Primary Immune Thrombocytopenia
Conditions
Brief summary
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
DRUGTQB3473 Tablets
TQB3473 tablet is a selective Spleen tyrosine kinase (Syk) inhibitor.
DRUGTQB3473 Placebo
Placebo contains no active substance.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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: 1. Receipt of immunoglobulins or platelet transfusions within 2 weeks prior to randomization; 2. 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); 3. Use of rituximab or other anti-cluster of differentiation 20 (CD20) drugs within 14 weeks prior to randomization; 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable response rate: platelet counts ≥50×10^9/L | During the 24-week randomized double-blind treatment period (Weeks 14-24) | During the 24-week randomized double-blind treatment period (Weeks 14-24), platelet counts ≥50×10\^9/L in at least 4 out of the 6 protocol-specified visits (excluding rescue treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The response rate within 24 weeks of treatment | 24 weeks | ① The proportion of subjects with at least one platelet count ≥50×10\^9/L during weeks 1-24 (excluding rescue treatment). ② Among subjects with a baseline platelet count \<15×10\^9/L, the proportion of subjects with at least one platelet count ≥30×10\^9/L and an increase of ≥20×10\^9/L from baseline during weeks 1-24 (excluding rescue treatment). ③ The proportion of subjects with platelet counts at least twice the baseline level and ≥30×10\^9/L for at least two consecutive measurements during weeks 1-24 (excluding rescue treatment). |
| Time to response: The time from the initiation of treatment to the first platelet count ≥50×10^9/L | The time from the initiation of treatment to the first platelet count ≥50×10^9/L (excluding rescue treatment) | The time from the initiation of treatment to the first platelet count ≥50×10\^9/L |
| The incidence and severity of bleeding events (Weeks 1-12) | During Weeks 1-12 of the double-blind treatment period | During Weeks 1-12 of the double-blind treatment period, the incidence and severity of bleeding events as assessed by the World Health Organization (WHO) bleeding score. |
| The effectiveness rate within the first 12 weeks of treatment | Baseline to 12 weeks | ①The proportion of subjects with at least one platelet count ≥50×10\^9/L during weeks 1-12 (excluding emergency treatment).②Among subjects with a baseline platelet count \<15×10\^9/L, the proportion of subjects with at least one platelet count ≥30×10\^9/L and an increase of ≥20×10\^9/L from baseline during weeks 1-12 (excluding rescue treatment). |
| The proportion of subjects who receive rescue treatment | During the 24-week double-blind treatment period | The proportion of subjects who receive rescue treatment aimed to increase platelet counts during the 24-week double-blind treatment period. |
| The change of concomitant therapy | During the 24-week double-blind treatment period | The proportion of subjects who reduce or discontinue concomitant ITP treatments during the 24-week double-blind treatment period. |
| The incidence and severity of adverse events | 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 | The proportion of subjects experiencing adverse events and the severity of these events, with adverse events assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| The incidence and severity of bleeding events (Weeks 1-24) | During Weeks 1-24 of the double-blind treatment period | During Weeks 1-24 of the double-blind treatment period, the incidence and severity of bleeding events as assessed by the World Health Organization (WHO) bleeding score. |
Countries
China
Contacts
Primary ContactHu Zhou, Doctor
Outcome results
None listed