This is a single center, open-label, 3+3 dose escalation, early phase 1 study to evaluate the safety, tolerability, and preliminary efficacy of PRG-1801 for patients with relapsed/refractory immune thrombocytopenia (ITP).
1. Age ≥18 years, regardless of gender.
2. Clinically diagnosed with primary immune thrombocytopenia for at least 6 months, with a platelet count <30×10^9/L within 48 hours before participating in the study.
3. Positive for anti-platelet glycoprotein autoantibodies (such as GPIIb/IIIa).
4. Previously received first-line and/or second-line ITP treatment (first-line treatment includes: corticosteroids or immunoglobulins; second-line treatment includes thrombopoietin receptor agonists (such as eltrombopag, romiplostim) and/or rituximab, etc.), but the treatment was ineffective (platelet count <30×10^9/L after treatment, or platelet count did not increase to twice the baseline value, or there was bleeding), or relapsed after effective treatment (platelet count dropped below 30×10^9/L after effective treatment, or dropped to less than twice the baseline value, or bleeding symptoms occurred) or difficult to maintain after stopping TPO receptor agonists.
1. Thrombocytopenia caused by myelodysplastic syndromes, early aplastic anemia, atypical aplastic anemia, thrombotic thrombocytopenic purpura, etc.
2. Bone marrow examination during the screening period suggests myelofibrosis MF≥2 (European consensus scoring standard Thieleja2005) or bone marrow examination indicates the presence of primary diseases other than ITP that can cause thrombocytopenia.
3. Allergic history to any component in the cell product.
Congestive heart failure of NYHA class III or IV.
Single group
PRG-1801
DrugPRG-1801 is a chimeric antigen receptor T-cell (CAR-T) therapy targeting BCMA. Participants will undergo leukapheresis to collect mononuclear cells for PRG-1801 manufacturing. Prior to infusion, patients receive lymphodepletion with cyclophosphamide (250-300 mg/m2/day) and fludarabine (25-30 mg/m2/day) for 3 days. PRG-1801 is then administered as a single intravenous infusion at one of three dose levels: 100×10\^6, or 200×10\^6 CAR-T cells. Premedication with antipyretics and antihistamines is given 30-60 minutes before infusion. The infusion rate is 2-5 ml/min. Patients are monitored for safety and efficacy for up to 24 months post-infusion. Some patients may be eligible for a second infusion if they respond initially but later relapse.
Incidence of Treatment-related Adverse Events
Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
The safe dosage for a single infusion of PRG-1801
The safe PRG-1801 infusion dosage for ITP patients will be evaluated by comprehensively assessing the complete response (CR) rate and the incidence of adverse events (AEs).
Complete response (CR) rate or Response (R) rate of administering PRG-1801 in the treatment of relapsed/refractory ITP
CR is defined as platelet count ≥100×10\^9/L. R is defined as platelet count ≥30×10\^9/L and at least doubling from baseline, without active bleeding.
The proliferation rate and persistence time of CAR-T cells
Evaluation of CAR-T cell expansion and persistence through measurement of CAR copy number in peripheral blood
Concentration of serum sBCMA, immunoglobulins (IgG, IgM, IgA), and anti-platelet glycoprotein autoantibodies
Pharmacodynamics of PRG-1801 were assessed by evaluating changes from baseline in serum sBCMA, immunoglobulins (IgG, IgM, IgA), and anti-platelet glycoprotein autoantibodies
Evaluation of incidence of Treatment-related Adverse Events and Complete response rate or Response rate of repeated PRG-1801 infusion
The evaluation metrics are the same as those for the primary and secondary outcome measures of single infusion.
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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Lead sponsor
Shenzhen Pregene Biopharma Co., Ltd.
Collaborator
