A Study of TQ05105 in Patients With Chronic Graft Versus Host Disease

Study Overview
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Brief Summary
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This study was a single arm, open label, multicenter phase Ib / II trial in subjects with glucocorticoid refractory / dependent moderate to severe cGVHD.The trial consisted of two phases: phase I for the dose exploration and phase II for the extension study.

Official Title
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A Single Group, Open-Label, Multicenter ,Phase Ib/II Clinical Trials of TQ05105 Tablet in Patients With Glucocorticoid Refractory and Dependent Moderate to Severe Chronic Graft Versus Host Disease (cGVHD).

Conditions
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Chronic Graft Versus Host Disease

Intervention / Treatment
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* Drug: TQ05105 Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understood and signed an informed consent form. ≥18 years old, Karnofsky Performance Scale of ≥60, life expectancy ≥ 6 months. Has received allogeneic hematopoietic stem cell transplantation (alloSCT). Clinically diagnosed moderate to severe cGVHD according to NIH Consensus Criteria. Has received systemic or topical corticosteroids therapy and confirmed steroid-refractory/dependent cGVHD according to NIH Consensus Criteria. Has received at least 1 lines of therapy for cGVHD. Adequate laboratory indicators. No pregnant or breastfeeding women, and a negative pregnancy test. Exclusion Criteria: Has active acute GVHD. Has previously failed to respond to JAK inhibitors for GVHD, or who had used JAK inhibitors within 4 weeks before the first administration. Has uncontrollable active infections or infections requiring systematic treatment within 7 days before the first administration. Development of other basic diseases. Has malignant tumors within 3 years. Has multiple factors affecting oral medication. Has substance abuse or a psychotic disorder. Has severe and / or uncontrolled disease. Allergic to drugs or its constituents. Has participated in any other clinical trials within 4 weeks before first administration. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQ05105 Tablet<br>TQ05105 tablet 10mg given orally, twice daily in 28-cycle. | Drug: TQ05105 Tablet<br>* TQ05105 tablet is a Janus Kinase (JAK) inhibitor, which can inhibit the abnormal activation of JAK 2-V617F mutation, thereby inhibiting the sustained abnormal activation of JAK / STAT pathway.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Tolerable Dose (MTD) | If dose limiting toxicity (DLT) occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD. (Patients in phase Ib) | Baseline up to 4 weeks | 
| Recommended phase II dose (RP2D) | Recommended dose for phase II (Patients in phase Ib) | Baseline up to 4 weeks | 
| Best Overall Response Rate (BOR) | Percentage of participants achieving complete response (CR) and partial response (PR). (Patients in phase II) | Baseline up to 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR) during the study according to the cGVHD NIH Consensus Criteria. | Baseline up to 52 weeks | 
| Duration of Response (DOR) | DOR defined as time from earliest date of disease response to earliest date of disease progression. | Baseline up to 96 weeks | 
| Overall survival (OS) | OS defined as the time from randomization to the time of death from any cause. | Baseline up to death event, up to 5 years. | 
| Non-relapse mortality (NRM) | Defined as the date of first dose to the date of death from non hematologic disease recurrence / progression | Baseline up to 96 weeks | 
| Failure Free Survival (FFS) | Defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy. | Baseline up to 12 months | 
| Changes in glucocorticoid dose | The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug. | Baseline up to 96 weeks | 
| Changes in symptom burden | Evaluate changes in symptom burden as measured by the Lee Symptom Scale. A change of 7 points on the Lee Symptom Scale will be considered clinically significant and relates to improvement in quality of life. | Baseline up to 96 weeks | 
| Maximum plasma concentration (Cmax) | Cmax is the maximum plasma concentration of TQ05105 or its metabolite(s). | Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 1; Pre-dose of day 3,day5, day 6 ;Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 7. | 
| Time to reach maximum plasma concentration (Tmax) | To characterize the pharmacokinetics of TQ05105 by assessment of time to reach maximum plasma concentration. | Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 1; Pre-dose of day 3,day5, day 6 ;Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 7. | 
| Area under the plasma concentration time curve (AUC0-t) | To characterize the pharmacokinetics of TQ05105 by assessment of area under the plasma concentration time curve from zero to infinity. | Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 1; Pre-dose of day 3,day5, day 6 ;Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 7. | 
| Incidence rate of adverse event | The occurrence rate of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs) assessed based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. | Baseline up to 96 weeks. |