Back to resultsA Study of TQ05105 in Patients With Chronic Graft Versus Host Disease
Primary Purpose
Chronic Graft Versus Host Disease
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TQ05105 Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Graft Versus Host Disease
Eligibility Criteria
Inclusion Criteria:
1. Understood and signed an informed consent form. 2. ≥12 years old, Karnofsky Performance Scale of ≥60, life expectancy ≥ 6 months.
3. Has received allogeneic hematopoietic stem cell transplantation (alloSCT). 4. Clinically diagnosed moderate to severe cGVHD according to NIH Consensus Criteria.
5. Has received systemic or topical corticosteroids therapy and confirmed steroid-refractory/dependent cGVHD according to NIH Consensus Criteria.
6. 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:
1. 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.
3. Has uncontrollable active infections or infections requiring systematic treatment within 7 days before the first administration.
4. 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.
11. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.
Sites / Locations
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
- Zhujiang Hospital of Southern Medical University
- Nanfang Hospital of Southern Medical University
- Guangzhou First People's Hospital
- The First Affiliated Hospital of Guangxi Medical University
- The Second Hospital of Hebei Medical University
- The First Affiliated Hospital of Zhengzhou University
- Union Hospital Tongji Medical College Huazhong University of Science and Technology
- Tongji Hospital Tongji Medical College of HUST
- The First Affiliated Hospital of Soochow University
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- The First Affiliated Hospital, Zhejiang University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TQ05105 Tablet
Arm Description
TQ05105 tablet 10mg given orally, twice daily in 28-cycle.
Outcomes
Primary Outcome Measures
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)
Recommended phase II dose (RP2D)
Recommended dose for phase II (Patients in phase Ib)
Best Overall Response Rate (BOR)
Percentage of participants achieving complete response (CR) and partial response (PR). (Patients in phase II)
Secondary Outcome Measures
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.
Duration of Response (DOR)
DOR defined as time from earliest date of disease response to earliest date of disease progression.
Overall survival (OS)
OS defined as the time from randomization to the time of death from any cause.
Non-relapse mortality (NRM)
Defined as the date of first dose to the date of death from non hematologic disease recurrence / progression
Failure Free Survival (FFS)
Defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy.
Changes in glucocorticoid dose
The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug.
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.
Maximum plasma concentration (Cmax)
Cmax is the maximum plasma concentration of TQ05105 or its metabolite(s).
Time to reach maximum plasma concentration (Tmax)
To characterize the pharmacokinetics of TQ05105 by assessment of time to reach maximum plasma concentration.
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.
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.
Full Information
NCT ID
NCT04944043
First Posted
June 21, 2021
Last Updated
July 24, 2023
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04944043
Brief Title
A Study of TQ05105 in Patients With Chronic Graft Versus Host Disease
Official Title
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).
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 25, 2021 (Actual)
Primary Completion Date
June 30, 2023 (Actual)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Graft Versus Host Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TQ05105 Tablet
Arm Type
Experimental
Arm Description
TQ05105 tablet 10mg given orally, twice daily in 28-cycle.
Intervention Type
Drug
Intervention Name(s)
TQ05105 Tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximal Tolerable Dose (MTD)
Description
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)
Time Frame
Baseline up to 4 weeks
Title
Recommended phase II dose (RP2D)
Description
Recommended dose for phase II (Patients in phase Ib)
Time Frame
Baseline up to 4 weeks
Title
Best Overall Response Rate (BOR)
Description
Percentage of participants achieving complete response (CR) and partial response (PR). (Patients in phase II)
Time Frame
Baseline up to 96 weeks
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Percentage of participants achieving complete response (CR) and partial response (PR) during the study according to the cGVHD NIH Consensus Criteria.
Time Frame
Baseline up to 52 weeks
Title
Duration of Response (DOR)
Description
DOR defined as time from earliest date of disease response to earliest date of disease progression.
Time Frame
Baseline up to 96 weeks
Title
Overall survival (OS)
Description
OS defined as the time from randomization to the time of death from any cause.
Time Frame
Baseline up to death event, up to 5 years.
Title
Non-relapse mortality (NRM)
Description
Defined as the date of first dose to the date of death from non hematologic disease recurrence / progression
Time Frame
Baseline up to 96 weeks
Title
Failure Free Survival (FFS)
Description
Defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy.
Time Frame
Baseline up to 12 months
Title
Changes in glucocorticoid dose
Description
The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug.
Time Frame
Baseline up to 96 weeks
Title
Changes in symptom burden
Description
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.
Time Frame
Baseline up to 96 weeks
Title
Maximum plasma concentration (Cmax)
Description
Cmax is the maximum plasma concentration of TQ05105 or its metabolite(s).
Time Frame
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.
Title
Time to reach maximum plasma concentration (Tmax)
Description
To characterize the pharmacokinetics of TQ05105 by assessment of time to reach maximum plasma concentration.
Time Frame
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.
Title
Area under the plasma concentration time curve (AUC0-t)
Description
To characterize the pharmacokinetics of TQ05105 by assessment of area under the plasma concentration time curve from zero to infinity.
Time Frame
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.
Title
Incidence rate of adverse event
Description
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.
Time Frame
Baseline up to 96 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230001
Country
China
Facility Name
Zhujiang Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510280
Country
China
Facility Name
Nanfang Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Facility Name
Guangzhou First People's Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
511457
Country
China
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Facility Name
The Second Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450052
Country
China
Facility Name
Union Hospital Tongji Medical College Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Facility Name
Tongji Hospital Tongji Medical College of HUST
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
The First Affiliated Hospital, Zhejiang University School of Medicine
City
Hanzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
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A Study of TQ05105 in Patients With Chronic Graft Versus Host Disease
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