Autoimmune DiseasesEarly Phase 1NCT06792799
Anti-CD19/BCMA CAR-NK Cells in Patients With B Cell Mediated Autoimmune Disease
A Early Phase 1 study testing anti-CD19/BCMA CAR NK cells (KN5601) in people with Autoimmune Diseases and Systemic Lupus Erthematosus, run by The Children's Hospital of Zhejiang University School of Medicine at 1 site in China.
Trial summary
this is an investigator-initiated trial aimed at evaluating the efficacy and safety of anti-CD19/BCMA CAR-NK Cells in Patients With B cell mediated autoimmune disease. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Autoimmune Diseases, Systemic Lupus Erthematosus, Multi-Drug Resistant Nephrotic Syndrome
- What is being tested?
- anti-CD19/BCMA CAR NK cells (KN5601)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 30 Jan 2025to 30 Jun 2029
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients or their legal guardians must acknowledge the risks and procedures involved and subsequently provide informed consent to participate in the clinical trial.
- Predicted survival time ≥ 12 weeks;
- ECOG: 0~2;
- Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% ;
- Renal function: eGFR≥30ML/min/1.73m2； (For patients with an eGFR < 30 mL/min/1.73 m² or those receiving renal replacement therapy, inclusion or exclusion in the study is determined at the discretion of the investigators. )
- Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN;
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- Lung function: No serious lung lesions, SpO2≥92%;
- Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-NK infusion;
- SLE:
- Age:≥5 years old;
- Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria；
- Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ), hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab,etc,al); or Intolerant to standard treatments; or the dosage of steroid can not be reduced to 5mg/d after 6-month of routine treatment.
- SLEDAI 2K score>6 points;
- No history of Central nervous system (CNS) disease within 60 days prior to screening;
- No history of macrophage activation syndrome (MAS) within one month prior to screening.
- MDR-SRNS
- Age ≥3 years old, gender unlimited;
- Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes （KDIGO） Guidelines and have not achieved a complete response after 12 months of treatment with two standard doses of hormone replacement drugs with different mechanisms of action or relapse of disease activity after remission (at least one of the two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus; Other hormone replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitacept or rituximab); Or if no remission has been achieved after 3 to 6 months of adequate treatment with one calcineurin inhibitor, if the researcher judges that the benefits outweigh the risks and the patient or guardian has fully informed consent, the patient can be considered for inclusion.Patients with other diseases, such as systemic lupus erythematosus, requiring long-term systemic treatment with glucocorticoids or immunosuppressants, may be considered for inclusion after the investigator determines that the benefits outweigh the risks and the patient or guardian has fully informed consent;
- Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
- IgA nephropathy
- Age: ≥ 5 years old, male or female;
- IgA nephropathy pathologically confirmed by renal biopsy;
- Angiotensin-Converting Enzyme Inhibitors (ACE) or angiotensin receptor blocker (ARB) treated for at least 3 months and meet at least one of the following requirements:
- Combination or sequential treatment with steroids and at least one immunosuppressant or biologic for ≥ 3 months; and 24-hour urine protein quantification ≥500mg or UPCR≥0.5mg/mg;
- >50% decline in eGFR within 3 months;
- Patients who are unable to tolerate conventional treatment and for whom the investigator determines the benefits outweigh the risks and who have obtained fully informed consent from the patient or guardian may be considered for inclusion;
- Exclude subjects with other secondary causes; exclude patients with uncontrolled blood pressure.
Who cannot join
- Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or subjects with a history of severe allergic reactions
- Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
- Subjects with grade III or IV heart failure (NYHA classification)
- Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
- Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
- Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
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- Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening;
- Patients had seizure, or other active central nervous system disease;
- Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases;
- Secondary or congenital immunodeficiency.
- History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of KN5601, except for lupus (determined by the investigator)
- Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening;
- Received live vaccine within 4 weeks before screening;
- Subjects who have received B cell-targeted drug therapy within 1 month before enrollment
- Tested positive in Blood pregnancy test；
- Patients who participated in other clinical study within 3 months prior to enrollment;
- Any abnormal laboratory test results judged by the investigator to be clinically significant and prevent the subject from participating in the study. Laboratory test values that are out of range and not of clinical significance will not be considered as exclusion criteria
- Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000
Hangzhou, Zhejiang, 310052
Jianhua Mao, PhD, 13516819071, maojh88@zju.edu.cn
Jianhua Mao, PhD
About this study
Official title: An Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor NK Cells in the Treatment of B Cell-related Autoimmune Diseases in Children
this is an investigator-initiated trial aimed at evaluating the efficacy and safety of anti-CD19/BCMA CAR-NK Cells in Patients With B cell mediated autoimmune disease.
