Controlling Hyperactive Immunity With Long-lived Lymphocytes

NCT07473154 | Recruiting Phase 1 DMC

• 2 other identifiers: QEL-005-CLN-012025-523971-46
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Systemic Sclerosis (SSc); Autoimmune Rheumatologic Disease; Diffuse Cutaneous Systemic Sclerosis; Rheumatoid Arthritis (RA)

Keywords

Regulatory T cells; Autologous; Genetically modified cells; Treg; Chimeric antigen receptor (CAR)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (19)

• D2TRA: Change from baseline in American College of Rheumatology (ACR) response criteria

  Week 4,8,12,24,38 and 52

• D2TRA: Change from baseline in a disease activity score-28 C-reactive protein (DAS28-CRP)

  Week 4,8,12,38 and 52

• D2TRA: Change from baseline in Health Assessment Questionnaire Disability Index

  Week 4,8,12,24,38 and 52

• D2TRA: Change from baseline in Ultrasound Outcome Measure in Rheumatology (OMERACT) score

  Week 12 and 52

• D2TRA: Clinical response status

  Week 12 and 52

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Dose escalation will involve 3 distinct dose level ranges. Each dose level will enrol at least 3 participants

Drug: QEL-005

Dose Expansion

EXPERIMENTAL

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

Interventions

QEL-005 DRUG

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.

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Quell Therapeutics Limited: lead

Study Sites (6)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

NOT YET RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

NOT YET RECRUITING

Guy's & St Thomas NHS Foundation Trust

London, United Kingdom

NOT YET RECRUITING

Royal Free London NHS Foundation Trust

London, United Kingdom

NOT YET RECRUITING

Newcastle Upon Tyne NHS Foundation Trust

Newcastle, United Kingdom

RECRUITING

University of Oxford - The Kennedy Institute

Oxford, United Kingdom

RECRUITING

MeSH Terms

Conditions

Scleroderma, Diffuse; Arthritis, Rheumatoid; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Quell Therapeutics Clinical Trials

CONTACT

+44(0)2070969012; contact@quell-tx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of two parts: (1) a dose escalation phase that includes three sequential cohorts receiving increasing dose levels, and (2) a dose expansion phase in which a selected dose level will be further evaluated.

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 16, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)