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

Liver Diseases Clinical Trial

— LIBERATE  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05234190
• Other study ID #: QEL-001-CLN-01
• Secondary ID: 2021-001379-18
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 21, 2022
• Est. completion date: March 2040

Study information

• Verified date: April 2024
• Source: Quell Therapeutics Limited
• Contact: Quell Therapeutics Clinical Trials
• Phone: +44(0)2070969012
• Email: contact[@]quell-tx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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body accept their donated liver and prevent their immune system from rejecting it once immune suppression is withdrawn.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: March 2040
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Liver Diseases
• Liver Failure
• Rejection; Transplant, Liver

Intervention

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.

Locations

Country	Name	City	State
Belgium	H. Saint Luc	Brussels
Belgium	Hopital Erasme	Brussels
Belgium	UZ Leuven	Leuven
Spain	H. Clinic Barcelona	Barcelona
Spain	Hospital Reina Sofia	Córdoba
Spain	G. Gergorio Maranon	Madrid
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	Royal Free London NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Quell Therapeutics Limited

Countries where clinical trial is conducted

Belgium,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess Safety Related Events	Incidence and severity of infections from treatment to Week 82.	Up to 82 weeks post infusion
Other	Presence of Replication Competent Lentivirus	Absence or presence of exposure to replication-competent lentivirus	up to 52 weeks post infusion
Primary	Safety and Tolerability	Incidence of protocol defined Dose Limiting Toxicities (DLTs).	28 Days post infusion
Primary	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
Secondary	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
Secondary	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
Secondary	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