Clinical trial NCT05234190: Safety and Clinical Activity of QEL-001 in A2-mismatch Liver Transplant Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Rejection; Transplant, Liver
Liver Failure
Liver Diseases
Keywords: Regulatory T cells
Chimeric Antigen Receptor
Autologous
Genetically modified cells
Lead sponsor: Quell Therapeutics Limited
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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body accept their donated liver and prevent their immune system from rejecting it once immune suppression is withdrawn.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 28 Days post infusion
measure: Long-term safety
timeFrame: Day of infusion through to Week 82 and up to 15 years post infusion
Secondary outcomes:
measure: Immunosuppression related outcome
timeFrame: 2 months and 1 year post withdrawal of immune suppression
measure: Tolerance related outcome
timeFrame: 1 year following immune suppression withdrawal
measure: Composite efficacy failure outcome
timeFrame: 1 year following immune suppression withdrawal
Other outcomes:
measure: Assess Safety Related Events
timeFrame: Up to 82 weeks post infusion
measure: Presence of Replication Competent Lentivirus
timeFrame: up to 52 weeks post infusion
Locations:
city: Brussels
country: Belgium
facility: H. Saint Luc
city: Brussels
country: Belgium
facility: Hopital Erasme
city: Leuven
country: Belgium
facility: UZ Leuven
city: Barcelona
country: Spain
facility: H. Clinic Barcelona
city: Córdoba
country: Spain
facility: Hospital Reina Sofia
city: Madrid
country: Spain
facility: G. Gergorio Maranon
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
References: