NCT07298590
Not yet recruiting
Early Phase 1
An Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA CAR-NK (KN5601) in the Treatment of Relapsed and Refractory IgG4-related Disease (IgG4-RD)
InterventionsCD19/BCMA CAR NK
Overview
- Phase
- Early Phase 1
- Status
- Not yet recruiting
- Sponsor
- Changhai Hospital
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Incidence of Dose-Limiting Toxicity (DLT)
Overview
Brief Summary
A single arm, open-label pilot study is designed to determine the safety and effectiveness of CD19/BCMA CAR NK cells (KN5601) in patients with IgG4 related diseases.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects must be able to understand and provide informed consent and be willing to comply with study procedures and follow-up.
- •The age at the time of signing the informed consent must be at least 18 years old and no more than 70 years old.
- •Meet the 2020 Japanese criteria or ACR/EULAR IgG4-RD classification criteria.
- •Subjects with relapsed/refractory active IgG4-RD at screening on an IgG4-RD RI ≥4, simultaneously meeting the following definitions of relapse or refractory disease:
- •Definitions of relapse: subjects with IgG4-RD achieved remission after treatment but was active again before screening, and were classified as a high-risk group for recurrence assessed by assessment committee ;
- •Definitions of before screening: subjects had used glucocorticoids or glucocorticoids combined with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARDs) (including cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, elorimod, thalidomide, etc.), or at least one approved biologic agent (bDMARDs) (including rituximab, abatacept, etanercept, belimumab, etc.), or targeted synthetic (ts) DMARDs (including tofacitinib, upadacitinib, baricitinib, abrocitinib, deucravacitinib, etc.) for treatment, with a total treatment duration of ≥3 months, yet still in an active disease state, ineffective, intolerant, or experiencing relapse during glucocorticoid tapering.
- •No history of severe allergic reaction.
- •Female participants of childbearing age must have a negative pregnancy test upon enrollment in the study; indeterminate results will not be accepted.
- •Female subjects of childbearing age and male subjects with female partners of childbearing potential must agree to consistently use effective methods of birth control within 6 months after the last KN5601 infusion.
- •Echocardiography show that the heart structure is basically normal and the left ventricular ejection fraction (LVEF) is ≥55%; no obvious abnormalities are found on the electrocardiogram.
Exclusion Criteria
- •Presence of a condition other than IgG4-RD that (e.g., asthma) is likely to require systemic Glucocorticoids (GC) for disease control during the period of the trial.
- •Malignancy within 5 years (except successfully treated in situ cancer, resected squamous cell or basal cell carcinoma of the skin.).
- •During the screening visit, one of the following laboratory test values must be met, except for those caused by IgG4-RD.:
- •Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three times the upper limit of normal (ULN).
- •Total bilirubin \> two times the ULN unless caused by Gilbert's disease. Gilbert's disease with total bilirubin \> three times ULN.
- •White blood cell (WBC) count \<3.0×10⁹/L;
- •Absolute neutrophil count (ANC) \<1.5×10⁹/L;
- •Hemoglobin \<90 g/L;
- •Platelet count \<75×10⁹/L;
- •Estimated glomerular filtration rate (eGFR) ≤ 45 ml/(min·1.73m2).
Arms & Interventions
This study is a single-arm, open-label and single-center exploratory clinical study
Experimental
Intervention: CD19/BCMA CAR NK (Biological)
Outcomes
Primary Outcomes
Incidence of Dose-Limiting Toxicity (DLT)
Time Frame: up to 48 weeks
To characterize the safety of CD19/BCMA CAR NK Cells (KN5601) for IgG4 related diseases
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame: up to 48 weeks
To characterize the safety of CD19/BCMA CAR NK Cells (KN5601) for IgG4 related diseases
The percentage of disease remission (Remission is defined as IgG4-RD RI=0 after treatment and without the use of hormones
Time Frame: 24 weeks
To characterize the safety of CD19/BCMA CAR NK Cells (KN5601) for IgG4 related diseases
Secondary Outcomes
- Percentage of disease remission of IgG4-RD RI score compared with baseline(12, 24, 48 weeks)
- Percentage of complete response, partial response, and no change (NC)(12, 24, 48 weeks)
- Disease recurrence rate(24, 48 weeks after infusion)
- Physician Global Assessment (PhGA) compared with baseline(up to 48 weeks)
- Patient Global Assessment (PGA) compared with baseline(12, 24, 48 weeks)
- Disease-related Injury Score(12, 24, 48 weeks)
- Assessment of persistence of KN5601 after infusion(up to 48 weeks)
- Health Survey by Health Status Questionnaire (SF-36)(up to 48 weeks)
- Assessment of organ function compared with baseline based on MRl imaging(up to 48 weeks)
- Assessment of the affected tissues and organs compared with baseline based on CT imaging examination(up to 48 weeks)
Investigators
Study Sites (1)
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