Inaticabtagene Autoleucel Injection in the Treatment of Refractory Systemic Lupus Erythematosus-related Immune Thrombocytopenia

Official title

A Multi-center, Open-label, Single-arm Phase I Clinical Study to Evaluate the Safety and Tolerability of Inaticabtagene Autoleucel Injection in Treatment of Refractory Systemic Lupus Erythematosus-related Immune Thrombocytopenia

Overview

This is a single-arm, open-label，phase I clinical study to evaluate the safety and tolerability of Inaticabtagene Autoleucel Injection in treatment of refractory systemic lupus erythematosus-related immune thrombocytopenia.

Detailed description

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and tolerability of Inaticabtagene Autoleucel Injection in treatment of refractory systemic lupus erythematosus-related immune thrombocytopenia and determine the Phase II Recommended Dose (RP2D). The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation \& Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total duration of the study is 2 years from Inaticabtagene Autoleucel Injection infusion.

Interventions

• Drug Inaticabtagene autoleucel Injection
  Inaticabtagene autoleucel Injection, the autologous 2nd generation CD19-directed CAR-T cells, will be administered by vein. Before CAR-T infusion，patients will get a 3-4 days lymphodepletion therapy with fludarabine and cyclophosphamide.

Primary outcome measures

• Incidence of Treatment-related Adverse Events [Time frame: Up to 28 days post-infusion]
• The safe dosage for a single infusion of Inaticabtagene Autoleucel Injection [Time frame: Up to 28 days post-infusion]

Secondary outcome measures (9)

• Overall Remission Rate (ORR) [Time frame: Up to 6 months post-infusion]
• Proportion of subjects who achieved disease remission (DORIS) [Time frame: Up to 6 months post-infusion]
• Proportion of subjects who achieved lupus hypoactivity state (LLDAS) [Time frame: Up to 6 months post-infusion]
• Improvement in systemic lupus erythematosus scores (SELENA-SLEDAI) [Time frame: Up to 24 months post-infusion]
• Changes in MOS item short from health survey(SF-36) [Time frame: Up to 24 months post-infusion]
• Changes in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) [Time frame: Up to 24 months post-infusion]
• Changes in serological markers [Time frame: Up to 24 months post-infusion]
• Changes in serological markers [Time frame: Up to 24 months post-infusion]
• Reduction of Combination therapy evaluation [Time frame: Up to 24 months post-infusion]

Eligibility criteria

Inclusion criteria

• Age range: 18-70 years (including 18 and 70 years), regardless of gender.
• Clinically diagnosed with Refractory Systemic Lupus Erythematosus-related Immune Thrombocytopenia according to the revised criteria of ACR in 1997 or EULAR/ACR in 2019. At least two consecutive blood routine tests showing platelet counts <50×10\^9/L; Peripheral blood smear microscopy showed no significant abnormalities in the morphology of blood cells; The morphological characteristics of bone marrow cells are consistent with immune thrombocytopenia. Treated at least 1 course of MP shock therapy or high-dose steroids, combined with one or more immunosuppressive agents (including biologics) for at least 3 months but not achieving partial remission, or the efficacy cannot be maintained during the steroid reduction process.
• During the study period, the use of corticosteroids at a dose not exceeding 10mg prednisone or its equivalent, all immunosuppressants (excluding hydroxychloroquine) should be discontinued.
• Women of childbearing potential must have a negative blood pregnancy test 7 days prior to trial conditioning therapy; any male and female patients of childbearing potential must agree to use an effective method of contraception throughout the study and for at least 2 year following infusion of CAR-T cells. Childbearing potential is biologically capable of bearing a living baby and sexually active. Female patients who were not of childbearing potential (ie, met at least 1 of the following criteria):

• Hysterectomy or oophorectomy, or
• Medically confirmed ovarian failure, or medically confirmed postmenopausal (cessation of menses for at least 12 consecutive months in the absence of pathological or physiological causes).
• Adequate organ function according to the following criteria:

• Aspartate aminotransferase (AST) ≤ 3 times of upper limit of normal (ULN);
• Alanine aminotransferase (ALT) ≤ 3 times ULN;
• Total serum bilirubin ≤ 2 times ULN unless the patient has documented Gilbert's syndrome; patients with Gilbert's syndrome who have bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included;
• Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula), Patients with lupus nephritis may relax the conditions appropriately according to the judgment of the investigator;
• Must have minimal pulmonary reserve and oxygen saturation > 91% in a nonoxygenated state;
• Lymphocyte count > 0.4 × 109/L.

Exclusion criteria

• Severe active central nervous system (CNS) lupus, including seizures, psychosis, cerebrovascular accidents, or CNS vasculitis requiring therapeutic intervention within 60 days after baseline.
• Dialysis patients or creatinine clearance rate less than 30mL/min.
• Pregnancy or breastfeeding.
• Merge active infections (such as sepsis, bacteremia, mycosis, uncontrolled lung infections, and active tuberculosis).
• Hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) are positive; Hepatitis B e antibody (HBe Ab) and/or hepatitis B core antibody (HBcAb) are positive, and the number of HBV-DNA copies is greater than the measurable lower limit; Hepatitis C (HCV) antibody positive; positive for human immunodeficiency virus (HIV) antibodies; positive for syphilis antibody (TP Ab);
• Major surgery that was assessed as unsuitable by the investigators within 4 weeks before screening.
• Patients with concurrent active malignancy within the past five years, those with a history of malignancy but cuired are eligible.
• The patient's heart meets any of the following conditions:

Left ventricular ejection fraction (LVEF) ≤ 45%; New York Heart Association (NYHA) Grade III or IV congestive heart failure or active heart disease; Severe arrhythmias that require treatment (excluding atrial fibrillation and paroxysmal supraventricular tachycardia); QTcB interval ≥ 450ms for males and ≥ 470ms for females (QTcB=QT/RR1/2); Have had myocardial infarction, bypass or stent surgery within the 6 months prior to the study; Other heart diseases that have been determined by researchers to be unsuitable for inclusion;

• Patients with clinically significant pleural effusion during screening.
• Patients vaccinated with a live vaccine within 6 weeks prior to screening.
• Patients with deep vein thrombosis within 6 months prior to screening, or a history of pulmonary embolism.
• Patients with a life expectancy of less than 6 months.
• Patients participating in any other interventional clinical study or receiving treatment of an active investigational drug within 3 months or 5 half-lives for launched drugs prior to Inaticabtagene Autoleucel Injection infusion.
• Patients with a history of epilepsy, cerebral ischemia/hemorrhage, cerebellar diseases, or other active central nervous system disorders;
• Patients with hypersensitivity reactions to the components of Inaticabtagene Autoleucel Injection.
• Patients previously received CAR-T cell therapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Identifiers

NCT: NCT06826430 · HY001105

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