Kidney Disease
Conditions
Brief summary
This Phase I pilot study will evaluate the safety, and tolerability of darTreg infusion for adult, de novo, living donor renal transplant recipients.
Detailed description
A single-center, open-label, dose-escalation pilot trial of a single infusion of darTregs in two dosing cohorts. This study is an independent single-center clinical trial. However, the organizational and mechanistic infrastructure of the study will be provided by the ONE Study project, a European Union funded collaborative project, whose objective is to assess distinct purified hematopoietic immunoregulatory cells as clinical therapies in solid organ transplantation. This study is one of multiple clinical trials within the framework of The ONE Study project, based on the same general design.
Interventions
DRUGdarTreg infusion
The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients. sBc production for darTreg manufacturing for the second subject in each cohort may be initiated but the second subject may not undergo leukapheresis until the safety review is complete. Once the last subject in the first cohort reaches week 4 post-infusion, the DSMB will conduct a thorough review of all available data to make a determination about proceeding with additional patients at the lower dose or proceeding to the second dosing cohort. sBc production for darTreg manufacturing for the subsequent subject may be initiated but the patient may not undergo leukapheresis until the DSMB( Data Safety and Monitoring Board ) has approved enrollment of subsequent subjects.
Sponsors
Seventh Framework Programme
University of California, San Francisco
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
(organ donor eligibility) 1. Eligible for live kidney donation 2. At least 18 years of age 3. An ABO blood type compatible with the organ recipient 4. Willing and able to provide a blood sample for The ONE Study IM (Immune Monitoring) Subproject 5. Willing to provide personal and medical/biological data for the trial analysis 6. Eligible to give blood for B cell source prior to organ donation 7. Signed and dated written informed consent\*. \*For subjects unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the subject has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the subject. In signing the donor information sheet/informed consent form (DIS/ICF), organ donors agree to undergo phlebotomy to provide donor B cells for the production of darTreg, to provide a blood sample for the IM Subproject, and permit access to their medical records for the collection of specified demographic and medical/biological data for the trial. Organ Recipient eligibility: A prospective kidney transplant recipient is eligible for enrollment into the study if all of the following inclusion criteria apply: 1. Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor 2. At least 18 years of age 3. Able to commence the immunosuppressive regimen at the protocol-specified time point 4. Willing and able to participate in The ONE Study IM and HEC (Health-Economics Subproject) subprojects 5. Adequate venous access to support leukapheresis 6. Signed and dated written informed consent\*. * For patients unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the patient has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the patient.
Exclusion criteria
(organ donor) If a prospective donor fulfills any of the following criteria, they are ineligible for the trial: 1. Genetically identical to the prospective organ recipient at the HLA (human leukocyte antigen) loci (0-0-0 mismatch) 2. CMV-positive and donating to a CMV-negative recipient 3. Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation 4. Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel 5. Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of biopsy-confirmed acute rejection (BCAR) following renal transplantation. | 60 weeks post renal transplantation | Explore the immunomodulatory potential, safety and tolerability of a single infusion of darTregs as adjunct immunosuppressive treatment through the incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks following renal transplantation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection | 60 weeks post renal transplantation | — |
| Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections especially CMV (cytomegalovirus ), EBV (Epstein-Barr virus) and polyoma virus | 60 weeks post renal transplantation | — |
| Incidence of neoplasia | 60 weeks post renal transplantation | — |
| Incidence of patients treated for subclinical acute rejection | 60 weeks post transplantation | — |
| Time to first acute rejection episode | 60 weeks post renal transplantation | — |
| Severity of acute rejection episodes | 60 weeks post renal transplantation | severity of acute rejection episodes based on response to treatment and histological scoring |
| Total immunosuppressive burden at 60 weeks post-transplantation | 60 weeks post renal transplantation | Total immunosuppressive burden assessed at last study visit |
| Prevention of chronic graft dysfunction (chronic rejection or IF/TA) | 60 weeks post renal transplantation | chronic graft dysfunction assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures |
| Avoidance of drug-related complications by immunosuppressant reduction | 60 weeks post renal transplantation | Assessed by the incidence of reported adverse drug reactions |
| Biochemical disturbances caused by cell infusion | 1 week | Assessed by Incidence of acute toxicities associated with infusion of the cell product |
Other
| Measure | Time frame |
|---|---|
| A Health-Economics Subproject will evaluate the health-related qualify-of-life of trail patients using patient-reported outcome measures | 60 weeks post transplantation |
| incidence of autoimmune disorders | 60 weeks post transplantation |
| Incidence of malignancies arising directly from darTreg infusion | 60 weeks |
Countries
United States
Outcome results
None listed