NCT07053488 CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection

Eligibility & Interventions

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.

This trial targets 90 participants in total. It began in 2025-06-01 with a primary completion date of 2027-12-18.

Brief Summary

This early-phase clinical trial will assess the use of ex vivo CRISPR-Cas9 genome editing on donor liver grafts to reduce immunogenicity before transplantation. Donor livers will have HLA-A and HLA-B genes knocked out, and HLA class II expression disabled (by targeting the CIITA transactivator gene), aiming to create a "hypoimmunogenic" organ less prone to rejection. The edited liver is then transplanted into patients with end-stage liver disease. The primary focus is on safety and feasibility - determining whether a CRISPR-edited liver can be transplanted successfully and function normally - as well as evaluating reductions in immune response (acute rejection, anti-donor T cell activation) and graft function over time.

Eligibility Criteria

Inclusion Criteria: * Adults aged 16-85 (inclusive) with end-stage liver disease or acute liver failure who are eligible for liver transplantation. * Require a liver transplant and have been allocated a donor liver graft (from a deceased donor) that will be used in the study after gene editing. * No immediately available fully HLA-matched donor (since the study targets patients who would otherwise receive an HLA-mismatched organ; standard allocation generally does not consider HLA matching for liver, so most patients will qualify). * Medically suitable for transplant surgery and able to tolerate standard immunosuppressive therapy (no contraindications to transplant such as uncontrolled infection or other active serious disease that would preclude surgery). * Informed Consent: Able to understand the investigational nature of the trial and provide written informed consent. Patients (and their legal representatives if applicable) must consent to the use of a genetically modified organ and to long-term follow-up including multiple biopsies and immune monitoring. * Willingness to comply with all study procedures and availability for the duration of follow-up (including frequent monitoring visits). Exclusion Criteria: * Active uncontrolled infection (e.g., sepsis, active tuberculosis) that would severely increase transplant risk or confound interpretation of immune-related outcomes. * Uncontrolled HIV or chronic viral infections that are not well-managed. (Note: Patients with hepatitis B or C may be included if adequately treated or under control, as these are common in liver failure, but such patients should not have active, replicating virus at transplant if possible.) * Multi-organ transplant requirement: Patients needing more than a liver alone (e.g., liver-kidney dual transplant) are excluded, as the trial is only evaluating single organ (liver) outcomes. * Pregnancy or breastfeeding: Female participants of childbearing potential must have a negative pregnancy test prior to transplant and must agree to use effective contraception. The effects of a gene-edited organ transplant on a fetus/infant are unknown, and immunosuppressive drugs can also harm a pregnancy. * Severe concurrent illness not related to liver disease that would limit survival to \<1 year or make the patient an unsuitable candidate (e.g., advanced heart failure, uncontrolled diabetes with complications, etc.). * Allergy or hypersensitivity to study-related products: If any components used in the ex vivo gene editing (such as a specific vehicle or enzyme) have known severe allergies in the recipient, they will be excluded. (For instance, although unlikely, if a patient had a documented severe immune reaction to Streptococcus pyogenes Cas9 or similar proteins, they would not be enrolled.) * Inability to follow the protocol or comply with follow-up: this includes psychiatric, social or logistical factors that would prevent adhering to the intense monitoring schedule (for example, lack of reliable transportation or support).

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