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

Chronic Graft Versus Host Disease Clinical Trial

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).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04944043
• Other study ID #: TQ05105-Ib/II-02
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 25, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• TQ05105 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.

Locations

Country	Name	City	State
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hanzhou	Zhejiang
China	The First Affiliated Hospital of USTC (Anhui Provincial Hospital)	Hefei	Anhui
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical College of HUST	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Recommended phase II dose (RP2D)	Recommended dose for phase II (Patients in phase Ib)	Baseline up to 4 weeks
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	Failure Free Survival (FFS)	Defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy.	Baseline up to 12 months
Secondary	Changes in glucocorticoid dose	The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug.	Baseline up to 96 weeks
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.