| Eligibility |
Inclusion Criteria:
1. Subjects voluntarily participate in this study, sign the informed consent form, and
have good compliance;
2. Subjects are aged between 18 and 75 years old, regardless of gender;
3. Within 7 days prior to the first dose, the Eastern Cooperative Oncology Group (ECOG)
performance status score is 0-2;
4. Subjects are expected to survive for more than 6 months;
5. Subjects have previously received allogeneic hematopoietic stem cell transplantation;
6. Subjects have received systemic treatment for cGVHD of =5 lines but =1 line before;
7. 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.
8. Diagnosed with glucocorticoid-resistant/dependent cGVHD based on NIH criteria, meeting
any of the following conditions:
Subjects receiving =1 mg/kg prednisone (or equivalent dose of glucocorticoids) for at least
1 week but still have disease progression (glucocorticoid-resistant cGVHD); Subjects
receiving =0.5 mg/kg/day or =1 mg/kg every other day prednisone (or equivalent dose of
glucocorticoids) for at least 4 weeks but still have persistent disease symptoms without
improvement ( glucocorticoid-resistant cGVHD); Subjects who have failed to reduce the
glucocorticoid dose twice and have increased the prednisone (or equivalent dose of
glucocorticoids) to >0.25 mg/kg/day (glucocorticoid-dependent cGVHD).
Exclusion Criteria:
1. 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.
2. Patients with acute GVHD and those with overlapping chronic GVHD.
3. 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.
4. Unable to swallow medication normally, or with gastrointestinal dysfunction, or deemed
by the investigator to potentially affect drug absorption.
5. The presence of active infection, including bacterial, fungal, viral (such as
CMV(cytomegalovirus), EBV(epstein-barr virus), etc.) or parasitic infections that
require treatment.
6. Poor diabetes control (fasting blood glucose (FBG) > 10 mmol/L).
7. Inadequate blood pressure control (systolic blood pressure =150mmHg or diastolic blood
pressure =100 mmHg).
8. 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).
9. At the time of screening, forced expiratory volume in 1 second (FEV1) = 39% or NIH
pulmonary symptom score of 3.
10. 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.
11. Patients receiving treatment with Ibrutinib or Ruxolitinib within the past 28 days
prior to the first administration of the study drug (except those who have completed
washout prior to the first administration of the study drug) are excluded from
participation in the study.
12. Patients who participated in other drug or device clinical trials within 4 weeks prior
to the screening visit (or 5 half-lives, whichever is longer).
13. Patients receiving treatment with Warfarin or any other coumarin derivative
anticoagulant, or patients with a bleeding tendency or coagulation disorder.
14. Patients with positive HBsAg and/or HBcAb and positive HBV-DNA (HBV-DNA negative
patients are eligible); patients with positive HCV (hepatitis C virus) antibody and
HCV-RNA copy number above the lower limit of detection. Note: Eligible patients with
positive hepatitis B surface antigen or hepatitis B core antibody, and patients with
hepatitis C, require continuous antiviral therapy to prevent virus activation.
15. Patients with positive HIV antibody.
16. Patients who have previously received treatment with a ROCK2 inhibitor.
17. Patients with a known history of severe allergic reactions to the study drug or its
major ingredients.
18. Pregnant or breastfeeding women.
19. Patients with known alcohol or drug dependence.
20. Any other reason that the investigator believes may prevent a patient from
participating in the study.
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