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.
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
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
Sequential
QEL-005
DrugQEL-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.
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).
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)
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.
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
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
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
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.
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