iROM: Immunomodulation With Romiplostim in Young Adults With ITP

• Sponsor: University Hospital, Basel, Switzerland (Other)
• Overall Status: Completed
• CT.gov ID: NCT02760251
• Collaborator: University Children's Hospital Basel (Other)
• Enrollment: 15
• Locations: 5
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study aims to investigate immunomodulatory effects of thrombopoietin-receptor Agonist (TPO-RA) in patients with primary ITP, who failed first-line therapy or who became intolerant to it. It is hypothesized that the early phase of this autoimmune disease may exhibit a stronger immunomodulatory potential in response to a stimulus, such as romiplostim. Such a process may subsequently be capable to induce regulatory mechanisms or tolerance.

Romiplostim (a thrombopoietin-receptor agonist, TPO-RA) will be administered subcutaneously once weekly over 22 weeks with a starting dose of 1mcg/kg body weight. The dose will be adjusted based on platelet counts as described in the summary of Product Characteristics (SmPC).

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenia	Drug: romiplostim	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Thrombopoietin-receptor Agonist-immunomodulation in Young Adult Primary Immune Thrombocytopenia (ITP): A Multi-center Open Label Trial With Romiplostim
• Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Romiplostim Romiplostim (a thrombopoietin-receptor agonist, TPO-RA) will be administered subcutaneously once weekly over 22 weeks with a starting dose of 1mcg/kg body weight. The dose will be adjusted based on platelet counts as described in the summary of Product Characteristics (SmPC). Followup examination at week 52.	Drug: romiplostim; Other Names: Nplate

Outcome Measures

Primary Outcome Measures

1. Change in Interleukin (IL)-4 concentrations (pg/ml) from baseline to week 22 [baseline and 22 weeks]

   The primary aim of the study is to demonstrate an immunomodulatory effect of the study drug. Investigators expect a shift in the Th1/Th2 balance towards Th2. The primary outcome is to compare the pre- and post-treatment IL-4 concentrations (pg/ml) of all included patients (Th2 profile). Assessment of change in pre- and post-treatment IL-4 concentrations (pg/ml).

Secondary Outcome Measures

1. Change in immunomodulation as assessed by immune cell characteristics between baseline and week 22 [baseline and 22 weeks]

   Immunologic parameters will be investigated between baseline and week 22 of the study: immune cell characteristics fluorescence-activated cell sorting (FACS): B cells: cluster of Differentiation Antigen (CD)3- cluster of Differentiation Antigen (CD)19+ Memory B lymphocytes CD19+cluster of Differentiation Antigen (CD)10-cluster of Differentiation Antigen (CD)27+cluster of Differentiation Antigen (CD)38- Plasma cells: CD19+ CD10- cluster of Differentiation Antigen (CD)20- CD27++ cluster of Differentiation Antigen (CD)38++ Tcells and subpopulations: CD3+/ CD3+ CD4+/ CD3+ cluster of Differentiation Antigen (CD)8+ natural killer (NK) cells CD3- cluster of Differentiation Antigen (CD)16+ cluster of Differentiation (CD)56+ Monocytes CD56- cluster of Differentiation Antigen (CD)14 (low) CD16+ cluster of Differentiation Antigen (CD)33 Tregs CD4+ cluster of Differentiation Antigen (CD)25 superhigh FoxP3+

2. Change in immunomodulation as assessed by immune cell characteristics between baseline and week 10 [baseline and 10 weeks]

   Immunologic parameters will be investigated between baseline and week 10 of the study: immune cell characteristics FACS: B cells: CD3- CD19+ Memory B lymphocytes CD19+CD10-CD27+CD38- Plasma cells: CD19+ CD10- CD20- CD27++ CD38++ Tcells and subpopulations: CD3+/ CD3+ CD4+/ CD3+ CD8+ NK cells CD3- CD16+ CD56+ Monocytes CD56- CD14 (low) CD16+ CD33 Tregs CD4+ CD25 superhigh FoxP3+

3. Change in immunomodulation as assessed by messenger ribonucleic acid (mRNA) of cytokines between baseline and week 22 [baseline and 22 weeks]

   mRNA of cytokines will be investigated between baseline and week 22 mRNA essays (real-time quantitative PCR): cytokine mRNA (interleucin (IL)2, interleucin (IL)4, interleucin (IL)6, interleucin (IL)10, IL17, interleucin (IL)35, IFNgamma, TNFalpha, transforming growth factor (TGF)-β)

4. Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 22 [baseline and 22 weeks]

   mRNA of immune cells will be investigated between baseline and week 22 mRNA essays (real-time quantitative PCR): mRNA Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt), Tregs (Foxp3)

5. Change in immunomodulation as assessed by mRNA of cytokines between baseline and week 10 [baseline and 10 weeks]

   mRNA of cytokines will be investigated between baseline and week 10 mRNA essays (real-time quantitative PCR): cytokine mRNA (IL2, IL4, IL6, IL10, IL17, IL35, IFNgamma, TNFalpha, TGF-β)

6. Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 10 [baseline and 10 weeks]

   mRNA of immune cells will be investigated between baseline and week 10 mRNA essays (real-time quantitative PCR): mRNA Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt), Tregs (Foxp3)

7. Change in immunomodulation as assessed by cytokine concentrations between baseline and week 22 [baseline and 22 weeks]

   cytokine concentration will be investigated between baseline and week 22 ELISA Cytokines: IL2, IL4, IL6, IL10, IL17, IL35, IFNgamma, TNFalpha, TGF- β

8. Change in immunomodulation as assessed by cytokine concentrations between baseline and week 10 [baseline and 10 weeks]

   cytokine concentration will be investigated between baseline and week 10 ELISA Cytokines: IL2, IL4, IL6, IL10, IL17, IL35, IFNgamma, TNFalpha, TGF- β

9. Clinical response between baseline and week 52: number of severe bleeding [baseline and 52 weeks]

   Clinical characterization of response to romiplostim therapy will be assessed additionally : measurement of severe bleeding (score Bolton-Maggs)

10. Clinical response between baseline and week 52: number of days in hospital [baseline and 52 weeks]

    Clinical characterization of response to romiplostim therapy will be assessed additionally : need of inpatient daycare

11. Clinical response between baseline and week 52: platelet more than >100G/l [baseline and 52 weeks]

    Clinical characterization of response to romiplostim therapy will be assessed additionally : assessment of platelet response to romiplostim, according to the definitions of Rodeghiero et al. (49).

12. Change in immunomodulation as assessed by immune cell characteristics between baseline and week 52 [baseline and 52 weeks]

    Immunologic parameters will be investigated between baseline and week 52 of the study: immune cell characteristics FACS: B cells: CD3- CD19+ Memory B lymphocytes CD19+CD10-CD27+CD38- Plasma cells: CD19+ CD10- CD20- CD27++ CD38++ Tcells and subpopulations: CD3+/ CD3+ CD4+/ CD3+ CD8+ NK cells CD3- CD16+ CD56+ Monocytes CD56- CD14 (low) CD16+ CD33 Tregs CD4+ CD25 superhigh FoxP3+

13. Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 52 [baseline and 52 weeks]

    mRNA of immune cells will be investigated between baseline and week 52 mRNA essays (real-time quantitative PCR): mRNA Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt), Tregs (Foxp3)

14. Change of immunomodulation as assessed by mRNA of cytokines between baseline and week 52 [baseline and 52 weeks]

    mRNA of cytokines will be investigated between baseline and week 52 mRNA essays (real-time quantitative PCR): cytokine mRNA (IL2, IL4, IL6, IL10, IL17, IL35, IFNgamma, TNFalpha, TGF-β)

15. Change in immunomodulation as assessed by cytokine concentrations between baseline and week 52 [baseline and 52 weeks]

    cytokine concentration will be investigated between baseline and week 52 ELISA Cytokines: IL2, IL4, IL6, IL10, IL17, IL35, IFNgamma, TNFalpha, TGF- β

16. Clinical response between baseline and week 52: frequency of use of rescue treatment [baseline and week 52]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent as documented by signature (see informed consent form)

• Primary ITP according to the definition of Rodeghiero et al. (52) and a platelet count of <30x109/l

• Age range: 18-45 years

• Previously treated patients, with failure or intolerance to first-line therapy, or relapse after first-line therapy, i.e. corticosteroids, intravenous immunoglobulin (IVIG), or anti-D immunoglobulins

Exclusion Criteria:

• Adults older than 45 and children younger than 18 years

• Platelet count higher than 30x109/l at time of screening

• Suspicion of secondary ITP

• Positive family history for ITP

• Presence or history of autoimmune disease as judged by the investigator

• Hepatosplenomegaly

• Presence or history of relevant hepatic disease as judged by the investigator

• Presence or history of thromboembolic disease as judged by the investigator

• Patients with splenectomy

• Women who are pregnant or breast feeding

• Intention to become pregnant during the course of the study

• Lack of safe double contraception (see 7.1)

• Any vaccination 2 weeks prior start of the study

• Drugs with a known impact on the immune system or on platelet function must be recorded and an exclusion of the study should be discussed with the study center

• Known or suspected non-compliance, drug or alcohol abuse

• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia of the study subject

• Participation in another study with investigational drug within the 30 days preceding and during the present study

• Previous enrolment into the current study

• Previous treatment with romiplostim or eltrombopag

• Hypersensitivity to the active substance or to any of the excipients or to E. coli derived proteins

• Enrolment of the investigator, his/her family members, employees and other dependent persons

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liestal Cantonal Hospital	Liestal	Basel-Land	Switzerland
2	Lucerne Cantonal Hospital	Lucerne	Lucern	Switzerland
3	Aarau Cantonal Hospital	Aarau		Switzerland
4	University Hospital Basel	Basel		Switzerland	4000
5	University Hospital Bern	Bern		Switzerland

Sponsors and Collaborators

• University Hospital, Basel, Switzerland
• University Children's Hospital Basel

Investigators

• Principal Investigator: Thomas Kühne, Prof.Dr.med, UKBB

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT02760251
• Other Study ID Numbers: 20149180
• First Posted: May 3, 2016
• Last Update Posted: May 7, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University Hospital, Basel, Switzerland: immunomodulation
• Additional relevant MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic

Study Results

No Results Posted as of May 7, 2020