A Study of Switching Avatrombopag and Rh-TPO in ITP

Corticosteroid-resistant or Relapsed ITP Clinical Trial

Official title:

A Prospective Observational Study of Switching Avatrombopag and Rh-TPO in Chinese Adult Patients With Primary Immune Thrombocytopenia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04913597
• Other study ID #: ITP-SWITCH1
• Status: Not yet recruiting
• Start date: June 20, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2021
• Source: Peking University People's Hospital
• Contact: Haixia Fu, MD
• Phone: 8610-88324577
• Email: fuhaixia_210[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Thrombopoietin receptor agonists (TPO-RAs) represent a highly effective and well-tolerated second-line ITP treatment that provides excellent responses.If there is cross-resistance between 2 drugs for the treatment of adult ITP is still unkonwn.The purpose of this study is to investigate the efficacy and safety of switching avatrombopag and rh-TPO in adults with ITP.

Description:

Thrombopoietin Receptor Agonists (TPO-RAs) are novel treatments for patients with chronic Primary Immune Thrombocytopenia (ITP). According to the findings of mechanism-based studies, rhTPO competes with endogenous TPO for binding to TPO-R while avatrombopag has an additive effect with endogenous TPO, indicating that the treatment mechanism and side-effect profiles could be somewhat different between these drugs. If there is cross-resistance between 2 drugs for the treatment of adult ITP is still no answer. The purpose of this study is to investigate the efficacy and safety of switching avatrombopag and rh-TPO in adults with ITP.This is a non-interventional study. Patients who fail previous steroids and receive rh-TPO and then switch to avatrombopag or vice versa will be enrolled. The reason for switch will be recorded. The efficacy, safety, and patient/physician preference will be assessed and compared between the two agents.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1.18 years or older 2.Primary ITP 3.Failed initial glucocorticosteroid treatment, 4.Applying rhTPO or Eltrombopag as subsequent treatment 5.Switch from rh-TPO to eltrombopag or vice versa 6.Normal neutrophils 7.Available follow-up at least 6 weeks after switching

Exclusion Criteria:

1. HIV positive status, or active infection of HBV or HCV

2. Suffering from a serious or progressive disease, which, in the investigator's judgment, put the subject at undue risk for participation in this study (i.e. cancer or pre-cancer, immunocompromised, uncontrolled diabetes, epilepsy, severe cardio-cerebrovascular disease(s) (i.e. stroke, idiopathic aortic stenosis, aneurysm, hypertrophic obstructive cardiomyopathy, ischaemic heart disease, tachyarrhythmias, severe heart failure [classified as NYHA III-IV], severe lung dysfunctions, etc))

3. History of thrombosis plus two or more risk factors as defined in Caprini thrombosis risk assessment model

4. Lactating or pregnant women, or WOCBP who are unwilling to use highly effective contraceptive measures during the study period

5. Abnormal liver and renal functions: AST or ALT or total bilirubin =1.5 × ULN, and/or creatinine =176.8 µmol/L

6. Women of childbearing potential (WOCBP) that are pregnant or wish to become pregnant during the prospective phase of the study.

7. Other conditions which the investigator considers inappropriate for enrollment

Related Conditions & MeSH terms

• Corticosteroid-resistant or Relapsed ITP

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

References & Publications (6)

Bussel JB. Avatrombopag. Br J Haematol. 2018 Nov;183(3):342-343. doi: 10.1111/bjh.15568. Epub 2018 Oct 23. — View Citation

Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3. Review. — View Citation

Liu XG, Bai XC, Chen FP, Cheng YF, Dai KS, Fang MY, Feng JM, Gong YP, Guo T, Guo XH, Han Y, Hong LJ, Hu Y, Hua BL, Huang RB, Li Y, Peng J, Shu MM, Sun J, Sun PY, Sun YQ, Wang CS, Wang SJ, Wang XM, Wu CM, Wu WM, Yan ZY, Yang FE, Yang LH, Yang RC, Yang TH, Ye X, Zhang GS, Zhang L, Zheng CC, Zhou H, Zhou M, Zhou RF, Zhou ZP, Zhu HL, Zhu TN, Hou M. Chinese guidelines for treatment of adult primary immune thrombocytopenia. Int J Hematol. 2018 Jun;107(6):615-623. doi: 10.1007/s12185-018-2445-z. Epub 2018 Apr 4. Review. — View Citation

Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, Cuker A, Despotovic JM, George JN, Grace RF, Kühne T, Kuter DJ, Lim W, McCrae KR, Pruitt B, Shimanek H, Vesely SK. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866. doi: 10.1182/bloodadvances.2019000966. Erratum in: Blood Adv. 2020 Jan 28;4(2):252. — View Citation

Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, Ghanima W, Godeau B, González-López TJ, Grainger J, Hou M, Kruse C, McDonald V, Michel M, Newland AC, Pavord S, Rodeghiero F, Scully M, Tomiyama Y, Wong RS, Zaja F, Kuter DJ. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019 Nov 26;3(22):3780-3817. doi: 10.1182/bloodadvances.2019000812. — View Citation

Wörmann B. Clinical indications for thrombopoietin and thrombopoietin-receptor agonists. Transfus Med Hemother. 2013 Oct;40(5):319-25. doi: 10.1159/000355006. Epub 2013 Sep 11. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Initial response after switching	Rate of response at 4 weeks after switching from rhTPO to avatrombopag or vise versa	4 weeks
Secondary	Response rate at 12 weeks after switching	Rate of response at 12 weeks after switching from rhTPO to avatrombopag or vise versa	12 weeks
Secondary	Initial response after switching according to the reasons of switching	Rate of response at 1 month after switching according to the reasons of switching,such as lack of efficacy, Platelet count fluctuations, development of adverse events,patient's or doctor's preference	4 weeks
Secondary	Rate of response at 12 weeks after switching according to the reasons of switching	Rate of response at 12 weeks after switching according to the reasons of switching,such as lack of efficacy, Platelet count fluctuations, development of adverse events,patient's or doctor's preference	12 weeks
Secondary	Time to response	Time to CR or R from switching	4 weeks
Secondary	Durable response	The maintenance of platelet count = 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 24 weeks follow-up.	24 weeks
Secondary	Incidence of bleeding events	Incidence of clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale	24 weeks
Secondary	Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)	In all participants ,use ITP-PAQ to assess the Health Related Quality of Life(HRQoL) before and after treatment.	24 weeks
Secondary	Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)	In all participants ,use FACIT-F to assess the Health Related Quality of Life(HRQoL) before and after treatment.	24 weeks
Secondary	Safety assessment	Number of Participants with side effects of the drugs	24 weeks