- VASCULAR DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Lung --- HYPERSENSITIVITY, IMMEDIATE
Lung --- HYPERSENSITIVITY
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
Infectious Disease --- IMMUNOLOGIC DEFICIENCY SYNDROMES
MeSH Terms
ANGIOEDEMAS, HEREDITARY
ANGIOEDEMA
VASCULAR DISEASES
CARDIOVASCULAR DISEASES
HEREDITARY COMPLEMENT DEFICIENCY DISEASES
PRIMARY IMMUNODEFICIENCY DISEASES
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
URTICARIA
SKIN DISEASES, VASCULAR
SKIN DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
HYPERSENSITIVITY, IMMEDIATE
HYPERSENSITIVITY
IMMUNE SYSTEM DISEASES
IMMUNOLOGIC DEFICIENCY SYNDROMES
COMPLEMENT C1 INHIBITOR PROTEIN
GLYCOPROTEINS
GLYCOCONJUGATES
CARBOHYDRATES
COMPLEMENT C1 INACTIVATOR PROTEINS
SERPINS
PEPTIDES
AMINO ACIDS, PEPTIDES, AND PROTEINS
COMPLEMENT INACTIVATOR PROTEINS
COMPLEMENT SYSTEM PROTEINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS