IM19 CAR-T Cell Therapy for IgA Nephropathy Patients and Membranous Nephropathy Patients

NCT06690359 | Not Yet Recruiting Early Phase 1

• 1 other identifier: ZMA02
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

IM19 CAR-T cell therapy for IgA nephropathy patients with urinary protein and renal dysfunction, as well as patients with intermediate to high-risk primary membranous nephropathy

Conditions

IgA Nephropathy; Membranous Nephropathy

Outcome Measures

Primary Outcomes (4)

• IgA nephropathy-Main safety endpoint（Adverse event incidence rate）

  The incidence of adverse events related to IM19 CAR-T cell reinfusion within 28 days after IM19 CAR-T cell reinfusion, as well as clinically significant laboratory test results.

  IM19 CAR-T cell reinfusion within 28 days

• IgA primary efficacy endpoint（Urinary protein ratio）

  Changes in urinary protein levels (1 day, 14 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months after initial administration) relative to baseline values and the rate of reaching the threshold

  6 months after the first administration

• PMN primary safety endpoint（Adverse event incidence rate）

  The incidence of adverse events related to IM19 CAR-T cell reinfusion within 28 days after IM19 CAR-T cell reinfusion, as well as clinically significant laboratory test results.

  IM19 CAR-T cell reinfusion within 28 days

• PMN primary efficacy endpoint（Relief rate）

  Evaluate the overall response rate (CR+PR), complete response rate, and partial response rate of the subjects 6 months after the first infusion. Complete remission criteria: Urinary protein ≤ 0.3g and serum albumin\>3.5g/dl. Partial relief criteria: Urinary protein reduction\>50% compared to baseline and final 0.3g\<urinary protein ≤ 3.5g.

  6 months after the first administration

Secondary Outcomes (3)

• IgA secondary endpoint（EGFR ratio）

  360 days after IM19 CAR-T cell reinfusion

• IgA secondary endpoint（Urinary protein ratio）

  360 days after IM19 CAR-T cell reinfusion

• PMN secondary endpoint（Relief rate）

  360 days after IM19 CAR-T cell reinfusion

Study Arms (2)

IgA nephropathy subjects with urinary protein and renal insufficiency

EXPERIMENTAL

The study plans to recruit 6 patients with IgA nephropathy accompanied by urinary protein and renal dysfunction, including 3 patients receiving a dose of 0.5 × 10 \^ 8 CAR-T cells and 3 patients receiving a dose of 1 × 10 \^ 8 CAR-T cells

Combination Product: IM19 chimeric antigen receptor T cell injection

Primary membranous nephropathy

EXPERIMENTAL

Recruiting 6 patients with medium to high-risk PMN, including 3 patients receiving 0.5 × 10 \^ 8 CAR-T cell dose and 3 patients receiving 1 × 10 \^ 8 CAR-T cell dose, for corresponding doses of IM19 CAR-T cell infusion therapy

Combination Product: IM19 chimeric antigen receptor T cell injection

Interventions

IM19 chimeric antigen receptor T cell injection COMBINATION_PRODUCT

IgA nephropathy: The investigators plan to recruit IgA nephropathy subjects with urinary protein and renal dysfunction who meet the inclusion and exclusion criteria. They will receive Beijing Zaimiao Biological IM19 CAR-T cell infusion therapy at doses of 0.5 × 10 \^ 8 and 1 × 10 \^ 8 CAR-T cells, with 3 subjects enrolled at each dose Primary membranous nephropathy: The investigators plan to recruit primary membranous nephropathy subjects who meet the inclusion and exclusion criteria and receive IM19CAR-T cell infusion therapy at doses of 0.5 × 10 \^ 8 and 1 × 10 \^ 8 CAR-T cells, with 3 subjects enrolled at each dose

IgA nephropathy subjects with urinary protein and renal insufficiency; Primary membranous nephropathy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IgA nephropathy
• IgA nephropathy diagnosed through renal biopsy
• When screening, urine protein should be ≥0.5g/gCr and 20mL/min/1.73m\^2≤eGFR\<60mL/min/1.73m\^2
• Age≥18years old
• Liver, kidney, heart, lung function, and coagulation function meet the following requirements:
• ALT and AST ≤ 2.5 × ULN,total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert syndrome, ALT and AST ≤ 5 × ULN, total bilirubin ≤ 3 × ULN); 4.2 Left ventricular ejection fraction ≥ 50%; 4.3 International ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 4.4 Finger pulse oxygen saturation\>92% in non oxygen state;
• Women of childbearing age who have a negative blood pregnancy test before the start of the trial and agree to take effective contraceptive measures during the trial period until the last follow-up; Male participants with reproductive partners agree to take effective contraceptive measures during the trial period until the last follow-up;
• Doctors evaluate patients with the optimal benefit risk ratio
• Those who voluntarily participate in this experiment and sign the informed consent form
• Primary membranous nephropathy:
• Diagnosis of primary membranous nephropathy through renal biopsy;
• Primary membranous nephropathy at medium or high risk that has not improved after 6 months of treatment with CNI and rituximab:
• Moderate risk assessment criteria 2.1.1. EGFR is normal, 24-hour urine protein is\>4g, and conservative treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers has been continuously used for 6 months or more before screening. The 24-hour urine protein has not decreased by less than 50% 2.1.2. PLA2R antibody\<50RU/mL+ 2.1.3. Low molecular weight urinary protein 2.1.4. Selectivity index\<0.15 2.1.5. Urinary immunoglobulin UIgG\<250mg/day 2.2 High risk assessment criteria 2.2.1. eGFR\<60ml/min/1.73m\^2 2.2.2. 24-hour urine protein\>4g and lasting\>6 months 2.2.3. PLA2R antibody\>150RU/mL+ 2.2.4. High molecular weight urinary protein 2.2.5. Urine immunoglobulin UigG\>250mg/day 2.2.6. Selectivity index\>0.20
• Age ≥ 18 years old;
• Liver, heart, lung function, and coagulation function meet the following requirements:

You may not qualify if:

• IgA nephropathy:
• Kidney diseases other than IgA nephropathy, as well as primary and secondary nephrotic syndrome
• After examination by the researchers, it was determined that the subjects had diseases that were not suitable for participation in this study, such as life-threatening conditions (such as catastrophic antiphospholipid syndrome, acute severe renal failure, and acute severe central nervous system disease manifestations)
• Serious complications unrelated to IgA nephropathy
• Use or increase the dosage of corticosteroids, immunosuppressants, biologics (including but not limited to CD20 monoclonal antibodies, taceptil, etc.), anticoagulants (warfarin), and n-3 fatty acids (fish oil) for the drug treatment of IgA nephropathy within 3 months
• Uncontrollable hypertension or hyperglycemia
• Perform palatal tonsillectomy within 6 months
• Study subjects with a history of alcohol or drug abuse within the past 24 weeks
• Have undergone major surgery (including joint surgery) within 24 weeks prior to screening, or plan to undergo surgery within 24 weeks after enrollment in the study
• Used other cell therapies
• Have participated in or participated in other clinical trials within the past 3 months
• Within 3 years or planning to undergo a kidney transplan
• Active hepatitis B or hepatitis C virus, defined as: subjects with positive hepatitis B B virus surface antigen (HBsAg) and/or hepatitis B B core antibody (HBcAb, Hepatitis B core antibody) and HBV DNA titer in peripheral blood higher than the lower limit of detection; Individuals with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA (HCV RNA); Syphilis infected individuals
• Active EB virus and cytomegalovirus, defined as: subjects with positive or negative IgM antibodies in EB virus serum but EBV-DNA higher than normal values; Subjects with IgM antibody positive or IgM antibody negative but CMV-DNA higher than normal in the serum of cytomegalovirus (CMV)
• Serious history of cardiovascular and cerebrovascular diseases, including but not limited to:

Sponsors & Collaborators

• Beijing Immunochina Medical Science & Technology Co., Ltd.: lead

MeSH Terms

Conditions

Glomerulonephritis, IGA; Glomerulonephritis, Membranous

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• xiangmei Chen, doctorate

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yanping Ding, doctorate

CONTACT

01062886890; dingyanping@imunopharm.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 15, 2024
• Study Start: December 13, 2024
• Primary Completion: August 4, 2025
• Study Completion (Estimated): December 20, 2026
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share