Safety and Efficacy of PRG-1801 in Recurrent/Refractory Primary Immune Thrombocytopenia (ITP)

NCT06519565 | Recruiting Early Phase 1

• 1 other identifier: PRG1801E13
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Immune Thrombocytopenia

Outcome Measures

Primary Outcomes (2)

• 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)

  Up to 28 days post-infusion

• 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).

  Up to 28 days post-infusion

Secondary Outcomes (3)

• Complete response (CR) rate or Response (R) rate of administering PRG-1801 in the treatment of relapsed/refractory ITP

  At Day 28, Month 2, Month 3, Month 6,Month 9, Month 12, Month 18, and Month 24 post-infusion

• The proliferation rate and persistence time of CAR-T cells

  At baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18, and Month 24 post-infusion

• Concentration of serum sBCMA, immunoglobulins (IgG, IgM, IgA), and anti-platelet glycoprotein autoantibodies

  At baseline, Day 28, Month 2, Month 3, Month 6,Month 9, Month 12, Month 18, and Month 24 post-infusion

Other Outcomes (1)

• Evaluation of incidence of Treatment-related Adverse Events and Complete response rate or Response rate of repeated PRG-1801 infusion

  Up to 24 months after second infusion

Study Arms (1)

PRG-1801(BCMA-targeting CAR-T Cells)

EXPERIMENTAL

The study was structured into two distinct phases: the dose exploration phase and the dose expansion phase. During the dose exploration phase, three dosage levels were established-100x10\^6 CAR-T and 200x10\^6 CAR-T-with each dosage group comprising 3 to 6 subjects with Immune Thrombocytopenia (ITP). If dose-limiting toxicity (DLT) was observed in one out of three subjects within any dosage group, an additional three subjects were enrolled at the same dosage level. Should DLT be present in two or more out of six subjects, considerations for dose reduction or potential study discontinuation were made. Upon determining the safe and effective fixed dose of PRG-1801 during the dose exploration phase, the study progressed to the dose expansion phase. This subsequent phase involved enrolling an additional 3 to 6 subjects at the established fixed dose. The aim was to further assess and confirm the safety and efficacy of this specific dose for treating ITP.

Drug: PRG-1801

Interventions

PRG-1801 DRUG

PRG-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.

Also known as: BCMA-targeting CAR-T Cells

PRG-1801(BCMA-targeting CAR-T Cells)

Eligibility Criteria

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

You may qualify if:

• \. Age ≥18 years, regardless of gender.
• \. 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.
• \. Positive for anti-platelet glycoprotein autoantibodies (such as GPIIb/IIIa).
• \. 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.
• \. Basic normal function of important organs:
• Echocardiography indicates an ejection fraction ≥50%, and the electrocardiogram shows no significant abnormalities.
• Creatinine clearance rate (CrCl) (Cockcroft-Gault formula) ≥30 mL/min.
• Alanine transaminase (ALT) and aspartate transaminase (AST) ≤3.0× the upper limit of normal (ULN).
• Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤2.0×ULN (Gilbert's syndrome ≤ 3.0×ULN).
• Absolute lymphocyte count (ALC) ≥0.5×10\^9/L; absolute neutrophil count (ANC) ≥1×10\^9/L; hemoglobin (Hb) ≥60 g/L; platelet count ≥10×10\^9/L.
• Blood oxygen saturation \>92%.
• \. Meet the standards for apheresis or venous blood collection, and have no contraindications to cell collection.
• \. Men of reproductive potential and women of childbearing age must agree to use effective contraception from the signing of the informed consent form until 1 year after the use of the study drug. Blood pregnancy tests for women of childbearing age must be negative at screening and before cell infusion, and they must not be breastfeeding.
• \. The participant or their guardian agrees to participate in this clinical trial and signs the informed consent form (ICF), indicating their understanding of the purpose and procedures of this clinical trial and their willingness to participate in the study.

You may not qualify if:

• \. Thrombocytopenia caused by myelodysplastic syndromes, early aplastic anemia, atypical aplastic anemia, thrombotic thrombocytopenic purpura, etc.
• \. 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.
• \. Allergic history to any component in the cell product.
• \. Suffering from any of the following heart diseases:
• Congestive heart failure of NYHA class III or IV.
• Myocardial infarction or coronary artery bypass grafting (CABG) or coronary stent implantation within ≤6 months before signing the ICF.
• Clinically significant ventricular arrhythmias, or history of unexplained syncope (excluding vasovagal syncope or dehydration).
• Severe non-ischemic cardiomyopathy history.
• \. Malignant tumors within the past 3 years before screening, except for the following: malignant tumors that have been treated radically and have no known active disease for ≥3 years before enrollment; or well-treated non-melanoma skin cancer with no evidence of disease.
• \. Symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months or currently requiring anticoagulant therapy.
• \. Participation in other interventional clinical studies within 1 month before screening.
• \. Vaccination with attenuated live vaccines within 4 weeks before screening.
• \. Stroke or epileptic seizure within 6 months before signing the ICF (excluding old lacunar cerebral infarction).
• \. The following treatments before CAR-T reinfusion: immunosuppressive treatment within 3 days; use of prednisone (or equivalent drugs) at a dose \>10mg/day within 3 days.
• \. The following treatments before CAR-T reinfusion: treatment with B-cell depleting agents such as rituximab within 24 weeks (unless B cells have recovered); immunoglobulin reinfusion treatment within 4 weeks.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Shenzhen Pregene Biopharma Co., Ltd.: collaborator

Study Sites (2)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• Heng Mei, Ph.D&M.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei, Ph.D&M.D

CONTACT

027-8572600; hmei@hust.edu.cn

Jinhui Shu, Ph.D

CONTACT

18326016087; sjh18326016087@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: PRG-1801 Injection

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 25, 2024
• Study Start: August 20, 2024
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): August 15, 2027
• Last Updated: November 28, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)