Kidney Transplantation
Conditions
Keywords
Regulatory T cells, Treg adoptive cell transfer (TRACT), Kidney Transplantation, Graft Rejection, Autologous cell therapy, End stage renal disease, Prevention of organ transplant rejection, Tregs, Reduced immunosuppression
Brief summary
The goal of this multi-national, multi-center, open-label, randomized Phase 2 trial is to determine the safety and efficacy of administering expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients. Enrolled subjects will be randomized to one of 2 study arms: Arm 1 subjects will receive standard of care immunosuppression Arm 2 subjects will receive initial standard of care (SOC) immunosuppression and a single infusion of TRK-001. Three months after the transplant, Arm 2 subjects may be able to begin reducing their immunosuppression medication to a 1-drug regimen. The primary outcome measures of trial are to evaluate several components indicating immunologic problems with the transplanted organ at 1-year post-transplant and to evaluate the ability for the study subjects given TRK-001 to wean to a 1-drug immunosuppression regimen. All enrolled subjects will be followed for 5 years post-transplant.
Detailed description
This is a prospective, multi-national, multi-center, open-label, randomized Phase 2 trial to determine the safety and efficacy of administering autologous expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients. All subjects will be followed for 5 years post-transplant, comprising of a 2-year post-transplant follow-up period and a 3-year surveillance period. Subjects with end-stage renal disease undergoing a living donor kidney transplant will be enrolled into the trial as follows: Arm 1 SOC: Standard of care immunosuppression (N=14) Arm 2 TRACT/MONO: TRK-001 and initial SOC immunosuppression weaned to monotherapy (N=20) At Month 3 post-transplant, Arm 2 subjects will be further randomized prior to weaning to either mTOR or CNI monotherapy as follows: Arm 2A: TRACT/MONO mTOR (N=10) or Arm 2B: TRACT/MONO CNI (N=10)
Interventions
DRUGArm 1: SOC (mTOR + CNI)
Subjects randomized to Arm 1 will remain on standard dual-immunosuppression therapy (CNI and mTOR) throughout the trial.
BIOLOGICALArm 2A: TRACT/MONO mTOR
All subjects will be prescribed standard of care (SOC) immunosuppressive agents. Subjects randomized to Arm 2 will be maintained on the prescribed SOC immunosuppression (tacrolimus + sirolimus or everolimus) and have a single intravenous infusion of autologous, expanded Tregs (TRK-001) at Day +53 to +67 post-transplant. At Month 3 post-transplant, Arm 2 subjects will be further randomized to receive either: * Arm 2A: mTOR monotherapy or * Arm 2B: CNI monotherapy. These subjects will transition to the assigned 1-drug immunosuppression regimen beginning at Month 3 post-transplant. Weaning must be completed by 12 months post-transplant. Subjects in Arm 2 will undergo leukapheresis to collect peripheral blood mononuclear cells required for the cellular product.
BIOLOGICALArm 2B: TRACT/MONO CNI
All subjects will be prescribed standard of care (SOC) immunosuppressive agents. Subjects randomized to Arm 2 will be maintained on the prescribed SOC immunosuppression (tacrolimus + sirolimus or everolimus) and have a single intravenous infusion of autologous, expanded Tregs (TRK-001) at Day +53 to +67 post-transplant. At Month 3 post-transplant, Arm 2 subjects will be further randomized to receive either: * Arm 2A: mTOR monotherapy or * Arm 2B: CNI monotherapy. These subjects will transition to the assigned 1-drug immunosuppression regimen beginning at Month 3 post-transplant. Weaning must be completed by 12 months post-transplant. Subjects in Arm 2 will undergo leukapheresis to collect peripheral blood mononuclear cells required for the cellular product.
Sponsors
Singulera Therapeutics Inc.
