A Study of RJMty19 in Refractory Systemic Lupus Erythematosus (SLE)

NCT06340490 | Not Yet Recruiting Phase 1

• 1 other identifier: RJMty19-AID002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

This study is an open-label, single-arm, dose escalation and dose expansion study to evaluate the safety, maximum tolerated dose, pharmacokinetic characteristics of allogeneic CD19-CAR-DNT cells (RJMty19) after infusion, and preliminary efficacy in systemic lupus erythematosus (SLE) subjects.

Conditions

Systemic Lupus Erythematosus

Keywords

off-the-shelf cell product; CAR-DNT; Cell Therapy; Autoimmune Disease

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  To evaluate the safety, tolerability, and determine the recommended dosage of RJMty19 for SLE subjects

  Up to 28 days

• Maximum Tolerated Dose (MTD)

  MTD is the highest dose for DLT in ≤1/6 subjects

  Up to 28 days

• Incidence of abnormalities

  Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.

  Up to 28 days

Secondary Outcomes (5)

• Pharmacokinetics (PK) indicator (Cmax)

  Up to 28 days

• Pharmacokinetics (PK) indicator (AUC)

  Up to 90 days

• Pharmacokinetics (PK) indicator (CAR copy numbers)

  Up to 24 months

• Remission rate of SLE based on DORIS criteria

  at 3 months, 6 months, 12 months and 24 months

• Remission rate of SLE based on LLDAS criteria

  at 3 months, 6 months, 12 months and 24 months

Study Arms (1)

RJMty19 (CD19-CAR-DNT Cells)

EXPERIMENTAL

The trial is divided into two parts: Part A is a dose escalation trial with three dose groups (5×10\^6 CAR+ cells/kg, 1×10\^7 CAR+ cells/kg, 2×10\^7 CAR+ cells/kg at day 0), with 9-18 patients planned to be enrolled. Part B is a dose-expansion trial in which 3\~6 patients will receive RJMty19 infusions at RP2D dose levels

Biological: RJMty19 (CD19-CAR-DNT cells)

Interventions

RJMty19 (CD19-CAR-DNT cells) BIOLOGICAL

Lentiviral vector-transducted double negative T cells (DNT) to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy.

Also known as: Fludarabine, Cyclophosphamide

RJMty19 (CD19-CAR-DNT Cells)

Eligibility Criteria

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

You may qualify if:

• Voluntarily sign an ICF and expect to complete the subsequent follow-up.
• Age 18～65 years old (including cut-off value), gender is not limited.
• Diagnosed with SLE according to the 2019 EULAR/ACR version of the revised criteria.
• Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥ 8 points; Anti-nuclear antibody titer ANA≥1:80, or positive anti-dsDNA and/or anti-Sm antibodies.
• Presence of active organ involvement.
• Having appropriate organ function, and the laboratory test results within 7 days before the lymphodepletion must meet the following criteria:
• Coagulation function:
• Fibrinogen ≥1.0 g/L;
• Activated partial thromboplastin time ≤ 1.5 times the upper limit of normal (ULN);
• Prothrombin time (PT) ≤ 1.5 times ULN.
• Liver function:
• Glutathione aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN);
• Glutamic aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN);
• Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome;
• Subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included.

You may not qualify if:

• Other malignancies within 5 years prior to screening, except adequately treated non-melanoma skin cancer (basal cell carcinoma or squamous cell carcinoma) or carcinoma in situ of the cervix;
• Major surgery requiring hospitalization within 4 weeks prior to screening or during screening;
• History of severe drug allergies or anaphylactic constitution;
• Renal disease: Diagnosed with active severe lupus nephritis within 8 weeks prior to screening, requiring treatment with drugs prohibited by the study protocol for the treatment of active nephritis, hemodialysis or prednisone dose ≥ 100 mg/d, or equivalent glucocorticoids for ≥14 days; Creatinine clearance rate \< 60mL/min and serum creatinine \> 1.5 times ULN within 1 week before lymphodepleting chemotherapy;
• Central nervous system diseases: those with active central nervous system diseases caused by SLE or non-SLE (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis);
• Cardiovascular disease: unstable angina, myocardial infarction, New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (The definition of refractory hypertension is: on the basis of improving lifestyle, reasonable and tolerable use of ≥3 antihypertensive drugs (including diuretics) for more than 1 month, blood pressure still not reached the target (systolic blood pressure≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg) or taking ≥4 antihypertensive drugs to effectively control blood pressure) and a history of severe arrhythmias requiring medication;
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer test higher than the lower limit of the detection value, hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive, human immunodeficiency virus (HIV) antibody positive, cytomegalovirus (CMV) DNA test positive, syphilis test positive;
• Presence of active or uncontrollable infection requiring systemic treatment (other than simple urinary tract infection or upper respiratory tract infection) and currently receiving suppressive therapy for any chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); untreated latent tuberculosis infection;
• There is clinical evidence showing the presence of important, unstable, or uncontrolled acute or chronic diseases not caused by SLE (i.e. cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignant tumors, or infectious diseases), which researchers believe may confound the study results or expose subjects to unnecessary risks;
• Vaccination with live or attenuated live vaccine within 1 month before screening;
• History of/preparing to undergo organ transplantation or hematopoietic stem cell transplantation;
• Received CAR-T therapy or other gene-modified cell therapy prior to enrolment;
• Have received any of the following treatments for SLE:
• Use of therapeutic doses of corticosteroids (defined as prednisone or equivalent\> 20 mg/d) within 72 hours prior to lymphodepleting chemotherapy or RJMty19 infusion;
• Treatment of SLE with any other clinical investigational agent within 4 weeks prior to enrollment. However, enrollment is allowed if the study treatment period is ineffective or the disease has progressed, and at least 3 half-lives have elapsed prior to enrollment;

Sponsors & Collaborators

• Guangdong Ruishun Biotech Co., Ltd: lead
• RenJi Hospital: collaborator
• Peking University People's Hospital: collaborator
• Changhai Hospital: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator

Study Sites (4)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200001, China

Location

Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Shuang Ye, MD, PhD

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

• Zhanguo Li, MD, PhD

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haicun Xie

CONTACT

+086-18358586096; hcxie@wyzebiotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: April 1, 2024
• Study Start: May 15, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 1, 2024

Record last verified: 2024-03

Locations

CN (4)