Clinical trial NCT04944043: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Graft Versus Host Disease
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-29
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximal Tolerable Dose (MTD)
timeFrame: Baseline up to 4 weeks
measure: Recommended phase II dose (RP2D)
timeFrame: Baseline up to 4 weeks
measure: Best Overall Response Rate (BOR)
timeFrame: Baseline up to 96 weeks
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Baseline up to 52 weeks
measure: Duration of Response (DOR)
timeFrame: Baseline up to 96 weeks
measure: Overall survival (OS)
timeFrame: Baseline up to death event, up to 5 years.
measure: Non-relapse mortality (NRM)
timeFrame: Baseline up to 96 weeks
measure: Failure Free Survival (FFS)
timeFrame: Baseline up to 12 months
measure: Changes in glucocorticoid dose
timeFrame: Baseline up to 96 weeks
measure: Changes in symptom burden
timeFrame: Baseline up to 96 weeks
measure: Maximum plasma concentration (Cmax)
timeFrame: 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.
measure: Time to reach maximum plasma concentration (Tmax)
timeFrame: 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.
measure: Area under the plasma concentration time curve (AUC0-t)
timeFrame: 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.
measure: Incidence rate of adverse event
timeFrame: Baseline up to 96 weeks.
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
state: Anhui
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST
state: Hubei
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
state: Tianjin
city: Hanzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: