RD06-05 Universal CD19/BCMA CAR-T for Refractory Pediatric Autoimmune Diseases

A Clinical Study of the Safety, Efficacy, and Pharmacokinetics of Universal CD19/BCMA-Targeted CAR-T Cell Injection for the Treatment of Autoimmune Diseases in Children and Adolescents

This is a single-arm, open-label, phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of RD06-05, a universal CD19/BCMA dual-targeting chimeric antigen receptor T-cell (CAR-T), in pediatric and adolescent patients with refractory autoimmune diseases, including systemic lupus erythematosus/lupus nephritis (SLE/LN), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), multidrug-resistant nephrotic syndrome (MDR-NS), and refractory IgA nephropathy (IgAN).

Approximately 30 eligible patients will be enrolled and receive a single intravenous infusion of RD06-05 at an initial dose of 6×10⁶ CAR+ T cells/kg, with a potential dose escalation to 10×10⁶ CAR+ T cells/kg following review by a Safety Review Committee (SRC).

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Diseases; IgAN - IgA Nephropathy; SLE - Systemic Lupus Erythematosus; Multi-Drug Resistant Nephrotic Syndrome; IIM- Idiopathic Inflammatory Myopathies; SSc-Systemic Sclerosis
• Intervention / Treatment: Drug: RD06-05 CART Cell Infusion

Detailed Description

Study Duration:

Approximately 4 years (2026-2030), with individual participant participation lasting up to 24 months post-infusion.

Follow-up:

Patients are followed for safety, efficacy, PK/PD, and quality of life assessments at predefined time points through 24 months post-infusion.

Key Endpoints:

Primary: Incidence of TEAEs, SAEs, and AESIs (including cytokine release syndrome, ICANS, GvHD, infections, and secondary malignancies).

Secondary: Disease-specific response rates (e.g., LLDAS/DORIS for SLE/LN, mRSS for SSc, MMT-8 for IIM, UPCR for IgAN, remission for MDR-NS), changes in eGFR, autoantibody levels, quality of life (PedsQL 4.0), CAR-T expansion (Cmax, AUC0-28), persistence, and anti-drug antibody incidence.

Exploratory: B-cell aplasia duration and B-cell subset reconstitution.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jianhua Mao; Phone Number: +86 13516819071; Email: maojh88@zju.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Nanjing Children's Hospital
      • Contact: Haiguo Yu; Phone Number: 025-83117500; Email: njetyy@njch.com.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Children's Hospital, Zhejiang University School of Medicine
      • Contact: Jianhua Mao; Phone Number: +86 13516819071; Email: maojh88@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary participation with signed informed consent from patient or legal guardian.
2. Age >=5 to <20 years, male or female.
3. Important organ function meeting the following requirements (excluding abnormalities related to autoimmune disease activity): a) Bone marrow: ANC >=1.0x10^9/L, hemoglobin >=60 g/L, platelets >=30x10^9/L; b) Liver: ALT <=3xULN (except IIM-related elevation), AST <=3xULN, total bilirubin <=2xULN (<=3xULN for Gilbert syndrome); c) Kidney: eGFR >=30 mL/min/1.73m^2 (lower eGFR or on renal replacement may be allowed if benefit > risk by investigator judgment); d) Cardiac: LVEF >=55% by echocardiogram; e) Pulmonary: No severe lung disease, SpO2 >=92%.
4. Negative serum or urine pregnancy test for females of childbearing potential at screening.

5. Females of childbearing potential must use highly effective contraception from at least 28 days before lymphodepletion through 12 months post-infusion. Males must use effective barrier contraception and not donate sperm from start of lymphodepletion through 12 months post-infusion.

   Disease-Specific Inclusion Criteria for SLE/LN:

6. Diagnosis of SLE by 2019 EULAR/ACR or 2012 SLICC criteria.
7. If renal involvement: kidney biopsy within 2 years showing active nephritis (class III, IV, V, or combination). Renal involvement defined as proteinuria >0.15g/24h, or hematuria, or eGFR <90.Inadequate response to standard therapy: high-dose glucocorticoid (>=1 mg/kg/d prednisone equivalent) + hydroxychloroquine + at least 2 DMARDs for 3 months, or intolerance, or unable to taper steroid to <=5 mg/day at 6 months.
8. Positive ANA, anti-dsDNA, or anti-Smith antibody.
9. SLEDAI-2K >=8 and clinical SLEDAI-2K >=4 (renal proteinuria >0.5g/24h or UPCR >500 mg/g or active urinary sediment may waive the clinical SLEDAI-2K requirement).

10. Physician Global Assessment (PGA) >=1.0 (0-3 VAS).

    Disease-Specific Inclusion Criteria for SSc:

11. Diagnosis of SSc by 2013 ACR/EULAR criteria.
12. Diffuse cutaneous SSc.
13. Evidence of active disease (e.g., new SSc within 2 years, new skin involvement or worsening mRSS within 6 months, tendon friction rubs, lung function decline, ILD progression).
14. FVC >=50% and DLCO >=45% predicted.

15. Failed or relapsed on conventional therapy (glucocorticoid >0.5 mg/kg/d prednisone equivalent + at least two immunomodulators for >6 months).

    Disease-Specific Inclusion Criteria for IIM:

16. Diagnosis of IIM (dermatomyositis, antisynthetase syndrome, IMNM) by 2017 ACR/EULAR criteria (probability >=55%).
17. Active disease: at least 2 of 6 core set abnormalities (MMT-8<142, PhGA >=2 cm, PtGA >=2 cm, extra-muscular MDAAT >=2 cm, PedsQL >=60, CK >=1.5xULN).
18. Positive myositis-specific autoantibody.

19. Failed or relapsed on conventional therapy (glucocorticoid >1 mg/kg/d prednisone equivalent + at least 2 immunomodulators for >=6 months).

    Disease-Specific Inclusion Criteria for IgAN:

20. Biopsy-confirmed IgA nephropathy.
21. On ACEi/ARB for >=3 months, and at least one of: a) proteinuria >=500 mg/24h or UPCR >=0.5 mg/mg after >=3 months of steroid + at least one immunosuppressant/biologic; b) eGFR decline >50% within 3 months; c) 22.intolerance to conventional therapy with benefit > risk.

Disease-Specific Inclusion Criteria for MDR-NS:

23.Meets 2025 KDIGO definition of steroid-resistant nephrotic syndrome. 24.At least one of: a) failed to achieve remission after 12 months of two different mechanism steroid-sparing agents (at least one calcineurin inhibitor); b) no remission after 3-6 months of one CNI with benefit > risk; c) intolerance to conventional therapy; d) coexisting systemic disease requiring long-term immunosuppression.

25.Prior kidney biopsy showing minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS).

Exclusion Criteria:

1. Co-existing autoimmune disease that may interfere with disease activity attribution or add safety risk (unless stable >=3 months and approved).
2. Prior B-cell/ASC depletion therapy: a) Anti-CD20 or T-cell engager within 3 months (allowed if >3-6 months and CD19+ B-cells > LLN); b) Prior CD19 and BCMA dual-targeted therapy, or CD19 or BCMA targeted therapy within 6 months (allowed if >6 months and B-cells > LLN); c) Other B-cell/ASC targeted therapies require approval.
3. Rapidly progressive glomerulonephritis (RPGN): >=50% crescents on biopsy, or doubling of serum creatinine within 2 months, or investigator judgment.
4. Cardiac disease: NYHA class III/IV heart failure, MI, angioplasty/stent, unstable angina, or other severe cardiac disease within 12 months.
5. Severe CNS disease (traumatic brain injury, impaired consciousness, epilepsy, cerebrovascular ischemia/hemorrhage) that may affect compliance or assessment.
6. Malignancy history except cured non-melanoma skin cancer or carcinoma in situ, unless disease-free for >=3 years.
7. Primary immunodeficiency.
8. Uncontrolled infection (simple UTI or upper respiratory infection allowed).
9. Known history of HIV, hepatitis C, or syphilis infection.
10. Active or latent hepatitis B infection.
11. Positive EBV or CMV DNA or IgM at screening.
12. History of recurrent tuberculosis.
13. Prior CAR-T or other transgenic immune cell therapy.
14. Live attenuated vaccine within 4 weeks before enrollment.
15. Allergy to any component of the cell therapy product.
16. Hypersensitivity to tacrolimus or prior grade >=3 tacrolimus-related toxicity requiring hospitalization (exceptions may be approved).
17. Participation in another clinical trial within 30 days before screening.
18. Pregnancy, breastfeeding, or unwillingness to use effective contraception.

19. Any other condition judged by investigator as unsuitable for study.

    Disease-Specific Exclusion Criteria for SLE:

20. Active/unstable neuropsychiatric lupus (seizures, psychosis, organic brain syndrome, CVA, encephalitis, CNS vasculitis) within 90 days requiring intervention.
21. Prior treatments: belimumab/telitacicept within 4 weeks; ianalumab within 8 weeks unless B-cells > LLN; >1 systemic NSAID within 14 days; inability to wash out NSAID before disease activity assessment; intra-articular/IM glucocorticoid within 6 weeks; immunosuppressant doses above specified limits; initiation or dose change of hydroxychloroquine within 8 weeks; ACEi/ARB/SGLT2 inhibitor dose change within 4 weeks.

22. Disease flare requiring increased corticosteroids (>20 mg/day prednisone equivalent) or new immunosuppression during screening.

    Disease-Specific Exclusion Criteria for IIM:

23. Severe rhabdomyolysis or CK >=20xULN.

24. FVC <=60% predicted, or DLCO <=70% predicted, or worsening lung function compared to prior 3-12 months.

    Disease-Specific Exclusion Criteria for SSc:

25. Anti-centromere antibody positive without ATA or anti-RNAP3.
26. Clinically significant respiratory disease other than ILD (severe COPD, severe asthma, recent severe respiratory infection, smoking).
27. FVC <50% or DLCO <40% predicted.
28. On lung transplant list or expected within 12 months.
29. History of scleroderma renal crisis within 6 months.
30. SSc-like disorders (morphea, eosinophilic fasciitis, etc.).
31. Antifibrotic drugs within 4 weeks (colchicine, D-penicillamine, pirfenidone, tyrosine kinase inhibitors).

32. Prior chlorambucil, bone marrow transplant, or total lymphoid irradiation.

    Disease-Specific Exclusion Criteria for IgAN:

33. Secondary IgAN (cirrhosis, celiac disease, HIV, malignancy).
34. Other cause of chronic kidney disease (diabetic nephropathy, other primary glomerulopathy) that may interfere.
35. Uncontrolled blood pressure.

36. Prior treatments: hydroxychloroquine dose change within 8 weeks; biologics (infliximab, eculizumab, canakinumab) within 4 weeks; prednisone >30 mg/day or unstable dose; endothelin receptor antagonist within 4 weeks before lymphodepletion.

    Disease-Specific Exclusion Criteria for MDR-NS:

37. Secondary nephrotic syndrome/proteinuria (infection-related, drug-related, systemic disease) that may interfere.
38. On maintenance dialysis, need for immediate renal replacement, or expected dialysis/transplant within 12 months.
39. Prior treatments: ACEi/ARB dose change within 4 weeks; glucocorticoid dose adjustment within 2 weeks or need for >10 mg/day prednisone equivalent; 40.disease flare requiring increased steroids (>10 mg/day) or new immunosuppression during screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RD06-05 Universal CAR-T Therapy; Single-arm, open-label: participants receive a single intravenous infusion of RD06-05 (universal CD19/BCMA dual-targeting CAR-T cells) following a lymphodepleting regimen of fludarabine and cyclophosphamide.	Drug: RD06-05 CART Cell Infusion; CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)	Incidence of TEAEs, SAEs, and AESIs following RD06-05 infusion. AESIs include cytokine release syndrome (CRS) of grade ≥3, immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade, graft-versus-host disease (GvHD) of any grade, infections of grade ≥3, secondary malignancies of any grade, and cardiac disorders of any grade.	From signing of informed consent through 90 days post-infusion (for related AEs, up to 24 months post-infusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of SLE/LN Patients Achieving LLDAS and DORIS Remission	Proportion of patients with systemic lupus erythematosus/lupus nephritis (SLE/LN) who achieve Lupus Low Disease Activity State (LLDAS) and DORIS remission, including drug-free remission.	2 years
Renal Response in SLE/LN Patients with Renal Involvement	Proportion of SLE/LN patients with renal involvement achieving complete renal response (CRR) and partial response, and change from baseline in UPCR (urine protein-to-creatinine ratio) and eGFR.	2 years
Change in SLE Disease Activity Scores	Change from baseline in SLEDAI-2K score(range from 0 to105, higher scores mean a worse outcome).	2 years
Change in SLE Disease Activity Scores	Change from baseline in Physician Global Assessment (PGA : range from 0 to 3, higher scores mean a worse outcome).	2years
Change in SLE Disease Activity Scores	Change from baseline in British Isles Lupus Assessment Group (BILAG) score ( range from A to E, higher grade means a better outcome)..	2years
Change in Autoantibody Levels in SLE/LN	Change from baseline in anti-dsDNA antibody levels.	2 years
Change in Complement Levels in SLE/LN	Change from baseline in c omplement(C3/C4) levels.	2 years
Major Clinical Response in IIM Patients	Proportion of patients with idiopathic inflammatory myopathy (IIM) achieving major clinical response according to 2016 ACR/EULAR myositis response criteria	2 years
Change in Skin and Lung Function in SSc Patients	Change from baseline in modified Rodnan skin score (mRSS) , for patients with interstitial lung disease, change from baseline in FVC and DLCO.	2 years
Change in Skin and Lung Function in SSc Patients	Change from baseline in EUSTAR activity index; for patients with interstitial lung disease, change from baseline in FVC and DLCO.	2 years
Remission and Renal Outcomes in MDR-NS Patients	Proportion of patients with complete remission (CR), partial remission (PR), and overall response rate (CR+PR); change from baseline in serum albumin and eGFR; time to first composite renal outcome event (sustained eGFR decline ≥30%, eGFR <15 mL/min/1.73m², maintenance dialysis/kidney transplant, or renal death).	2 years
Change in Quality of Life (PedsQL 4.0)	Change from baseline in Pediatric Quality of Life Inventory (PedsQL 4.0) score ( range from 0 to 100, higher scores mean a better outcome)..	2 years
Pharmacokinetics - CAR-T Expansion	Peak expansion (Cmax) of RD06-05 CAR-T cells in peripheral blood.	2 years
Immunogenicity - Anti-Drug Antibodies (ADA)	Incidence of anti-drug antibodies (ADA) specific to RD06-05.	2 years
Proteinuria in IgAN Patients	Proportion of patients achieving UPCR < 1 g/g.	2 years
Proteinuria in IgAN Patients	Change from baseline in UPCR	2 years
Renal Function in IgAN Patients	Change from baseline in eGFR.	2 years.
Renal Function in IgAN Patients	Change from baseline in eGFR slope.	2 years
Renal Function in IgAN Patients	Proportion with eGFR decline ≥30%	2 years
Renal Function in IgAN Patients	Time to first composite kidney failure endpoint (sustained eGFR decline ≥30%, eGFR <15 mL/min/1.73m², maintenance dialysis, kidney transplant, or renal death).	2 years
Duration of peripheral blood B-cell aplasia	Duration of peripheral blood B-cell aplasia following RD06-05 infusion.	2 years
Pharmacokinetics - CAR-T Expansion	Area under the curve from day 0 to day 28 (AUC0-28) of RD06-05 CAR-T cells in peripheral blood.	2 years
Pharmacokinetics - CAR-T Persistence	Persistence of RD06-05 CAR-T cells in peripheral blood.	2 years
Immunogenicity - Anti-Drug Antibodies (ADA)	Titer of anti-drug antibodies (ADA) specific to RD06-05.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of B-Cell Aplasia	Incidence of peripheral blood B-cell aplasia following RD06-05 infusion.	2 years
Changes in B-Cell Subsets	Changes in peripheral blood B-cell subsets.	2 years

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine
• Investigators: Principal Investigator: Jianhua Mao, The Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Nephrosis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Autoimmune Diseases; Glomerulonephritis, IGA; Nephrotic Syndrome
• Other Study ID Numbers: BHCT-RD06-05-PAID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No