Safety and Clinical Activity of QEL-001 in A2-mismatch Liver Transplant Patients (LIBERATE)

A Single-arm, Open-label, Multi-center, Phase I/II Study Evaluating the Safety and Clinical Activity of QEL-001, an Autologous CAR T Regulatory Cell Treatment Targeting HLA-A2, in HLA-A2/ A28neg Patients That Have Received an HLA-A2pos Liver Transplant.

The purpose of this study is to evaluate the safety and tolerability of QEL-001 in the prevention of liver transplant rejection following immunosuppression withdrawal. QEL-001 is a product made from a patients own cells, which are genetically modified and designed to help the transplant recipient's body accept their donated liver and prevent their immune system from rejecting it once immune suppression is withdrawn.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Diseases; Liver Failure; Rejection; Transplant, Liver
• Intervention / Treatment: Drug: QEL-001

Detailed Description

This study is a multicenter, first-in-human, open-label, single-arm study of an autologous CAR T regulatory (CAR-Treg) in HLA-A2 mismatched liver transplant recipients. The aim is for the CAR-Tregs to be activated on recognition of HLA-A2 antigens present on the donated liver and subsequently induce and maintain immunological tolerance to the organ.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Hopital Erasme
  • Brussels, Belgium
    • H. Saint Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
• Spain
  • Barcelona, Spain
    • H. Clinic Barcelona
  • Córdoba, Spain
    • Hospital Reina Sofía
  • Madrid, Spain
    • G. Gergorio Maranon
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent.
• Subject who are HLA A2/A28 negative who have received HLA A2-mismatch liver transplant 12 months to 5 years prior to study entry.
• Able and willing to use contraception.
• Be on stable maintenance of immunosuppression for at least 12 weeks prior to study entry.

Exclusion Criteria:

• Severe cardiac, respiratory disease or any other major organ dysfunction.
• Subjects with prior non-liver solid organ or hematopoietic stem cell transplant.
• Known hypersensitivity to study medication ingredients, protocol defined immunosuppressive medications, or a significant allergic reaction to any drug.
• Positive serology for human immunodeficiency virus (HIV), active or latent tuberculosis (TB) or other clinically active local or systemic infection.
• Use of investigational agents within 3 months of screening.
• Subjects with history of autoimmune disease requiring use of immunosuppression or biologics within 24 months prior to study entry.
• Subject with history of malignancy in the past 5 years.
• Medical or social condition that is not compatible with adequate study follow-up and any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study.

• Protocol defined laboratory value for the following parameters:

  • Alanine aminotransferase (ALT) and either alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT),
  • Kidney function e.g. eGFR,
  • White blood cells,
  • Hemoglobin,
  • Platelets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group	Drug: QEL-001; QEL-001 is an autologous therapy that is composed of engineered regulatory T cells transduced with a lentiviral vector containing a CAR directed against HLA-A2. Treatment will be given via an IV infusion.; Other Names: HLA-A2 CAR-Treg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term safety	Incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.	Day of infusion through to Week 82 and up to 15 years post infusion
Safety and Tolerability	Incidence of protocol defined Dose Limiting Toxicities (DLTs).	28 Days post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunosuppression related outcome	Ability to withdraw immunosuppression (IS) as measured by the percentage of subjects who have stable Liver Function Tests and are IS free at two months and at one year following IS withdrawal.	2 months and 1 year post withdrawal of immune suppression
Tolerance related outcome	Ability to achieve operational tolerance as measured by the proportion of subjects meeting the clinical, biochemical and histological operational tolerance criteria at one year following IS withdrawal.	1 year following immune suppression withdrawal
Composite efficacy failure outcome	Proportion of subjects with composite event: acute rejection (AR), biopsy proven acute rejection (BPAR), reintroduction of IS or graft loss.	1 year following immune suppression withdrawal

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Safety Related Events	Incidence and severity of infections from treatment to Week 82.	Up to 82 weeks post infusion
Presence of Replication Competent Lentivirus	Absence or presence of exposure to replication-competent lentivirus	up to 52 weeks post infusion

Collaborators and Investigators

• Sponsor: Quell Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Actual): February 25, 2026
• Study Completion (Estimated): September 1, 2040

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Autologous; Chimeric Antigen Receptor; Regulatory T cells; Genetically modified cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Behavior; Social Behavior; Liver Diseases; Liver Failure; Rejection, Psychology
• Other Study ID Numbers: QEL-001-CLN-01; 2021-001379-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No