ClinicalTrials.gov record NCT07298590
An Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA CAR-NK in the Treatment of Relapsed and Refractory IgG4-related Disease
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)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This is an early-phase, single-arm, open-label study testing CD19/BCMA CAR‑NK cell therapy (KN5601) in adults with relapsed or refractory active IgG4‑related disease. Participants receive short lymphodepletion (fludarabine and cyclophosphamide) followed by multiple dose‑escalation infusions of CAR‑NK cells and are followed for safety and disease measures. The study aims to collect safety data and early measures of disease response over weeks to months.
What it is studying. The study is measuring the safety of CD19/BCMA CAR‑NK cell infusions (including dose‑limiting toxicities and treatment‑emergent adverse events) and collecting early evidence on disease response and remission, organ assessments, patient and physician global assessments, and how long the CAR‑NK cells persist in blood.
What the researchers hope to learn. To characterize the safety profile of KN5601 (CD19/BCMA CAR‑NK) in IgG4‑RD (incidence of DLTs and adverse events) and to gather preliminary data on remission rates, response categories, disease recurrence, organ function by imaging, patient/physician assessments, quality‑of‑life measures, and persistence of the CAR product.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Biological
- CD19/BCMA CAR NK
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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.
- Pulmonary function: No severe lung disease, SpO2 ≥ 92%.
- All subjects' eligibility for enrollment must be confirmed by an independent Assessment Committee (AC) (the committee consists of independent data monitors and clinical experts separate from the study). They will review the eligibility of each patient based on the scores entered at screening, as well as brief descriptions provided by the investigators regarding the supporting diagnosis, scores, and the patient's clinical status in relation to enrollment criteria..
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).
- Evidence suggests the presence of another uncontrolled disease, which the investigator has determined may affect the subject's participation in the trial.
- Active infection requiring hospitalization or treatment with systemic antimicrobial agents within the 30 days prior to treatment allocation/randomization.
- Received rituximab or other B-cell depleting therapies within 6 months prior to the baseline visit, unless B cells have recovered (B-cell recovery is defined as peripheral blood B-cell count ≥ the lower limit of normal reference range or returned to pre-treatment levels)。
- The use of supplemental oxygen at baseline.
- During the screening visit or within 90 days prior to the screening visit: T-SPOT positive. If the result is indeterminate, the T-SPOT must be repeated (using the same or a different T-SPOT) and shown as negative.
- During screening visits, individuals with a history of chronic infection or serological evidence, including:
- Human immunodeficiency virus infection;
- Hepatitis B as indicated by surface antigen or hepatitis B core antibody positivity;
- Hepatitis C as indicated by anti-hepatitis C antibody positivity; if a participant is Hepatitis C antibody positive, they will be eligible to participate in the study if he/she is negative for viral load at screening.
- Planned vaccination with live vaccines during the trial.
- Participant is pregnant or breastfeeding, or planning a pregnancy while enrolled in the study.
- IgG4-RD that is dominated primarily by advanced fibrotic lesions. Specifically, participants whose disease manifestations consist only of
- retroperitoneal fibrosis,
- fibrosing mediatinitis,
- sclerosing mesenteritis, and
- Riedel's thyroiditis. Subjects were eligible to be included only if they had non-advanced fibrotic disease in at least one organ system and otherwise met the inclusion and exclusion criteria.
- Evidence a SARS-CoV-2 (COVID-19) infection started within the 30 days prior to treatment allocation/randomization. Participants diagnosed with SARS-CoV-2 (COVID-19) infection more than 30 days prior to treatment .allocation/randomization must have symptoms resolved and be deemed fit to participate in the trial.
- Researchers consider any situations that may increase the risk to participants or interfere with the trial results (including but not limited to a history of mental illness, alcoholism, drug abuse, poor compliance, etc.).
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive lymphodepletion with fludarabine and cyclophosphamide on days -5, -4, and -3, then multiple infusions of CD19/BCMA CAR‑NK cells (KN5601) using a dose‑escalation plan. They will have repeated safety monitoring and follow‑up visits including blood tests, assessments by physicians and patients (PGA/PhGA), imaging (MRI and CT comparisons), and tests to detect CAR persistence over scheduled visits up to 48 weeks. Pregnancy testing is required at enrollment and participants must agree to use effective contraception for 6 months after the last infusion. An independent assessment committee will confirm each participant's eligibility before treatment.
How the study is structured. Single‑arm, open‑label, single‑center early‑phase study. Participants receive lymphodepletion with fludarabine and cyclophosphamide (days −5 to −3) then multiple infusions of CD19/BCMA CAR‑NK cells using a dose‑escalation plan. No placebo or comparison group. Safety and disease assessments (including imaging, clinical scores, and patient questionnaires) are collected at set times up to about 48 weeks.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- The listed sites are in China. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on IgG4-related disease
Important dates
- Study start
- Dec 30, 2025 (estimated)
- Primary completion
- Jun 26, 2028 (estimated)
- Study completion
- Dec 26, 2028 (estimated)
- Target enrollment
- 18 participants (estimated)
- Last updated on registry
- Dec 23, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Changhai Hospital
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Lei Xin 📞 086-13817318134 ✉ aip_xin@163.com
Participating sites (1)
- Changhai Hospital
Shanghai, 200433 · China
- Zhuan Liao, professor · 86-021-31161004 · liaozhuan@smmu.edu.cn
Terms used on this page · explanations by MedicalUpdates.ai
- single arm
- All participants receive the same treatment or follow the same plan. There is no comparison group within the study.
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- relapsed/refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- relapse
- A condition that improved with treatment and has since returned or worsened.
- glucocorticoids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- Echocardiography
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
- electrocardiogram
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- Estimated glomerular filtration rate
- A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
- allocation
- How participants are assigned to study groups, for example at random or by a non-random rule.
- randomization
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- exclusion criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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