A Study of Switching Avatrombopag and Rh-TPO in ITP

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Corticosteroid-resistant or Relapsed ITP

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Haixia Fu, MD; Phone Number: 8610-88324577; Email: fuhaixia_210@163.com
• Study Contact Backup: Name: Yun He, MD; Phone Number: 18910504949; Email: heyun04@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

adult ITP patients

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Recombinant human thrombopoietin (rh-TPO) group; Patients who fail previous steroids and avatrombopag and then switch to Rh-TPO will be enrolled. The reason for switch will be recorded. Patients will be given rh-TPO 300 U/kg once daily for 14 days as initial treatment. After initial treatment, maintenance therapy were performance. At initial therapy, rhTPO will be suspended when platelet counts ≥100×10^9 / L. During maintenance therapy, patients with platelet counts >150×10^9 / L will suspend treatment until platelet counts drop to ≤150×10^9 / L. Dosing interval will be prolonged when platelet count is ≥100×10^9 / L to ≤150×10^9 / L. Dose modification is not required when platelet count is ≥30×10^9 / L to <100×10^9 / L. The efficacy, safety, and patient/physician preference will be assessed.
Avatrombopag group; Patients who fail previous steroids and rh-TPO and then switch to avatrombopag will be enrolled. The reason for switch will be recorded. Patients will be given avatrombopag 20mg once daily as initiate treatment, and adjust the dosage according to the count of platelets. The maximum dose of avatrombopag is 40mg daily.Avatrombopag will be terminated any time the platelet counts increased above 250×10^9/L. Dose adjustment of avatrombopag will be allowed to maintain platelet counts between 30×10^9/L and 150×10^9/L. The efficacy, safety, and patient/physician preference will be assessed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial response after switching	Rate of response at 4 weeks after switching from rhTPO to avatrombopag or vise versa	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate at 12 weeks after switching	Rate of response at 12 weeks after switching from rhTPO to avatrombopag or vise versa	12 weeks
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
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
Time to response	Time to CR or R from switching	4 weeks
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
Incidence of bleeding events	Incidence of clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale	24 weeks
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
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
Safety assessment	Number of Participants with side effects of the drugs	24 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Haixia Fu, MD, Peking University People's Hospital

Publications and helpful links

General Publications

• 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.
• Wormann 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.
• Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, Cuker A, Despotovic JM, George JN, Grace RF, Kuhne 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.
• 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.
• Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, Ghanima W, Godeau B, Gonzalez-Lopez 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.
• Bussel JB. Avatrombopag. Br J Haematol. 2018 Nov;183(3):342-343. doi: 10.1111/bjh.15568. Epub 2018 Oct 23. No abstract available.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 20, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: May 29, 2021
• First Submitted That Met QC Criteria: May 29, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 4, 2021
• Last Update Submitted That Met QC Criteria: May 29, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Immune Thrombocytopenia; Recombinant human thrombopoietin; switching; avatrombopag
• Other Study ID Numbers: ITP-SWITCH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No