Using long-lived immune cells to calm an overactive immune system
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 trial will try QEL-005, an autologous CD19-directed CAR-T regulatory cell therapy, to calm immune overactivity in adults with diffuse cutaneous systemic sclerosis or difficult-to-treat rheumatoid arthritis.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 16 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Quell Therapeutics Limited Industry-sponsored |
| Drugs / interventions | CAR-T, chimeric antigen receptor |
| Locations | 6 sites (Birmingham and 5 other locations) |
| Trial ID | NCT07473154 on ClinicalTrials.gov |
What this trial studies
QEL-005 is made from a participant's own white blood cells collected by leukapheresis, genetically modified ex vivo to express a CD19-targeted regulatory receptor, and returned by intravenous infusion. This open-label Phase 1/2, single-arm study uses a dose-escalation followed by dose-expansion design to characterize safety and tolerability and to collect preliminary clinical and biological activity data. Safety monitoring includes adverse event recording, laboratory tests, and vital signs, and secondary assessments will track disease-specific outcome measures and immune biomarkers. Participants will be followed long-term, including a planned 15-year follow-up for durability and late safety signals.
Who should consider this trial
Good fit: Adults with diffuse cutaneous systemic sclerosis or difficult-to-treat rheumatoid arthritis who meet the protocol's disease-specific criteria, have adequate blood, liver and kidney function, and are willing to undergo leukapheresis, IV infusion, contraception requirements, and long-term follow-up are the intended participants.
Not a fit: Patients with severe organ failure, active infections, inability to provide sufficient cells for manufacturing, or those unwilling to comply with vaccination, contraception, or long-term follow-up requirements may be ineligible or unlikely to benefit.
Why it matters
Potential benefit: If successful, QEL-005 could reduce autoimmune-driven disease activity and provide longer-lasting control of inflammation with potentially less dependence on broad immunosuppression.
How similar studies have performed: CD19-directed CAR-T cells have been highly successful in treating certain blood cancers, but CAR-T regulatory cell therapies for autoimmune diseases are a novel first-in-human approach with limited clinical precedent.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Birmingham and 5 other locations
- University Hospitals Birmingham NHS Foundation Trust — Birmingham, United Kingdom (Not_yet_recruiting)
- Leeds Teaching Hospitals NHS Trust — Leeds, United Kingdom (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)
Study contacts
- Study coordinator: Quell Therapeutics Clinical Trials
- Email: contact@quell-tx.com
- Phone: +44(0)2070969012
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.