A Study of TQ05105 in Patients With Chronic Graft Versus Host Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TQ05105 Tablet TQ05105 tablet 10mg given orally, twice daily in 28-cycle. |
Drug: TQ05105 Tablet
TQ05105 tablet is a JAK inhibitor, which can inhibit the abnormal activation of JAK2-V617F mutation, thereby inhibiting the sustained abnormal activation of JAK / STAT pathway.
|
Outcome Measures
Primary Outcome Measures
- Drug tolerance of the first cycle [Baseline up to 4 weeks]
Dose-limiting toxicity events related to the investigational drug occured within 28 days after initial administration.
- Overall Response Rate (ORR) [Baseline up to 24 weeks]
Percentage of participants achieving complete response (CR) and partial response (PR).
Secondary Outcome Measures
- Best 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.
- Duration of Response (DOR) [Baseline up to 52 weeks]
DOR defined as time from earliest date of disease response to earliest date of disease progression.
- Overall survival（OS） [Baseline up to 52 weeks]
OS defined as the time from first dose to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
- Non-relapse mortality（NRM） [Baseline up to 52 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 52 weeks]
The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug.
- Changes in symptom burden [Baseline up to 52 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.
- 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 metabolite(s)
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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- Understood and signed an informed consent form. 2. ≥12 years old, Karnofsky Performance Scale of ≥60, life expectancy ≥ 6 months.
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Has received allogeneic hematopoietic stem cell transplantation (alloSCT). 4. Clinically diagnosed moderate to severe cGVHD according to NIH Consensus Criteria.
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Has received systemic or topical corticosteroids therapy and confirmed steroid-refractory/dependent cGVHD according to NIH Consensus Criteria.
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Has received at least 1 lines of therapy for cGVHD. 7. Adequate laboratory indicators. 8. No pregnant or breastfeeding women, and a negative pregnancy test.
Exclusion Criteria:
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- Has active acute GVHD. 2. Has previously failed to respond to JAK inhibitors for GVHD, or who had used JAK inhibitors within 4 weeks before the first administration.
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Has uncontrollable active infections or infections requiring systematic treatment within 7 days before the first administration.
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Development of other basic diseases. 5. Has malignant tumors within 3 years. 6. Has multiple factors affecting oral medication. 7. Has substance abuse or a psychotic disorder. 8. Has severe and / or uncontrolled disease. 9. Allergic to drugs or its constituents. 10. Has participated in any other clinical trials within 4 weeks before first administration.
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According to the judgement of the investigators, there are other factors that may lead to the termination of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital, Zhejiang University School of Medicine | Hanzhou | Zhejiang | China | 310000 |
Sponsors and Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TQ05105-Ⅰb/Ⅱ-02