A Study of TQB3473 Tablets Compared to Placebo in the Treatment of Adult Primary Immune Thrombocytopenia

Official title

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQB3473 Tablets Compared to Placebo in the Treatment of Adult Primary Immune Thrombocytopenia (ITP)

Overview

This is a randomized, double-blind, placebo-controlled Phase III clinical study designed to demonstrate that TQB3473 tablets significantly improve the sustained response rate compared to placebo in adult patients with chronic ITP who have previously received standard corticosteroid therapy and have failed or relapsed after at least one standard ITP treatment. The study consists of a treatment period and a safety follow-up period.

Interventions

• Drug TQB3473 Tablets
  TQB3473 tablet is a selective Spleen tyrosine kinase (Syk) inhibitor.
• Drug TQB3473 Placebo
  Placebo contains no active substance.

Primary outcome measures

• Durable response rate: platelet counts ≥50×10^9/L [Time frame: During the 24-week randomized double-blind treatment period (Weeks 14-24)]

Secondary outcome measures (8)

• The effectiveness rate within the first 12 weeks of treatment [Time frame: Baseline to 12 weeks]
• The response rate within 24 weeks of treatment [Time frame: 24 weeks]
• Time to response: The time from the initiation of treatment to the first platelet count ≥50×10^9/L [Time frame: The time from the initiation of treatment to the first platelet count ≥50×10^9/L (excluding rescue treatment)]
• The incidence and severity of bleeding events (Weeks 1-12) [Time frame: During Weeks 1-12 of the double-blind treatment period]
• The incidence and severity of bleeding events (Weeks 1-24) [Time frame: During Weeks 1-24 of the double-blind treatment period]
• The proportion of subjects who receive rescue treatment [Time frame: During the 24-week double-blind treatment period]
• The change of concomitant therapy [Time frame: During the 24-week double-blind treatment period]
• The incidence and severity of adverse events [Time frame: From the signing of the informed consent until 28 days after the last dose of study drug or the initiation of new ITP treatment, whichever occurs first]

Eligibility criteria

Inclusion criteria

• Subjects voluntarily join this study, sign the informed consent form (ICF), and demonstrate good compliance;
• Male or female subjects aged 18 to 75 years (calculated based on the date of signing the informed consent form);
• Eastern Cooperative Oncology Group (ECOG) score of 0-1;
• Diagnosis of primary ITP prior to randomization, with a duration of ≥12 months;
• An average of at least three independent platelet counts (spaced more than 3 days apart) within the 3 months prior to randomization <30×10\^9/L, with no count >35×10\^9/L; and no severe bleeding within 4 weeks prior to screening;
• Previous treatment with glucocorticoids and at least one standard ITP therapy that was ineffective or resulted in relapse.
• Female subjects of childbearing potential must agree to use effective contraception during the study and for 6 months after the end of study treatment, with a negative serum or urine pregnancy test within 7 days prior to study enrollment; male subjects must agree to use effective contraception during the study and for 6 months after the end of study treatment, as detailed in Section 5.5.

Exclusion criteria

• Evidence of secondary causes of ITP (e.g., untreated Helicobacter pylori infection, leukemia, lymphoma, history of autoimmune diseases such as systemic lupus erythematosus, Hashimoto's thyroiditis, etc.) or drug-induced causes (e.g., anticonvulsants, antibiotics, heparin, etc.), or immune-mediated cytopenia involving two or more cell lines such as Evans syndrome or immune-related cytopenia;
• Subjects with a history or current diagnosis of myelofibrosis, myelodysplastic syndrome, aplastic anemia, lymphoproliferative disorders, or other malignant hematologic diseases;
• History of or concurrent other malignancies within the past 3 years. Exceptions include: other malignancies treated with a single surgical procedure and achieving continuous 5-year disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)\];
• Conditions affecting venous blood sampling or multiple factors affecting oral medication (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
• Adverse reactions from previous treatments have not resolved to ≤CTCAE grade 1, except for non-clinically significant and asymptomatic laboratory abnormalities judged by the investigator to pose no safety risks;
• Previous bone marrow/hematopoietic stem cell transplantation or major solid organ transplantation;
• Vaccination within 8 weeks prior to randomization or planned vaccination during the study period;
• Major surgical treatment or significant traumatic injury within 4 weeks prior to randomization, or anticipated need for major elective surgery during the study treatment period (major surgery is defined as level 3 or higher according to the National Surgical Classification Catalog 2022);
• History of intracranial hemorrhage or other severe bleeding in vital organs (≥CTCAE grade 3), or symptomatic gastrointestinal bleeding (e.g., hematemesis, melena, etc., excluding asymptomatic "occult blood test positive" and hemorrhoids) within 6 months prior to screening;
• Arterial/venous thrombotic events within 12 months prior to randomization, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism;
• ITP-related symptoms and treatments:

• Receipt of immunoglobulins or platelet transfusions within 2 weeks prior to randomization;
• Receipt of treatments aimed at increasing platelet counts (including but not limited to glucocorticoids, Thyroid peroxidase (TPO), Thrombopoietin receptor agonists (TPO-RAs), cyclosporine, herbal medicines, etc.) within 4 weeks prior to randomization, except for those meeting inclusion criterion (8);
• Use of rituximab or other anti-cluster of differentiation 20 (CD20) drugs within 14 weeks prior to randomization;
• Splenectomy within 12 weeks prior to randomization.
• Need for long-term/continuous use of medications affecting platelet function \[including but not limited to aspirin, clopidogrel, ticagrelor, non-steroidal anti-inflammatory drugs (NSAIDs), etc.\] or anticoagulant therapy;
• Known allergy to the active ingredient or excipients of the investigational drug;
• Previous treatment with Syk inhibitors;
• Participation in another clinical trial and use of investigational drugs within 4 weeks prior to randomization;
• Any condition judged by the investigator to pose a significant risk to the subject's safety or to affect the subject's ability to complete the study.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 53 centers

• The first affiliated hospital of ustc anhui provincial hospital — Hefei
• The First Affiliated Hospital of Wannan Medical College — Wuhu
• Beijing Chaoyang Hospital, Capital Medical University — Beijing
• Peking Union Medical College Hospital — Beijing
• The Second Affiliated Hospital of Chongqing Medical University — Chongqing
• The First Hospital of Lanzhou University — Lanzhou
• Nanfang Hospital, Southern Medical University — Guangzhou
• Shenzhen Nanshan People's Hospital — Shenzhen
• … and 45 more centers

Identifiers

NCT: NCT06900920 · TQB3473-III-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