Safety and Efficacy of PRG-1801 for Refractory Lupus Nephritis and IgG4-Related Disease

NCT ID: NCT06497387

Last Updated: 2024-07-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2028-07-31

Brief Summary

A Clinical Study on the Safety and Effectiveness of BCMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Lupus Nephritis and IgG4-Related Disease.

Conditions

Lupus Nephritis; IgG4-related Disease

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BCMA-targeting CAR T cells therapy

The study was divided into two phases: dose exploration phase and dose extension phase. Three dose levels (35×10^6 CAR-T, 100×10^6 CAR-T, 300×10^6 CAR-T) were planned for the dose-exploration phase, and 3 to 6 LN or IgG4-RD subjects were included in each dose group. When 1 out of 3 subjects in a dose group showed DLT, 3 subjects were re-enrolled at that dose level. If DLT occurs in ≥2 of 6 subjects, dose reduction or study termination should be considered.

The safe and effective fixed dose of PRG-1801 was determined through the dose-exploration phase, and after evaluation by the investigators, the dose-expansion phase was conducted, in which an additional 3-6 subjects were included in the safe and effective fixed dose for each of the two indications (Lupus Nephritis and IgG4-Related Disease) to further determine the safety and efficacy of this dose for each indications.

Group Type: EXPERIMENTAL

PRG-1801

Intervention Type: BIOLOGICAL

PRG-1801 (BCMA-targeting CAR-T Cells)

Interventions

PRG-1801

PRG-1801 (BCMA-targeting CAR-T Cells)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

A. Age ≥ 18 years old; B. If the kidneys are involved, estimate the glomerular filtration rate (eGFR) to be ≥ 15 mL/minute/1.73 m2;

C. The following test values within 3 days before the collection of mononuclear cells meet the following standards:

1. Absolute lymphocyte count: ≥ 0.5 × 10 ^ 9/L [The use of granulocyte colony-stimulating factor (G CSF) is allowed, but subjects are not allowed to receive this supportive treatment within 7 days before the screening period laboratory examination];

2. Absolute neutrophil count: ≥ 1.0 × 10 ^ 9/L [The use of granulocyte colony-stimulating factor (G-CSF) is allowed, but subjects are not allowed to receive this supportive treatment within 7 days before the screening period laboratory examination];

3. Platelets: Subject platelet count ≥ 50 × 10 ^ 9/L (subjects are not allowed to receive blood transfusion support within 7 days before the screening period laboratory examination);

4. Hemoglobin: ≥ 8.0 g/dL (allowing the use of recombinant human erythropoietin) [subjects have not received red blood cell (RBC) infusion within 7 days prior to the screening period laboratory examination];

5. Creatinine clearance rate: (CrCl) or glomerular filtration rate (GFR) (Cockcroft Gault formula) ≥ 30 mL/min;

6. Total bilirubin (serum): Total bilirubin (serum) ≤ 1.5 × ULN; Blood bilirubin>1.5 × Gilbert subjects from ULN can be enrolled with the consent of the sponsor AST and ALT: ≤ 3.0 × ULN;

7. Plasma prothrombin time (PT), international standardized ratio (INR), partial prothrombin time (APTT): PT ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN, INR ≤ 1.5 × ULN Willing to sign an informed consent form.

8. Fertile men and women of childbearing age must agree to use effective contraception from the time they sign an informed consent and up to 1 year after the study drug is used. Blood pregnancy tests for women of reproductive age at the time of screening and before cell infusion must be negative.

9. The patients or their guardians agree to participate in the clinical study and sign the informed consent, indicating that they understand the purpose and procedure of the clinical study and are willing to participate in the study.

• for refractory LN

A. According to the 2019 American Society of Rheumatology (ACR) criteria, diagnosed with systemic lupus erythematosus, within 6 months prior to infusion, confirmed by renal tissue biopsy according to the 2003 International Society of Nephrology (ISN)/Society of Nephropathology (RPS) criteria as active, proliferative lupus nephritis (LN), type III or IV, or type III/IV combined with type V, or type V. And have received standard treatment that is ineffective or relapses after disease remission.

B. Positive anti-nuclear antibodies (ANA) and/or anti-dsDNA antibodies during the screening period.

C. The SLE Disease Activity Index (SLEDAI-2000) score during the screening period is ≥ 8. SLEDAI-2000 clinical score ≥ 6 points, but low complement and/or anti ds-DNA positivity can be selected.

-for refractory IgG4-RD

A. According to the 2019 ACR/EULAR criteria, diagnosed with IgG4-RD; B. The clinical manifestations were recurrent or refractory IgG4-RD; C. IgG4-RD response index (RI) ≥2, the disease is in the active stage; D. meet the clinical phenotype of Mikulitz/systemic

Exclusion Criteria

Subjects who meet any of the following criteria should be excluded from this study:

1. Pregnant or lactating women;

2. A history of malignant tumors within 5 years (① subjects with cervical carcinoma in situ who have been completely removed and have not experienced recurrence or metastasis for at least 3 years may participate in this study. ② subjects with basal cell or squamous cell carcinoma who have been completely removed and have not experienced recurrence for at least 3 years may participate in this study);（①Carcinoma in situ of the cervix that has undergone curative treatment for more than 12 months prior to screening, ②Basal cell or squamous cell carcinoma of the skin that has been treated therapeutically, ③ Prostate cancer that has been treated with radical prostatectomy or curative radiation therapy for more than 3 years prior to screening has no known recurrence and is not currently receiving treatment；④have had surgery for thyroid cancer, and have not evidence of active disease）;

3. Received any B-cell depletion biologic therapy (for example, rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab, etc) in the 6 months prior to CAR-T reinfusion, unless B-cell recovery was demonstrated;

4. Received immunosuppressant therapy within 3 days prior to CAR-T reinfusion, or systemic corticosteroid therapy (>10 mg/ day of prednisone or equivalent doses of other corticosteroids) within 3 days prior to CAR-T reinfusion;

5. Received live vaccine or live therapeutic STDS within 2 weeks prior to screening;

6. The presence of chronic and active hepatitis B (except for HBV DNA testing below 500IU/ml), hepatitis C (HCV), human immunodeficiency virus (HIV) infection, or syphilis infection;

7. With an active infection that requires intravenous antibiotics or hospitalization;

8. Obvious evidence of cardiovascular disease as follows: a N-terminal B-type natriuretic peptide (NT proBNP)>8500ng/L; b. The New York Heart Association (NYHA) classifies heart failure as Grade IV; c. Patients who received hospitalization for unstable angina or myocardial infarction within 6 months prior to the first administration, or patients who received percutaneous cardiac intervention and received the most recent stent placement within 6 months or coronary artery bypass grafting within 6 months;

9. People who have a known allergy, hypersensitivity, intolerance, or contraindication to any component of PRG-1801 or the drugs that may be used in the study, including fludarabine, cyclophosphamide, tolumab, or albumin, or who have had a prior severe allergic reaction;

10. Patients with other conditions determined by the investigator to be unsuitable for lymphocyte clearance or cell infusion, or who are otherwise unsuitable for study participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Pregene Biopharma Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lingli Dong

Professor of the department of rheumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lingli Dong, MD

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

Tongji Hospital

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lingli Dong, MD

Role: CONTACT

tjhdongll@163.com

02783665519

Ziwei Hu, MD

Role: CONTACT

836048368@qq.com

02783665518

Facility Contacts

Lingli Dong, MD

Role: primary

tjhdongll@163.com

02783665519

Ziwei Hu

Role: backup

836048368@qq.com

02783665518

Other Identifiers

S113

Identifier Type: -

Identifier Source: org_study_id