Controlling Hyperactive Immunity With Long-lived Lymphocytes (CHILL)

Phase I/II Study of QEL-005 in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc) and in Patients With Difficult to Treat Rheumatoid Arthritis (D2TRA).

This study is a Phase 1/2, open-label clinical trial to test an experimental treatment called QEL-005 in adults with two autoimmune conditions: diffuse cutaneous systemic sclerosis (dcSSc) and difficult-to-treat rheumatoid arthritis (D2TRA). The main goals are to find out whether QEL-005 is safe, how well people tolerate it, and whether it may help reduce disease activity or improve symptoms.

QEL-005 is made from a participant's own white blood cells (autologous cells). These cells are collected and then changed in a laboratory using genetic methods to create specialized immune cells called CAR-T regulatory cells that target a protein on B cells called CD19. These modified cells are then given back to the participant by intravenous (IV) infusion.

To take part, eligible participants will first have a procedure called leukapheresis, where some of their white blood cells are removed from the blood. The study team will use these cells to manufacture QEL005. After QEL005 is ready, participants will receive an IV infusion of their modified cells, stay in hospital overnight for monitoring, and will then be followed closely in the clinic.

Throughout the trial, participants will have regular safety checks, which may include blood tests, imaging scans, questionnaires about symptoms and daily functioning, and biopsies taken from involved tissues, to help understand how QEL005 is working in the body. Detailed follow up will be for 1 year after QEL-005 infusion, and there is long-term follow up for a total of 15 years, which is standard for cell therapies. The information from this Phase 1/2 study will help determine an appropriate dose and dosing schedule of QEL005 for future studies.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Cutaneous Systemic Sclerosis; Rheumatoid Arthritis (RA); Autoimmune Rheumatologic Disease; Systemic Sclerosis (SSc)
• Intervention / Treatment: Drug: QEL-005

Detailed Description

This is a single-arm, open label, multicentre, Phase 1/2, first in human study of QEL005 in adult participants with diffuse cutaneous systemic sclerosis (dcSSc) or difficult to treat rheumatoid arthritis (D2TRA). QEL005 is an autologous chimeric antigen receptor regulatory T-cell (CAR-Treg) therapy directed against the CD19 marker found on B cells.

The primary objective of this study is to evaluate the safety and tolerability of single IV infusions of QEL005 across different dose levels in participants with dcSSc or D2TRA. Secondary and exploratory objectives include assessment of preliminary clinical efficacy (for example, changes in disease activity scores, skin involvement, or joint symptoms, as appropriate for each disease) and evaluation of biological activity (including effects on B cell populations, immune biomarkers, and other laboratory measures).

The study uses a dose escalation phase then a dose expansion phase. In the dose escalation phase, sequential cohorts of participants receive increasing doses of QEL005 under close safety monitoring. Safety assessments include recording of adverse events, vital signs and laboratory abnormalities.

QEL005 is manufactured from autologous leukapheresis material obtained at baseline. Participants undergo leukapheresis for collection of peripheral blood mononuclear cells, which are then genetically modified ex vivo to express a CD19directed CAR-T regulatory cell.

Over the course of the trial, participants will attend scheduled visits for clinical evaluations, laboratory tests, imaging studies, and patient reported outcome questionnaires, as well as tissue biopsies, to characterize the safety profile and to explore pharmacodynamic and immunologic effects of QEL005. There are detailed assessments over the first year following QEL-005 infusion, and then additional long-term follow up for 15 years, standard for cell therapy trials. Data from this Phase 1/2 trial will inform the recommended dose, regimen, and patient population for subsequent studies of QEL005 in autoimmune diseases.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Quell Therapeutics Clinical Trials; Phone Number: +44(0)2070969012; Email: contact@quell-tx.com