Read the detailed description
Autoimmune diseases are conditions in which the immune system fails to accurately recognize normal tissues or cells, leading to the attack of organs, tissues, or cells.
Systemic lupus erythematosus (SLE) is a severe autoimmune disorder that can cause widespread damage to multiple organs and systems, ultimately resulting in disability and even death. Pediatric patients with SLE are particularly susceptible to organ damage, especially renal impairment, and typically experience a more severe and protracted disease course compared to adults. Despite advances in therapy, many patients continue to suffer from SLE. In China, only 0.76% to 25% of patients achieve drug-free or clinical remission, highlighting the urgent need for novel therapeutic approaches.
For patients with multi-drug resistant nephrotic syndrome (MDR-SRNS), who are at high risk of progressing to kidney failure, there remains no effective treatment. Therefore, there is a pressing need for new therapeutic strategies.
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although immunosuppressants have been used in some patients, IgAN remains a leading cause of kidney failure in young adults, with approximately 40% of patients progressing to end-stage kidney disease (ESKD) within 20-30 years.
Since 2019, CAR T-cell therapy has shown success in treating various autoimmune diseases, including SLE, systemic sclerosis, and idiopathic inflammatory dermatomyositis. However, the widespread application of autologous CAR T-cells is limited by several factors, including their high cost and the frequent occurrence of adverse effects. Autologous CAR T-cells are personalized products, which make them expensive and less accessible. Furthermore, the risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain significant concerns.
Chimeric antigen receptor natural killer (CAR-NK) cell therapy offers a promising alternative. This adoptive cell therapy involves the genetic modification of NK cells to recognize and eliminate target cells expressing disease-related antigens. CAR-NK cells have several advantages over CAR T-cells, including a lower risk of graft-versus-host disease (GVHD) and minimal occurrence of CRS or ICANS. Additionally, CAR-NK therapy is more cost-effective, which could greatly enhance its accessibility.
Given these advantages, CAR-NK cell therapy holds potential for revolutionizing the treatment of refractory SLE and MDR-SRNS, IgAN, offering new hope for patients with these challenging conditions.
- Conditions
- Autoimmune Diseases, Systemic Lupus Erthematosus, Multi-Drug Resistant Nephrotic Syndrome, IgAN - IgA Nephropathy
- Being tested
- anti-CD19/BCMA CAR NK cells (KN5601)
- Keywords
- car-nk, Multi-Drug Resistant Nephrotic Syndrome, Systemic Lupus Erthematosus, IgAN - IgA Nephropathy
- Medical subject headings
- Autoimmune Diseases, Nephrotic Syndrome, Glomerulonephritis, IGA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD19/BCMA CAR NK cells (KN5601)Biological
Patients will receive Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of anti-CD19/BCMA CAR NK cells (KN5601) will infused in each group using dose-escalation strategy.
| Study group | Role | What they receive |
|---|---|---|
| anti-CD19/BCMA CAR NK cells | Experimental | The study adopted a dose-escalation and expansion study design. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19/BCMA CAR NK cells infusion. Receives: Biological: anti-CD19/BCMA CAR NK cells (KN5601) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of CAR-NK cell therapy in patients with B cell mediated autoimmune disease
Incidence of Dose Limiting Toxicity (DLTs), Incidence and severity of Adverse Events (AEs) and Serious Adverse Event（SAEs）.
Measured: 1 months
The efficiency of CAR-NK cell therapy in patients with B cell mediated autoimmune disease
SLE: The rate of patients achieving SRI-4 response, LLDAS, or DORIS remission MDR-SRNS:Complete response and partial response rate. IgAN:partial or complete response.
Measured: 3 months
Secondary outcomes (1)
Effectiveness of other visit points
The responsive rate and the rate of complete /partial remission
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2025
- Study start30 Jan 2025
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by The Children's Hospital of Zhejiang University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mao Jianhua, The Children's Hospital of Zhejiang University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06792799
- Sponsor's protocol ID
- 2025-SC-0002-P-01
- Status last verified
- Sep 2025
- First submitted
- 20 Jan 2025
- Last updated
- 1 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor NK Cells in the Treatment of B Cell-related Autoimmune Diseases in Children
- ClinicalTrials.gov ID
- NCT06792799
- Acronym / sponsor ID
- 2025-SC-0002-P-01
- Conditions
- Autoimmune Diseases, Systemic Lupus Erthematosus, Multi-Drug Resistant Nephrotic Syndrome, IgAN - IgA Nephropathy
- Keywords
- car-nk, Multi-Drug Resistant Nephrotic Syndrome, Systemic Lupus Erthematosus, IgAN - IgA Nephropathy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- The Children's Hospital of Zhejiang University School of MedicineUniversity, hospital or other
- Study start
- 30 Jan 2025 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 27 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
this is an investigator-initiated trial aimed at evaluating the efficacy and safety of anti-CD19/BCMA CAR-NK Cells in Patients With B cell mediated autoimmune disease.
