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There is one clinical trial.
A randomized controlled study to assess the safety and efficacy and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation.
Description: Free from IS is defined as not taking any immunosuppression medications and not having to take immunosuppression medications since their withdrawal. Biopsy proven acute rejection Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
Measure: Proportion of FCR001 recipients who are free from immunosuppression (IS), without biopsy proven acute rejection (BPAR) at 24 months post-transplant Time: 24 months post-transplantDescription: Renal function is evaluated by estimated glomerular filtration rate (eGFR) calculated using the MDRD4 formula (Coresh et al. 2003). Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where C is the serum concentration of creatinine [mg/dL], A is patient age at sample collection date [years], G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1.
Measure: Change in renal function by Modification of Diet in Renal Disease (MDRD4) from post-transplant baseline (Month 1) to Month 24 in FCR001 recipients Time: 24 months post-transplantDescription: Free from IS is defined as not taking any immunosuppression medications and not having to take immunosuppression medications since their withdrawal. Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
Measure: Proportion of FCR001 recipients free from IS, without BPAR, at Month 36 and 60 Time: Month 36 and 60 post transplantDescription: Renal function is evaluated by estimated glomerular filtration rate (eGFR) calculated with the MDRD4 formula (Coresh et al. 2003). This formula is based on the four (4) variables of age, gender, ethnicity and serum creatinine.
Measure: Allograft function (eGFR by MDRD4) and change in eGFR from Month 1 to Month 24, 36, and Month 60, by treatment Time: Month 1 (post-transplant) to Month 24, 36, and Month 60Description: Estimated glomerular filtration rate (eGFR) is calculated with the MDRD4 formula (Coresh et al. 2003).
Measure: Slope and difference in slope of estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD4) over time to Month 24, 36, and 60, by treatment Time: Month 24, 36, and 60Description: Estimated glomerular filtration rate (eGFR) is calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (Levey et al. 2009).
Measure: Allograft function (eGFR) and change in renal allograft function from Month 1 to Months 24, 36 and 60 by treatment group, using the CKD-EPI formula Time: Month 1 (post transplant) to Month 24, 36, and Month 60Description: Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018). Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation. Loss to follow-up is a subject whose status is unclear because he/she fails to appear for study visits without stating an intention to withdraw and did not respond to repeated attempts of contact, who did not experience graft loss or death from Day 1 and whose last day of contact was prior to study Month 60.
Measure: Time to the event for the composite of BPAR, graft loss, death or lost to follow-up and for each component, by treatment group Time: Month 1 (post transplant) to Month 6, 12, 24, 36, and 60Description: Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018). Graft loss is defined by 56 consecutive days of hemodialysis or re-transplantation.
Measure: Incidence of composite endpoint of BPAR, graft loss or death, by treatment group Time: Months 12, 24, 36 and 60Description: Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018). Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation. Loss to follow-up is a subject whose status is unclear because he/she fails to appear for study visits without stating an intention to withdraw and did not respond to repeated attempts of contact, who did not experience graft loss or death from Day 1 and whose last day of contact was prior to study Month 60.
Measure: Incidence of composite endpoint of BPAR, graft loss, or death and lost to follow-up, by treatment group Time: Months 12, 24, 36 and 60Description: Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018). Treated BPAR are those BPARs treated with antirejection medications. BPAR and treated BPAR will be characterized by severity, type and steroid resistance.
Measure: Incidence of BPAR and treated BPAR by severity and type (Banff 2017) and steroid-resistance, by treatment group Time: Months 12, 24, 36 and 60Description: Acute rejection includes both clinically suspected and BPAR Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
Measure: Incidence of acute rejection Time: Months 12, 24, 36 and 60Description: Newly formed anti-human leukocyte donor-specific antibodies
Measure: Incidence of de novo donor-specific antibodies Time: Months 12, 24, 36 and 60Description: Kidney biopsies will be assessed for new or worsening abnormal histologic findings of cellular or antibody-mediated chronic rejection, chronic glomerulopathy, renal tubular atrophy and interstitial fibrosis, C4d (degradation product of activated complement factor C4 and is a sensitive marker for antibody-dependent humoral rejection) in peritubular capillaries, calcineurin inhibitor induced damage, recurrence of the primary condition leading to renal transplant, and BK viral nephropathy.
