TQ05105 Tablets (Rovadicitinib Tablets): TQ05105 is an inhibitor of Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), and Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and 2 (ROCK2).
Study summary
This is an open-label, single-arm, multi-center phase II study consisting of two cohorts. Cohort 1 evaluates the pharmacokinetics (PK) of TQ05105 in myelofibrosis participants with normal, mild, or moderate renal impairment to guide dosing. Cohort 2 evaluates the efficacy and safety of TQ05105 in participants with intermediate/high-risk myelofibrosis who are refractory, relapsed, or intolerant to prior Janus kinase (JAK) inhibitor therapy.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Voluntary and signed informed consent, good compliance.
2. Age ≥18 years (at time of signing informed consent); Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2; life expectancy ≥24 weeks.
3. Diagnosis of primary myelofibrosis (PMF) per World Health Organization (WHO) 2016, or post-polycythemia vera myelofibrosis (post-PV-MF) or post-essential thrombocythemia myelofibrosis (post-ET-MF) per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria; Janus kinase 2 (JAK2) mutation status not restricted.
4. Intermediate or high risk per Dynamic International Prognostic Scoring System (DIPSS).
5. Cohort 1: Renal function classified as normal, mild impairment, or moderate impairment. Cohort 2: Prior Janus kinase (JAK) inhibitor therapy with refractory, relapsed, or intolerant.
6. Spleen enlargement (except Cohort 1).
7. Peripheral blood and bone marrow blasts ≤10%.
8. No growth factors, colony-stimulating factors, thrombopoietin, or platelet transfusion within 2 weeks before first dose; and routine blood parameters meet requirements within 7 days before first dose.
9. Adequate major organ function within 7 days before first dose per protocol (renal function not restricted for Cohort 1).
10. Agreement to use effective contraception during the study and for 6 months after; negative pregnancy test for females of childbearing potential; non-lactating.
Exclusion Criteria:
1. Prior allogeneic stem cell transplantation, or autologous stem cell transplantation within 3 months before first dose, or planned stem cell transplantation.
2. Prior treatment with 2 or more Janus kinase (JAK) inhibitors (except Cohort 1).
3. Prior splenectomy or splenic radiotherapy within 6 months before first dose.
4. Other malignancies within 3 years before first dose or currently present (exceptions per protocol).
5. Factors affecting oral drug absorption.
6. Non-hematologic toxicity from prior therapy not recovered to ≤ grade 1 (excluding hypertension and alopecia).
7. Major surgery or significant traumatic injury within 4 weeks before first dose.
8. Congenital bleeding or coagulation disorders.
9. Arterial/venous thrombosis event within 6 months before first dose.
10. History of substance abuse or mental disorder.
11. Active or uncontrolled severe infection.
12. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
13. Grade ≥2 myocardial ischemia or infarction, arrhythmia, QT prolongation, or grade ≥2 congestive heart failure.
14. Uncontrolled hypertension despite standard therapy.
15. Renal failure requiring hemodialysis or peritoneal dialysis.
16. Newly diagnosed pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before first dose.
17. History of immunodeficiency or organ transplantation.
18. Epilepsy requiring treatment.
19. Use of protocol-prohibited myelofibrosis (MF) medications, immunomodulators, or immunosuppressants within specified time before first dose.
20. Use of Chinese patent medicines with anti-tumor indications approved by National Medical Products Administration (NMPA) within 2 weeks before first dose.
21. Uncontrolled pleural effusion, pericardial effusion, or ascites.
22. Live attenuated vaccine within 4 weeks before first dose or planned during the study.
23. Known hypersensitivity to study drug or excipients.
24. Diagnosis of active autoimmune disease within 2 years before first dose.
25. Participation in another interventional clinical trial with investigational drug within 4 weeks before first dose.
26. Any condition that, in the investigator's judgment, seriously endangers subject safety or interferes with study completion.
Primary outcome measure(s)
Proportion of subjects with ≥35% reduction in spleen volume from baseline at week 24 (SVR35) — up to 24 weeks SVR35 at week 24 as assessed by Independent Review Committee (IRC)
Peak concentration (Cmax) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Maximum plasma concentration of TQ05105 and its metabolite(s).
Time to peak concentration (Tmax) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Time to reach maximum plasma concentration of TQ05105 and its metabolite(s).
Elimination half-life (t1/2) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Half-life of TQ05105 and its metabolite(s) in plasma.
Area under the curve from time 0 to last measurable concentration (AUC0-t) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) AUC from time 0 to the last measurable concentration of TQ05105 and its metabolite(s).
Area under the curve from time 0 to infinity (AUC0-∞) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) AUC from time 0 extrapolated to infinity for TQ05105 and its metabolite(s).
Total clearance (CLt) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Total body clearance of TQ05105 and its metabolite(s) from plasma.
Renal clearance (CLr) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Renal clearance of TQ05105 and its metabolite(s).
Apparent volume of distribution (Vd/F) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Apparent volume of distribution of TQ05105 and its metabolite(s) after oral administration.
Elimination rate constant (λz) — Pre-dose on Cycle 1 Day 1 and Day 7; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 1; and 15, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 7. (28 days a cycle) Terminal elimination rate constant of TQ05105 and its metabolite(s).
Trial sites (24)
Facility
City
Region
Status
The First Affiliated Hospital of University of Science and Technology of China
Hefei
Anhui
Recruiting
Fujian Medical University Union Hospital
Fuzhou
Fujian
Recruiting
Guangzhou First Municipal People's Hospital
Guangzhou
Guangdong
Recruiting
The First Affiliated Hospital of Guangxi Medical University
Nanning
Guangxi
Recruiting
Cangzhou People's Hospital rovince
Cangzhou
Hebei
Recruiting
Affiliated Hospital of Chengde Medical College
Chengde
Hebei
Recruiting
The Second Hospital of Hebei Medical University
Shijiazhuang
Hebei
Recruiting
Xingtai People's Hospital
Xingtai
Hebei
Recruiting
Henan Cancer Hospital
Zhengzhou
Henan
Recruiting
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
Wuhan
Hubei
Recruiting
Union Hospital Tongji College Huazhong University of Science and Technology
Wuhan
Hubei
Recruiting
Zhuzhou Central Hospital
Zhuzhou
Hunan
Recruiting
Nanjing Drum Tower Hospital
Nanjin
Jiangsu
Recruiting
Jiangsu Provincial Hospital of Traditional Chinese Medicine
Nanjing
Jiangsu
Recruiting
The First Hospital of Jilin University
Changchun
Jilin
Recruiting
Shengjing Hospital Affiliated to China Medical University
Shenyang
Liaoning
Recruiting
The First Affiliated Hospital of Air Force Medical University
Xi'an
Shaanxi
Recruiting
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an
Shaanxi
Recruiting
Shanghai Sixth People's Hospital
Shanghai
Shanghai Municipality
Recruiting
Heping Hospital Affiliated To Changzhi Medical College
Changzhi
Shanxi
Recruiting
Sichuan Provincial People's Hospital
Chengdu
Sichuan
Recruiting
Chinese Academy of Medical Sciences Hematology Hospital
Tianjin
Tianjin Municipality
Recruiting
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi
Xinjiang
Recruiting
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou
Zhejiang
Recruiting
More Chia Tai Tianqing Pharmaceutical Group Co., Ltd. trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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