Safety and Efficacy of PRG-2311 for Refractory Lupus Nephritis and IgG4-Related Disease

NCT06497361 | Recruiting Early Phase 1

• 1 other identifier: S114
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A Clinical Study on the Safety and Effectiveness of CD19/BCMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Lupus Nephritis and IgG4-Related Disease.

Conditions

Lupus Nephritis; IgG4-related Disease

Outcome Measures

Primary Outcomes (2)

• Safe dose of PRG-2311 infusion

  To evaluate the safe dose of PRG-2311 infusion, 3 dosage group were designed in this trial, they are 35×10\^6 CAR-T, 100×10\^6 CAR-T, and 300×10\^6 CAR-T

  Up to 24 months after PRG-2311 infusion

• Occurrence of AE after PRG-2311 infusion

  To evaluate the occurrence of AE after PRG-2311 infusion based on CTCAE v5.0

  Up to 24 months after PRG-2311 infusion

Secondary Outcomes (23)

• LN: Changes of SLE disease activity Index (SLEDAI-2000) score

  Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion

• LN: Changes of FACIT score

  Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion

• LN: Changes of PGA score

  Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion

• LN: Changes of UPCR

  Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion

• LN: Changes of eGFR

  Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion

Study Arms (1)

CAR T cells therapy

EXPERIMENTAL

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-2311 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.

Biological: PRG-2311

Interventions

PRG-2311 BIOLOGICAL

PRG-2311 (CD19/BCMA-targeting CAR-T Cells)

CAR T cells therapy

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old;
• If the kidneys are involved, estimate the glomerular filtration rate (eGFR) to be ≥ 15 mL/minute/1.73 m2;
• The following test values within 3 days before the collection of mononuclear cells meet the following standards:
• Absolute lymphocyte count: ≥ 0.5 × 10 \^ 9/L \[The use of granulocyte colony-stimulating factor (G CSF) is allowed, but subjects are not allowed to receive this supportive treatment within 7 days before the screening period laboratory examination\];
• Absolute neutrophil count: ≥ 1.0 × 10 \^ 9/L \[The use of granulocyte colony-stimulating factor (G-CSF) is allowed, but subjects are not allowed to receive this supportive treatment within 7 days before the screening period laboratory examination\];
• 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);
• Hemoglobin: ≥ 8.0 g/dL (allowing the use of recombinant human erythropoietin) \[subjects have not received red blood cell (RBC) infusion within 7 days prior to the screening period laboratory examination\];
• Creatinine clearance rate: (CrCl) or glomerular filtration rate (GFR) (Cockcroft Gault formula) ≥ 30 mL/min;
• 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;
• 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.
• 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.
• 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
• 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.
• Positive anti-nuclear antibodies (ANA) and/or anti-dsDNA antibodies during the screening period.

You may not qualify if:

• Subjects who meet any of the following criteria should be excluded from this study:
• Pregnant or lactating women;
• A history of malignant tumors within 5 years （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）;
• 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;
• 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;
• Received live vaccine or live therapeutic STDS within 2 weeks prior to screening;
• 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;
• With an active infection that requires intravenous antibiotics or hospitalization;
• 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;
• People who have a known allergy, hypersensitivity, intolerance, or contraindication to any component of PRG-2311 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;
• 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.

Sponsors & Collaborators

• Tongji Hospital: lead
• Shenzhen Pregene Biopharma Co., Ltd.: collaborator

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Conditions

Lupus Nephritis; Immunoglobulin G4-Related Disease

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Lingli Dong

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lingli Dong

CONTACT

02783665519; tjhdongll@163.com

Ziwei Hu

CONTACT

02783665518; 836048368@qq.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of the department of rheumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: July 11, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)