A Study of TQ05105 Tablets in Subjects With Glucocorticoid-Refractory Acute Graft-Versus-Host Disease (aGVHD)

CTTQ

Status and phase: Completed; Phase 2; Phase 1

Conditions: Glucocorticoid-Refractory aGVHD

Treatments: Drug: TQ05105 tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT04941404

TQ05105-Ib-01

Details and patient eligibility

About

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

Enrollment: 13 patients

Sex: All

Ages: 12 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

TQ05105 tablets

Experimental group

Description:

Participants began oral administration of TQ05105 tablets at 10 mg twice daily (BID),followed by 5 mg or 15 mg BID depending on the situation of the study. twice daily in 28-day cycle until disease progression/intolerance occurs or the sponsor terminates the study.

Treatment:

Drug: TQ05105 tablets