Actively Recruiting
Phase 1/2 Single-Arm Open-Label Trial Evaluating Safety and Feasibility of CRISPR-Cas9 Edited Donor Kidneys (HLA-A, HLA-B, CIITA Knockout) in Adult Kidney Transplant Recipients
Led by AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLC · Updated on 2025-07-08
90
Participants Needed
1
Research Sites
53 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new approach to kidney transplantation in adults with end-stage renal disease (ESRD) using donor kidneys genetically modified with CRISPR-Cas9 to reduce immune rejection. This trial focuses on disrupting key donor human leukocyte antigen (HLA) genes, including HLA-A, HLA-B, and CIITA, to lower the risk of graft rejection by making the kidney less recognizable to the recipient's immune system. The study aims to assess the safety and feasibility of this novel gene-editing method along with its impact on immune responses and graft function over one year after transplant. The trial involves transplanting donor kidneys edited ex vivo with CRISPR-Cas9 to knock out HLA class I heavy chains HLA-A and HLA-B and disable HLA class II expression through CIITA gene disruption. The gene-edited kidney is transplanted using standard surgical techniques, and participants receive usual immunosuppressive medications, which may be adjusted based on the edited kidney's lower immunogenicity. This is a single-arm study where about 90 adult participants will receive the experimental gene-edited kidney graft. Participants will be hospitalized for the transplant surgery and closely monitored afterward with frequent clinic visits. Assessments include tracking serious adverse events, graft survival at six months, acute rejection episodes, donor-specific antibody development, kidney function measured by eGFR, and immune cell responses over 12 months. Safety monitoring will also include checking for any off-target effects of gene editing and long-term transplant outcomes. Participants are followed for at least one year post-transplant to evaluate treatment effects and feasibility.
CONDITIONS
Brief Title
CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 16 to 85 years with end-stage renal disease who are candidates for kidney transplantation
- Eligible for transplant surgery with sufficient overall health for surgery and immunosuppression
- Suitable deceased-donor kidney available that is ABO blood type compatible and meets transplant criteria
- Able to understand and voluntarily sign informed consent and comply with study procedures
- Negative T and B cell crossmatch with donor organ prior to transplant
- Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and post-transplant period
- Men with partners of childbearing potential must agree to use contraception
- High immunologic risk patients, including those with panel reactive antibody levels above 80%, are eligible
- Willing and able to attend long-term follow-up visits at the study center or travel as needed
You will not qualify if you...
- Active severe infection that contraindicates transplantation or immunosuppression (e.g., untreated tuberculosis, uncontrolled HIV)
- Pregnancy or breastfeeding
- Need for multi-organ transplant simultaneously
- Severe co-morbidities increasing transplant risk (e.g., uncontrolled cardiovascular disease, severe liver dysfunction)
- Contraindications to immunosuppressive therapy
- Inability to follow study protocol due to psychiatric, cognitive, or social issues
- Prior participation in gene therapy or experimental transplant treatments
- Significant laboratory abnormalities posing added risk (e.g., severe leukopenia, coagulopathy)
- Donor kidney unsuitable for gene editing or transplant after retrieval
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for eligibility assessment and consent
Duration - Short period immediately prior to transplantation
The donor kidney undergoes ex vivo CRISPR-Cas9 gene editing to knock out specific HLA genes to reduce graft immunogenicity before transplantation.
No participant visits; gene editing occurs outside the body
Duration - Up to 2 weeks or until hospital discharge
Participants receive the gene-edited donor kidney through a surgical transplant procedure and receive standard peri-operative care with close monitoring during hospitalization.
Hospitalization for transplant surgery and immediate post-operative monitoring
Duration - Up to 12 months post-transplant
Participants are followed in clinic frequently after discharge to monitor transplant function, manage immunosuppression, and assess for any rejection or complications.
Weekly visits for up to 12 weeks, then regular follow-up visits up to 12 months
Trial Site Locations
Total: 1 location
1
Peking University Health Science Center (PKUHSC)
Beijing, Changping, China, 102206
Actively Recruiting
Research Team
A
Andrew R Linehan
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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