Measure: Incidence or worsening of abnormal histologic findings of cellular or antibody-mediated chronic rejection, chronic glomerulopathy, tubular atrophy and interstitial fibrosis, C4d, calcineurin inhibitor induced damage, disease recurrence, BK Time: Months 12, 24, 36 and 60Description: Renal replacement therapy is defined by the need for hemodialysis following kidney transplant which is not due to delayed graft function.
Measure: Incidence of renal replacement therapy by treatment group Time: Months 12, 24, 36 and 60Description: BPAR Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018). Estimated glomerular filtration rate (eGFR) is calculated using the MDRD4 formula (Coresh et al. 2003).
Measure: Incidence of BPAR or eGFR <50 mL/min by treatment group Time: Months 12, 24, 36 and 60Description: Estimated glomerular filtration rate (eGFR), calculated by the MDRD4 formula (Coresh et al. 2003), is used to determine the stage of chronic kidney disease (CKD). The 5 stages of CKD based on GFR are: Stage 1 is GFR ≥ 90 mL/min/1.73 m^2; Stage 2 is GFR from 60 to 89 mL/min/1.73 m^2; Stage 3 is GFR from 30 to 59 mL/min/1.73 m^2; Stage 4 is GFR from 15 to 29 mL/min/1.73 m^2 and Stage 5 is GFR <15 mL/min/1.73 m^2.
Measure: Categorical distribution of eGFR according to CKD staging classification by treatment Time: Months 12, 24, 36 and 60Description: An Adverse Event (AE) is any untoward medical occurrence (ie, any unfavorable and unintended sign, symptom or disease). A Serious Adverse Event is defined as any AE (appearance of or worsening of any pre-existing undesirable sign, symptom or medical conditions) which meets any one of the following criteria: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, or is medically significant
Measure: Incidence and severity of adverse events (AEs; including infections), serious adverse events (SAEs) Time: Months 12, 24, 36 and 60Description: BK virus infection is defined by virus detected by PCR-based assay in blood (viremia) or urine (viruria). BK infection of the kidney is defined as histologic evidence of BK viral infection on kidney biopsy and positive BK virus detected in blood or urine.
Measure: Incidence of BK viremia, viruria, infection, and nephropathy by treatment Time: Months 12, 24, 36 and 60Description: Adverse event reporting of proteinuria, neurotoxicity, anemia, diabetes, hypertension, and dyslipidemia.
Measure: Incidence of the adverse events of proteinuria, neurotoxicity, anemia, diabetes, hypertension, and dyslipidemia and their composite, by treatment Time: Months 12, 24, 36 and 60Description: Proteinuria, a marker of renal dysfunction, is assessed by a urinary protein/creatinine ratio using urine sample protein and creatinine concentration measures. The ratio is a surrogate for a 24-hour urinary protein measurement. Similarly, a urinary albumin/creatinine ratio is a sensitive assessment of low levels of urine proteinuria.
Measure: Urinary protein and albumin excretion, estimated by urinary protein/creatinine and urinary albumin/creatinine ratios by treatment group Time: Months 12, 24, 36 and 60Description: Adverse events of major cardiovascular events and malignancies.
Measure: Incidence of major cardiovascular events and malignancies by treatment group Time: Months 12, 24, 36 and 60Description: The 36-Item Short Form Health Survey is a patient-reported outcome measure which assesses overall physical function, general health and social/psychological factors. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measure: Subject quality of life according to 36-Item Short Form Health Survey (SF-36) will be analyzed descriptively by treatment group Time: Months 12, 24, 36 and 60Description: The End-Stage Renal Disease Symptom Checklist (ESRD-SCL) is also an outcome measure developed specifically for and validated in the end stage renal disease population. The ESRD-SCL covers six dimensions with a total of 43 items: limited physical capacity (10 items), limited cognitive capacity (8 items), cardiac and renal dysfunction (7 items), side effects of corticosteroids (5 items), increased hair and gum growth (5 items) as well as transplantation-associated psychological distress (8 items). All questions are scored on a five-point Likert scale. The higher the score the more unfavorable symptoms were reported.
Measure: Subject quality of life according to End-Stage Renal Disease Symptom Checklist (ESRD-SCL) will be analyzed descriptively by treatment group Time: Months 12, 24, 36 and 60Description: Hospital admissions and readmission by ward/unit and duration will be collected through serious adverse event reporting.
