TDI01 for Treatment of Moderate or Severe Chronic Graft-Versus-Host Disease After Failure of at Least 1 and Not More Than 5 Lines of Systemic Therapy: an Open Label, Multi-center, ph1/2 Study
Overview
- Phase
- Phase 1
- Intervention
- TDI01 suspension
- Conditions
- GVHD, Chronic
- Sponsor
- Beijing Tide Pharmaceutical Co., Ltd
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Phase Ib study stage:The best overall response rate (BORR)
- Status
- Active, not recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
-
Phase Ib study stage:
Primary objective: To evaluate the efficacy and safety Secondary objectives: To evaluate the population pharmacokinetic characteristics
-
Phase II study stage:
Primary objective: To evaluate the efficacy Secondary objectives: To evaluate the safety
Detailed Description
1. Phase Ib study stage: Primary objective: To evaluate the efficacy and safety of TDI01 suspension in treating patients with moderate or severe Chronic Graft-Versus-Host Disease after failure of at least 1 and not more than 5 lines of systemic therapy Secondary objectives: To evaluate the population pharmacokinetic characteristics of TDI01 suspension in treating patients with moderate or severe Chronic Graft-Versus-Host Disease after failure of at least 1 and not more than 5 lines of systemic therapy. 2. Phase II study stage: Primary objective: To evaluate the efficacy of TDI01 suspension in treating patients with moderate or severe Chronic Graft-Versus-Host Disease after failure of at least 1 and not more than 5 lines of systemic therapy Secondary objectives: To evaluate the safety of TDI01 suspension in treating patients withmoderate or severe Chronic Graft-Versus-Host Disease after failure of at least 1 and not more than 5 lines of systemic therapy as well as the population pharmacokinetic characteristics of TDI01 suspension in treating these patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance;
- •Subjects are aged between 18 and 75 years old, regardless of gender;
- •Within 7 days prior to the first dose, the Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2;
- •Subjects are expected to survive for more than 6 months;
- •Subjects have previously received allogeneic hematopoietic stem cell transplantation;
- •Subjects have received systemic treatment for cGVHD of ≤5 lines but ≥1 line before;
- •Diagnosed with moderate to severe cGVHD based on NIH criteria, defined as follows:
- •Moderate cGVHD: involvement of ≥3 organs with organ scores of 1 point, or involvement of ≥1 organ (excluding the lung) with organ scores of 2 points, or involvement of the lung with organ scores of 1 point; Severe cGVHD: involvement of ≥1 organ (excluding the lung) with organ scores of 3 points, or involvement of the lung with organ scores of 2 points or higher.
- •Diagnosed with glucocorticoid-resistant/dependent cGVHD based on NIH criteria, meeting any of the following conditions:
- •Subjects who have received at least 2 lines but no more than 5 lines in the past are required to have stable systemic therapy (such as corticosteroids, calcineurin inhibitors, sirolimus, mycophenolate mofetil (MMF), methotrexate, and extracorporeal phototherapy (ECP)) for at least two weeks prior to screening.
Exclusion Criteria
- •The presence of recurrence of the primary disease, or having received treatment for recurrence of the primary disease after allo-HSCT（Hematopoietic stem cell transplant）, or the possible need for rapid immunosuppressive drug withdrawal as emergency treatment for early recurrence of malignant tumors; or the presence of post-transplant lymphoproliferative disorders.
- •Patients with acute GVHD and those with overlapping chronic GVHD.
- •Patients who have suffered from other malignant tumors except for the transplanted tumor within the past 3 years, with the exception of locally curable cancers (i.e., those that have already been cured), such as basal cell carcinoma or squamous cell carcinoma of the skin, cervical or breast carcinoma in situ, or superficial bladder cancer.
- •Unable to swallow medication normally, or with gastrointestinal dysfunction, or deemed by the investigator to potentially affect drug absorption.
- •The presence of active infection, including bacterial, fungal, viral (such as CMV(cytomegalovirus), EBV(epstein-barr virus), etc.) or parasitic infections that require treatment.
- •Poor diabetes control (fasting blood glucose (FBG) \> 10 mmol/L).
- •Inadequate blood pressure control (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100 mmHg).
- •History of myocardial infarction within 6 months prior to planned initiation of TDI01 treatment, or arrhythmia (CTC AE(adverse event) grade 2 or higher, including QTcF ≥450ms (men), QTcF ≥470ms (women)) and congestive heart failure grade ≥2 (New York Heart Association (NYHA) classification).
- •At the time of screening, forced expiratory volume in 1 second (FEV1) ≤ 39% or NIH pulmonary symptom score of
- •Received systemic treatment for cGVHD within 14 days prior to enrollment; if the dose/regimen of systemic treatment has been stable for at least 2 weeks prior to screening (corticosteroids, calcineurin inhibitors, sirolimus, mycophenolate mofetil (MMF), methotrexate, and extracorporeal photopheresis (ECP)), it is allowed.
Arms & Interventions
200mg
200mg oral once a day
Intervention: TDI01 suspension
400mg
400mg oral once a day
Intervention: TDI01 suspension
200mg or 400mg
200mg or 400mg oral once a day
Intervention: TDI01 suspension
Outcomes
Primary Outcomes
Phase Ib study stage:The best overall response rate (BORR)
Time Frame: 24 weeks.
The best overall response rate (BORR) at 24 weeks.
Phase Ib study stage:adverse events
Time Frame: 24 weeks.
The incidence of adverse events, including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and treatment-related adverse events (TRAEs).
Phase II study stage:The best overall response rate (BORR)
Time Frame: 24 weeks.
The best overall response rate (BORR) at 24 weeks.