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

Primary Purpose

Rejection; Transplant, Liver, Liver Failure, Liver Diseases

Status

Recruiting

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

QEL-001

About this trial

This is an interventional treatment trial for Rejection; Transplant, Liver focused on measuring Regulatory T cells, Chimeric Antigen Receptor, Autologous, Genetically modified cells

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent.
Subject who 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.
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.

Sites / Locations

Queen Elizabeth Hospital
Cambridge University Hospitals NHS Foundation Trust
Royal Free London NHS Foundation Trust
King's College Hospital NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment group

Arm Description

Outcomes

Primary Outcome Measures

Safety and Tolerability

Safety and tolerability of QEL-001 infusion evaluated by incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.

Long-term safety

Incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.

Secondary Outcome Measures

Immunosuppression related outcome

Ability to withdraw immunosuppression (IS) as measured by the proportion of subjects being IS free at two months and at one year following IS withdrawal.

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.

Composite efficacy failure outcome

Proportion of subjects with composite event: acute rejection (AR), biopsy proven acute rejection (BPAR), reintroduction of IS or graft loss.

Long-term clinical activity outcome

Overall survival proportion of subjects

Full Information

NCT ID

NCT05234190

First Posted

February 1, 2022

Last Updated

December 22, 2022

Sponsor

Quell Therapeutics Limited

1. Study Identification

Unique Protocol Identification Number

NCT05234190

Brief Title

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

Acronym

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.

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 21, 2022 (Actual)

Primary Completion Date

June 2025 (Anticipated)

Study Completion Date

March 2039 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Quell Therapeutics Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rejection; Transplant, Liver, Liver Failure, Liver Diseases

Keywords

Regulatory T cells, Chimeric Antigen Receptor, Autologous, Genetically modified cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

QEL-001

Other Intervention Name(s)

HLA-A2 CAR-Treg

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety and Tolerability

Description

Safety and tolerability of QEL-001 infusion evaluated by incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.

Time Frame

28 Days post infusion

Title

Long-term safety

Description

Incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.

Time Frame

Day of infusion through to Week 82 and up to 15 years post infusion

Secondary Outcome Measure Information:

Title

Immunosuppression related outcome

Description

Ability to withdraw immunosuppression (IS) as measured by the proportion of subjects being IS free at two months and at one year following IS withdrawal.

Time Frame

Week 38 and Week 82

Title

Tolerance related outcome

Description

Time Frame

Week 82

Title

Composite efficacy failure outcome

Description

Proportion of subjects with composite event: acute rejection (AR), biopsy proven acute rejection (BPAR), reintroduction of IS or graft loss.

Time Frame

Day of infusion through to Week 82

Title

Long-term clinical activity outcome

Description

Overall survival proportion of subjects

Time Frame

Up to 15 years post infusion

Other Pre-specified Outcome Measures:

Title

Assess Safety Related Events

Description

Incidence and severity of infections from treatment to Week 82.

Time Frame

Up to 82 weeks post infusion

Title

Presence of Replication Competent Lentivirus

Description

Absence or presence of exposure to replication-competent lentivirus

Time Frame

up to 52 weeks post infusion

10. Eligibility

Sex

All

Gender Based

Yes

Gender Eligibility Description

Women of childbearing potential: negative pregnancy test

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent. Subject who 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Quell Therapeutics Clinical Trials

Phone

+44(0)2070969012

contact@quell-tx.com

Facility Information:

Facility Name

Queen Elizabeth Hospital

City

Birmingham

Country

United Kingdom

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Diana Hull

First Name & Middle Initial & Last Name & Degree

Shaida Begum

First Name & Middle Initial & Last Name & Degree

James Ferguson, MBChB, MRCP, MD, FRCP

Facility Name

Cambridge University Hospitals NHS Foundation Trust

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ann-Marie O'sullivan

First Name & Middle Initial & Last Name & Degree

Kourosh Saeb-Parsy, MA MB BChir FRCS PhD

First Name & Middle Initial & Last Name & Degree

Ben Uttenthal

Facility Name

Royal Free London NHS Foundation Trust

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Aileen Marshall, MBChB (Hons) and PhD

First Name & Middle Initial & Last Name & Degree

Neil Halliday

Facility Name

King's College Hospital NHS Foundation Trust

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bernadette Solis

First Name & Middle Initial & Last Name & Degree

Alberto Sanchez Fueyo, MD, PhD

First Name & Middle Initial & Last Name & Degree

Alison Taylor, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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