Taiwan Bio Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
All inclusion criteria must be met prior to randomization. 1. Males or females aged 18-65 years as of the date of informed consent who will undergo a single organ, living donor kidney transplant. 2. Donor aged 18-65 years as of the date of organ donation. A certain degree of HLA matching between the donor and the recipient is not required. 3. Blood type compatibility between recipient and donor must be established as follows. Recipient A to Donor A or O; Recipient B to Donor B or O; Recipient AB to Donor A, B, AB, or O; Recipient O to Donor O. 4. No prior organ transplant of any kind. 5. Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the trial. A list of the medically acceptable methods of contraception are listed in the informed consent document. 6. Male patients must agree to use birth control following the initiation of standard-of-care immunosuppression and for a minimum of 6 months following kidney transplant. 7. Subjects (recipients) must be able to understand the consent form and give written informed consent prior to any trial procedure. 8. If donor informed consent is required by IRB/IEC, donor must be able to understand the consent form and give written informed consent prior to any trial procedure. Note: Donor informed consent is required for donors participating in the research assay collections.
Exclusion criteria
Based on SOC Pre-Transplant Evaluation The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of de novo donor-specific antibodies | Month 12 Post-transplant | A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including the development of de novo donor-specific antibodies. |
| Biopsy-proven acute rejection | Month 12 Post-transplant | A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including biopsy-proven acute rejection. |
| Biopsy-proven subclinical rejection | Month 12 Post-transplant | A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including biopsy-proven subclinical rejection. |
| Development of significant (2+) interstitial fibrosis/tubular atrophy | Month 12 Post-transplant | A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including the development of significant (2+) interstitial fibrosis/tubular atrophy. |
| Successful taper to monotherapy (Arm 2) | Month 12 Post-transplant | A primary outcome measure for this study is to evaluate the ability for Arm 2 subjects to successfully taper to monotherapy by one-year post-transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Successful maintenance of monotherapy (Arm 2) | Month 24 Post-transplant | A secondary outcome measure for this study is to evaluate the ability for Arm 2 subjects to successfully maintain monotherapy through two-years post-transplant. |
| Development of de novo donor-specific antibodies | To Month 60 Post-transplant | A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including the development of de novo donor-specific antibodies. |
| Biopsy-proven acute rejection | To Month 60 Post-transplant | A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including biopsy-proven acute rejection. |
| Biopsy-proven subclinical rejection | To Month 60 Post-transplant | A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including biopsy-proven subclinical rejection. |
| Development of significant (2+) interstitial fibrosis/tubular atrophy | To Month 60 Post-transplant | A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including the development of significant (2+) interstitial fibrosis/tubular atrophy. |
| Graft loss | To Month 60 Post-transplant | A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including graft loss. Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation. |
| Malignancy | To Month 60 Post-transplant | A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including malignancy. |
| Infections | To Month 60 Post-transplant | A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including infections (bacterial, viral, fungal). |
| Metabolic anomalies | To Month 60 Post-transplant | A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including metabolic anomalies (e.g., diabetes mellitus, metabolic syndrome, hyperthyroidism, hypothyroidism). |
| Death (all cause) | To Month 24 Post-transplant | A secondary outcome measure for the study is to evaluate the incidence and timing of a composite endpoint of immunologic events against the allograft, where a failure is defined as patient- experienced immunologic event, including all cause death. |
| Quality of Life Measures by using KDQOL-SF | To Month 60 Post-transplant | The KDQOL-SF is an assessment tool designed for individuals with kidney disease to measure the impact of kidney disease and its treatment on a patient's quality of life. |
| Quality of Life Measures by using EQ-5D-5L | To Month 60 Post-transplant | The EQ-5D-5L is a standardized measurement tool to evaluate health status. The questionnaire has a descriptive section and a visual analog scale. |
| Safety- Adverse Events | To Month 60 Post-transplant | Incidence of adverse events |
Countries
Taiwan, United States
Contacts
CONTACTSusan B Murray
CONTACTErwin Teng
Outcome results
None listed