Chronic Graft Versus Host Disease
Conditions
Brief summary
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.
Interventions
DRUGTQ05105 Tablet
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.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase II dose (RP2D) | Baseline up to 4 weeks | Recommended dose for phase II (Patients in phase Ib) |
| Maximal Tolerable Dose (MTD) | Baseline up to 4 weeks | 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) |
| Best Overall Response Rate (BOR) | Baseline up to 96 weeks | Percentage of participants achieving complete response (CR) and partial response (PR). (Patients in phase II) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-relapse mortality (NRM) | Baseline up to 96 weeks | Defined as the date of first dose to the date of death from non hematologic disease recurrence / progression |
| Failure Free Survival (FFS) | Baseline up to 12 months | Defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy. |
| Changes in glucocorticoid dose | Baseline up to 96 weeks | The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug. |
| Changes in symptom burden | Baseline up to 96 weeks | 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. |
| Overall Response Rate (ORR) | Baseline up to 52 weeks | Percentage of participants achieving complete response (CR) and partial response (PR) during the study according to the cGVHD NIH Consensus Criteria. |
| Time to reach maximum plasma concentration (Tmax) | 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. | To characterize the pharmacokinetics of TQ05105 by assessment of time to reach maximum plasma concentration. |
| Area under the plasma concentration time curve (AUC0-t) | 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. | To characterize the pharmacokinetics of TQ05105 by assessment of area under the plasma concentration time curve from zero to infinity. |
| Incidence rate of adverse event | Baseline up to 96 weeks. | 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. |
| Maximum plasma concentration (Cmax) | 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. | Cmax is the maximum plasma concentration of TQ05105 or its metabolite(s). |
| Duration of Response (DOR) | Baseline up to 96 weeks | DOR defined as time from earliest date of disease response to earliest date of disease progression. |
| Overall survival (OS) | Baseline up to death event, up to 5 years. | OS defined as the time from randomization to the time of death from any cause. |
Countries
China
Outcome results
None listed