Clinical trial NCT04941404: A Study of TQ05105 Tablets in Subjects With Glucocorticoid-Refractory Acute Graft-Versus-Host Disease (aGVHD)
Official title: A Single Arm, Open-label, Multicenter, Phase Ib Study of TQ05105 Tablets in Subjects With aGVHD
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glucocorticoid-Refractory aGVHD
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-28
Enrollment: 13
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label,single arm,Phase Ib study,in order to evaluate the safety,tolerability, preliminary efficacy and pharmacokinetics of TQ05105 tablets in subjects with Glucocorticoid-Refractory aGVHD


Eligibility criteria: Inclusion Criteria:

1. Subjects voluntarily participated in the study and signed an informed consent, with good compliance.
2. Aged 12-75, gender is not limited.
3. Subjects who has received allogeneic hematopoietic stem cell transplantation (allo-HSCT) previously.
4. Clinically suspected grades II to IV acute GVHD as per MAGIC guidelines.
5. Drug resistance after glucocorticoid treatment.
6. Absolute neutrophils count (ANC) \>1×109/L,Platelet(PLT)≥20×109/L within 48 hours before initial treatment.
7. Male or female subjects should agree use an adequate method of contraception during the study and within 6 months after the end of the study (such as intrauterine devices , contraceptives or condoms) ;No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the first administration.

Exclusion Criteria:

1. Subjects with a history of progressive multifocal leukoencephalopathy.
2. Subjects with many factors influencing oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.).
3. Arteriovenous thrombotic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, etc..
4. Severe respiratory diseases (requiring mechanical ventilation or O2 saturation \< 90%), active tuberculosis, pulmonary hypertension and pulmonary embolism, etc..
5. Subjects with a history of psychotropic drug abuse and can not quit or have mental disorders.
6. Subjects with any severe and/or uncontrolled disease, including:

(1) Unsatisfactory blood pressure control with more than 2 drugs (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥ 100mmHg) ; (2) Patients with grade ≥2 myocardial ischemia or infarction, arrhythmias (including QTc≥480ms), and grade ≥2 congestive heart failure (New York Heart Association classification); (3) Uncontrolled active infections including bacteria, fungi, parasites or viruses such ascytomegalovirus, Epstein-Barr virus, and human herpes virus 6; (4) Cirrhosis, active hepatitis; (5) Human immunodeficiency virus(HIV) positive, active syphilis; (6) Creatinine clearance rate \< 30 mL/min,calculated by Cockcroft Gault formula; (7) Patients with epilepsy and need treatment. 7. Subjects with evidence of recurrence of primary disease or relapsed after allo-HSCT treatment.

8. There were grade 2 or higher toxicity (except aGVHD) caused by previous allo HSCT treatment.

9. Subjects who received allo-HSCT more than once in the past. 10. Subjects who received more than one kind of systemic treatment for Glucocorticoid-Refractory aGVHD.

11. The clinical manifestations were new-onset chronic GVHD or overlapping GVHD syndrome with both acute and chronic GVHD features.

12. Allergic to the investigational drug or its ingredients. 13. Subjects who used Janus kinase inhibitor (JAK) therapy after receiving Allo-HSCT.

14. Subjects who participated in other clinical trials within 4 weeks before initial administration.

15. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are considered unsuitable for other reasons.

Primary outcomes:
measure: Drug tolerance of the first cycle (Stage 1)
timeFrame: Day 28 after initial administration
measure: Objective Response Rate (ORR) at Day 28 (Stage 2)
timeFrame: Day 28 after initial administration
Secondary outcomes:
measure: CR Rate at Day 28
timeFrame: Day 28 after initial administration
measure: ORR at Day 28 and Day 56
timeFrame: Day 28 and Day 56 after initial administration
measure: Duration of Response (DOR)
timeFrame: From initial administration to day 30 after the last administration
measure: Cumulative dose of glucocorticoid at Day 56
timeFrame: Day 56 after initial administration
measure: Event Free Survival (EFS）
timeFrame: From initial administration to Day 30 day after the last administration
measure: Overall Survival (OS)
timeFrame: From initial administration to day 30 days after the last administration
measure: Incidence of Malignancy Relapse/Progression(MR),Non-Relapse Mortality(NRM)
timeFrame: From initial administration to 30 days after the last administration
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From initial administration to day 30 after the last administration
measure: Tmax
timeFrame: 7 days after initial administration
measure: Cmax
timeFrame: 7 days after initial administration
measure: AUC0-t
timeFrame: 7 days after initial administration
Other outcomes:
Locations:
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Tianjing
country: China
facility: Hematology Hospital of the chinese Academy of Medical Sciences
state: Tianjing
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: