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 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.

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.