Measure: Incidence and duration of hospitalization and readmission, according to type of ward/unit Time: Months 12, 24, 36 and 60Description: Graft loss and death are used to determine graft survival and patient survival respectively. Both will be evaluated in FCR001 recipients who achieve a donor chimerism of >50% donor T-cells measured in recipient blood but then falls below 50% T-cells. Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.
Measure: Graft and patient survival and eGFR in FCR001 recipients who are only transiently chimeric Time: Month 24, 36, and 60Description: An Adverse Event is any untoward medical occurrence (ie, any unfavorable and unintended sign, symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. A Serious Adverse Event is defined as any AE (appearance of or worsening of any pre-existing undesirable sign, symptom or medical conditions) which meets any one of the following criteria: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, or is medically significant. Adverse events and Serious Adverse Events for FCR001 donors will be summarized.
Measure: To describe the incidence and severity of AEs (including infections) and SAEs among FCR001 donors Time: Month 24, 36, and 60Description: In this composite endpoint, acute rejection is defined as a BPAR Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018). Renal graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation. Loss to follow-up is a subject whose status is unclear because he/she fails to appear for study visits without stating an intention to withdraw and did not respond to repeated attempts of contact, who did not experience graft loss or death from Day 1 and whose last day of contact was prior to study Month 60. Durable chimerism is defined as maintaining at least 50% donor T-cells measured in recipient blood. For FCR recipients, inability to wean immunosuppression is defined as not meeting the criteria (BPAR >1A, chimerism <50% T-cells of donor, no graft versus host disease and having stable renal function) to discontinue their antirejection medications. Inability to remain
Measure: Incidence of acute rejection, death, renal graft loss, and lost to follow-up between FCR001 recipients who did not achieve durable chimerism or the ability to wean or remain off immunosuppression vs. the control arm Time: Month 24, 36, and 60Description: Autologous hematopoietic stem cell transplantation for FCR001 recipients using their reserved frozen cells obtained prior to renal transplantation may be performed, only when medically warranted for safety reasons.
Measure: The incidence of autologous infusions in FCR001 recipients Time: Month 6, 12, 24, 36, and 60Description: Engraftment syndrome is a clinical condition which can occur in recipients of hematopoietic stem cell transplantation that is characterized by some or all of the following: fever, skin rash, pulmonary edema, weight gain, liver, renal dysfunction and encephalopathy. This syndrome typically presents at the time of neutrophil recovery after hematopoietic stem cell transplantation.
Measure: The incidence of engraftment syndrome in FCR001 recipients. Time: Month 6, 12, 24, 36, and 60Description: Blood component transfusions include platelets, packed red blood cells, plasma and blood-clotting factor.
Measure: The incidence of blood component transfusions in FCR001 recipients Time: Month 6, 12, 24, 36, and 60Description: Time to neutrophil and platelet recovery is defined as the time it takes absolute neutrophil count to recover to > 500 cells/µL and platelet count to recover to >50K from their depression following conditioning therapy in preparation of FCR001 recipients to receive FCR001 cell therapy.
Measure: The time to neutrophil and platelet recovery in FCR001 recipients. Time: Month 6, 12, 24, 36, and 60Description: Graft versus host disease (GvHD) occurs when the donor's T cells (the graft) view the patient's healthy cells (the host) as foreign, and attack and damage them. Acute and chronic GvHD will be reported as adverse events.
Measure: The incidence of acute and chronic Graft versus Host Disease (GvHD) in FCR001 recipients will be described Time: Month 6, 12, 24, 36, and 60Description: Donor chimerism is defined by > 50% donor T-cells measured in recipient blood.
Measure: The incidence of donor chimerism and level of chimerism by study visit in FCR001 recipients will be described Time: Month 6, 12, 24, 36, and 60Description: Freedom from immunosuppression is defined as the ability to discontinue anti-rejection medications and not having to restart any antirejection medication. Donor chimerism is defined by > 50% donor T-cells measured in recipient blood.
Measure: The correlation of donor chimerism with freedom from immunosuppression (IS) in FCR001 recipients will be described. Time: Month 6, 12, 24, 36, and 60Alphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on December 13, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
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