Detailed description
Autoimmune diseases are conditions in which the immune system fails to accurately recognize normal tissues or cells, leading to the attack of organs, tissues, or cells.
Systemic lupus erythematosus (SLE) is a severe autoimmune disorder that can cause widespread damage to multiple organs and systems, ultimately resulting in disability and even death. Pediatric patients with SLE are particularly susceptible to organ damage, especially renal impairment, and typically experience a more severe and protracted disease course compared to adults. Despite advances in therapy, many patients continue to suffer from SLE. In China, only 0.76% to 25% of patients achieve drug-free or clinical remission, highlighting the urgent need for novel therapeutic approaches.
For patients with multi-drug resistant nephrotic syndrome (MDR-SRNS), who are at high risk of progressing to kidney failure, there remains no effective treatment. Therefore, there is a pressing need for new therapeutic strategies.
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although immunosuppressants have been used in some patients, IgAN remains a leading cause of kidney failure in young adults, with approximately 40% of patients progressing to end-stage kidney disease (ESKD) within 20-30 years.
Since 2019, CAR T-cell therapy has shown success in treating various autoimmune diseases, including SLE, systemic sclerosis, and idiopathic inflammatory dermatomyositis. However, the widespread application of autologous CAR T-cells is limited by several factors, including their high cost and the frequent occurrence of adverse effects. Autologous CAR T-cells are personalized products, which make them expensive and less accessible. Furthermore, the risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain significant concerns.
Chimeric antigen receptor natural killer (CAR-NK) cell therapy offers a promising alternative. This adoptive cell therapy involves the genetic modification of NK cells to recognize and eliminate target cells expressing disease-related antigens. CAR-NK cells have several advantages over CAR T-cells, including a lower risk of graft-versus-host disease (GVHD) and minimal occurrence of CRS or ICANS. Additionally, CAR-NK therapy is more cost-effective, which could greatly enhance its accessibility.
Given these advantages, CAR-NK cell therapy holds potential for revolutionizing the treatment of refractory SLE and MDR-SRNS, IgAN, offering new hope for patients with these challenging conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-CD19/BCMA CAR NK cells | Experimental | Biological: anti-CD19/BCMA CAR NK cells (KN5601)The study adopted a dose-escalation and expansion study design. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19/BCMA CAR NK cells infusion. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (27 listed)
- Patients or their legal guardians must acknowledge the risks and procedures involved and subsequently provide informed consent to participate in the clinical trial.
- Predicted survival time ≥ 12 weeks;
- ECOG: 0~2;
- Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% ;
- Renal function: eGFR≥30ML/min/1.73m2； (For patients with an eGFR < 30 mL/min/1.73 m² or those receiving renal replacement therapy, inclusion or exclusion in the study is determined at the discretion of the investigators. )
Key exclusion criteria (18 listed)
- Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or subjects with a history of severe allergic reactions
- Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
- Subjects with grade III or IV heart failure (NYHA classification)
- Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
- Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-CD19/BCMA CAR NK cells (KN5601)Patients will receive Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of anti-CD19/BCMA CAR NK cells (KN5601) will infused in each group using dose-escalation strategy. | Biological | anti-CD19/BCMA CAR NK cells |
Primary outcome
The safety of CAR-NK cell therapy in patients with B cell mediated autoimmune disease
Time frame: 1 months
Incidence of Dose Limiting Toxicity (DLTs), Incidence and severity of Adverse Events (AEs) and Serious Adverse Event（SAEs）.
The efficiency of CAR-NK cell therapy in patients with B cell mediated autoimmune disease
Time frame: 3 months
SLE: The rate of patients achieving SRI-4 response, LLDAS, or DORIS remission MDR-SRNS:Complete response and partial response rate. IgAN:partial or complete response.
1 secondary outcome
Effectiveness of other visit points
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing anti-CD19/BCMA CAR NK cells (KN5601) in people with Autoimmune Diseases and Systemic Lupus Erthematosus, run by The Children's Hospital of Zhejiang University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jianhua Mao, PhD (13516819071, maojh88@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety of CAR-NK cell therapy in patients with B cell mediated autoimmune disease (time frame: 1 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.