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • Not yet recruiting
    • University Hospitals Birmingham NHS Foundation Trust
    • Contact: Benjamin Fisher; Phone Number: 0121 627 8314; Email: ClinicalResearchFacilityEnquiries@uhb.nhs.uk
    • Principal Investigator: Benjamin Fisher
  • Leeds, United Kingdom
    • Recruiting
    • Leeds Teaching Hospitals NHS Trust
    • Principal Investigator: Francesco Del Galdo
    • Contact: Francesco Del Gado; Phone Number: 0113 392 4444; Email: leedscrf@nhs.net
  • London, United Kingdom
    • Not yet recruiting
    • Royal Free London NHS Foundation Trust
    • Contact: Voon Ong; Phone Number: 020 7472 6201; Email: rf.crf@nhs.net
    • Principal Investigator: Voon Ong
  • London, United Kingdom
    • Not yet recruiting
    • Guy's & St Thomas NHS Foundation Trust
    • Contact: Andrew Cope; Phone Number: 020 7188 7188; Email: gstt.crfadmin@nhs.net
    • Principal Investigator: Andrew Cope
  • Newcastle, United Kingdom
    • Recruiting
    • Newcastle Upon Tyne NHS Foundation Trust
    • Contact: John Isaacs; Phone Number: 0191 282 4444; Email: crf.admin@newcastle.ac.uk
    • Principal Investigator: John Isaacs
  • Oxford, United Kingdom
    • Recruiting
    • University of Oxford - The Kennedy Institute
    • Principal Investigator: Chris Buckley
    • Contact: Chris Buckley; Phone Number: 01865 612 600; Email: emcrf@ouh.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be at least 18 years of age at the time of signing the informed consent.
• Up to date vaccination status and no planned vaccinations for post 3 months infusion
• Adequate haematological, liver and renal function
• Willing to undergo annual influenza vaccination
• Willing to enter a 15-year follow-up
• Eastern Cooperative Oncology Group (ECOG) performance status grade < 3
• Able and willing to use a highly effective method of contraception
• Stable dose of steroid prior to screening

Specific inclusion criteria for participants with difficult to treat rheumatoid Arthritis (D2TRA) only:

• Diagnosis of Rheumatoid Arthritis (RA) per 2010 ACR-EULAR criteria
• Diagnosis of D2TRA per 2021 EULAR criteria
• Evidence of clinically active disease a defined by validated clinical or laboratory results consistent with standard definitions of active RA
• Evidence of inflammation in target joints used for the DAS28 CRP assessment

Specific inclusion criteria for participants with diffuse cutaneous systemic sclerosis (dcSSc) only:

• Diagnosis of dcSSc as per the 2013 ACR-EULAR criteria
• Serologically positive for antinuclear antibodies
• Failure to respond sufficiently to immunomodulatory disease modifying anti-rheumatic drugs (DMARDs).
• Skin involvement with a total modified Rodnan Skin Score of at least 15
• Evidence of lung fibrosis based on imaging or pulmonary function testing
• Evidence of active disease based on a validated SSc activity assessment

Exclusion Criteria:

• Presence of a significant medical condition(s), or clinically significant laboratory abnormality
• History or concern of autoimmune diseases other than those under study
• Active infection, or recurrent chronic infection requiring intervention
• Immunodeficiency or receiving immunoglobulin replacement therapy
• Past or current infection with hepatitis B or C, tuberculosis, syphilis, or HIV
• Clinically significant cardiac dysfunction or severe pulmonary impairment
• Use of investigational agents within a pre-defined period prior to study screening
• Received a previous cell therapy
• Received certain B cell related experimental therapies in a clinical trial with the past year
• Any solid organ, bone marrow or stem cell transplant
• History of malignancy in the past 5 years
• Receiving prohibited medication that cannot be stopped at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Dose escalation will involve 3 distinct dose level ranges. Each dose level will enrol at least 3 participants	Drug: QEL-005; QEL-005 is an autologous cell therapy that is composed of engineered regulatory T cells transduced with a lentiviral vector containing a CAR directed against the B cell marker CD19. Treatment will be given via an IV infusion.
Experimental: Dose Expansion; The dose selected for dose expansion will be based on safety and any relevant additional data emerging from the Dose Escalation phase	Drug: QEL-005; QEL-005 is an autologous cell therapy that is composed of engineered regulatory T cells transduced with a lentiviral vector containing a CAR directed against the B cell marker CD19. Treatment will be given via an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
D2TRA & SSc: Incidence of Protocol-Defined Dose Limiting Toxicities (DLTs) to Assess Safety and Tolerability (Dose Escalation Phase Only)	Assessment of safety and tolerability of QEL-005 during the Dose Escalation Phase, as measured by the incidence of protocol-defined dose limiting toxicities (DLTs).	up to 28 days post-infusion
D2TRA & SSc: Incidence and grade of treatment-emergent adverse events (TEAEs), adverse events (AEs) and adverse events of special interest (AESIs)	Assessment of safety and tolerability of D2TRA & SSc through the collection and evaluation of the incidence and severity grades of all TEAEs, AEs, and AESIs using the Common Terminology Criteria for Adverse Events (CTCAE)	From time of signing the informed consent form (ICF) through to week 52
D2TRA & SSc: Incidence of clinically significant abnormalities in safety laboratory parameters, electrocardiogram (ECG) findings, and vital signs	Evaluation of safety through the assessment of clinically significant abnormalities in safety laboratory parameters, ECG findings, and vital signs.	Up to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
D2TRA: Change from baseline in American College of Rheumatology (ACR) response criteria	Assessment of absolute values and change from baseline using a validated functional assessment tool that incorporates patient-reported measures of physical function and clinician-reported evaluations of disease activity, joint involvement, and pain	Week 4,8,12,24,38 and 52
D2TRA: Change from baseline in a disease activity score-28 C-reactive protein (DAS28-CRP)	Assessment of absolute values and change from baseline using a validated composite clinical disease activity score that incorporates clinician-reported joint assessments, patient-reported disease activity, and laboratory or physiological indicators of inflammation	Week 4,8,12,38 and 52
D2TRA: Change from baseline in Health Assessment Questionnaire Disability Index	Assessment of absolute values and change from baseline in a standardised patient reported quality of life questionnaire evaluating overall disease impact	Week 4,8,12,24,38 and 52
D2TRA: Change from baseline in Ultrasound Outcome Measure in Rheumatology (OMERACT) score	Changes in standardised imaging score assessing synovitis and synovial vascularity in predefined joint.	Week 12 and 52
D2TRA: Clinical response status	Proportion of participants achieving predefined levels of disease activity improvements and functional improvements	Week 12 and 52
D2TRA & SSc: Use of additional background disease modifying therapy	Need for escalation of background disease modifying therapy above permitted baseline medication	Week 12 and 52
D2TRA: Cumulative steroid exposure	Total systemic steroid dose received over specified intervals	Baseline to week 12 and baseline to week 52
D2TRA: Ability to reduce glucocorticoid dose	Proportion of participants able to reduce systemic glucocorticoid use below a predefined daily threshold	Up to week 52
D2TRA & SSc: Change from baseline in autoantibodies	Evaluation of change in blood levels of disease related autoantibodies	Baseline to week 52
D2TRA & SSc: Presence of replication competent viral vector	Assessment of detectable replication competent viral vector in blood	Week 52
SSc: Change From Baseline in a Modified Rodnan Skin Score (mRSS)	Assessment of absolute values and change from baseline in a validated, standardised skin involvement assessment score evaluating the extent and severity of cutaneous involvement in systemic sclerosis.	Week 12,24,38 and 52
SSc: Change from baseline in Digital ulcers	Number of digital ulcers	Week 12, 24, 38 and 52
SSc: Change From Baseline in a Standardised Lung Function Assessment Score	Assessment of absolute values and change from baseline using a validated, standardized lung function assessment score that evaluates pulmonary functional capacity	Week 12, 24, 38 and 52
SSc: Change From Baseline in a Standardised High Resolution Computed Tomography (HRCT) Based Pulmonary Fibrosis Assessment Score	Assessment of absolute values and change from baseline in a validated, standardised HRCT based scoring system of interstitial lung disease, quantifying the extent and severity of pulmonary fibrosis.	Week 24 and 52
SSc: Change From Baseline in a Standardised Positron Emission Tomography (PET) Based Pulmonary Fibrosis Assessment Score	Assessment of absolute values and change from baseline in a validated, standardised PET based assessment of fibroblast activation and fibrosis activity in predefined lung regions.	Week 24 and 52
SSc: Change from baseline in Health Assessment Questionnaire Disability Index	Assessment of absolute values and change from baseline in a standardised patient reported quality of life questionnaire evaluating overall disease impact	Week 12, 24, 38 and 52
SSc: Change From Baseline in the EUropean Scleroderma Trials And Research group (EUSTAR) Activity Index	Assessment of absolute values and change from baseline in a validated composite clinical disease activity assessment score used to evaluate systemic sclerosis disease activity.	Week 12, 24, 38 and 52
SSc: Change From Baseline in the Sclerderma Clinical Trial Consortium (SCTC) Disease Damage Index	Assessment of absolute values and change from baseline in a validated disease damage assessment score used to evaluate longer-term organ involvement.	Week 12, 24, 38 and 52
Change from Baseline in the European Alliance of Associations for Rheumatology Systemic Sclerosis Impact of Disease (EULAR ScleroID)	Assessment of absolute values and change from baseline in a validated patient-reported outcome questionnaire designed to measure the overall impact of systemic sclerosis on patients' daily function and quality of life.	Week 12, 24, 38 and 52

Collaborators and Investigators

• Sponsor: Quell Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Autologous; Treg; Regulatory T cells; Chimeric antigen receptor (CAR); Genetically modified cells
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Arthritis, Rheumatoid
• Other Study ID Numbers: QEL-005-CLN-01; 2025-523971-46 (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