Back to results

Immunomodulation With Romiplostim in Young Adults With ITP (iROM)

Primary Purpose

Immune Thrombocytopenia

Status

Completed

Phase

Phase 4

Locations

Switzerland

Study Type

Interventional

Intervention

romiplostim

About this trial

This is an interventional treatment trial for Immune Thrombocytopenia focused on measuring immunomodulation

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Liestal Cantonal Hospital
Lucerne Cantonal Hospital
Aarau Cantonal Hospital
University Hospital Basel
University Hospital Bern

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Romiplostim

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in Interleukin (IL)-4 concentrations (pg/ml) from baseline to week 22

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

Change in immunomodulation as assessed by immune cell characteristics between baseline and week 22

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+

Change in immunomodulation as assessed by immune cell characteristics between baseline and week 10

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+

Change in immunomodulation as assessed by messenger ribonucleic acid (mRNA) of cytokines between baseline and week 22

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)

Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 22

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)

Change in immunomodulation as assessed by mRNA of cytokines between baseline and week 10

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)

Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 10

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)

Change in immunomodulation as assessed by cytokine concentrations between baseline and week 22

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

Change in immunomodulation as assessed by cytokine concentrations between baseline and week 10

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

Clinical response between baseline and week 52: number of severe bleeding

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

Clinical response between baseline and week 52: number of days in hospital

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

Clinical response between baseline and week 52: platelet more than >100G/l

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).

Change in immunomodulation as assessed by immune cell characteristics between baseline and week 52

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+

Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 52

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)

Change of immunomodulation as assessed by mRNA of cytokines between baseline and week 52

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)

Change in immunomodulation as assessed by cytokine concentrations between baseline and week 52

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

Clinical response between baseline and week 52: frequency of use of rescue treatment

Full Information

NCT ID

NCT02760251

First Posted

April 15, 2016

Last Updated

May 6, 2020

Sponsor

University Hospital, Basel, Switzerland

Collaborators

University Children's Hospital Basel

1. Study Identification

Unique Protocol Identification Number

NCT02760251

Brief Title

Immunomodulation With Romiplostim in Young Adults With ITP

Acronym

iROM

Official Title

Thrombopoietin-receptor Agonist-immunomodulation in Young Adult Primary Immune Thrombocytopenia (ITP): A Multi-center Open Label Trial With Romiplostim

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

April 2016 (undefined)

Primary Completion Date

July 2019 (Actual)

Study Completion Date

March 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Basel, Switzerland

Collaborators

University Children's Hospital Basel

4. Oversight

Data Monitoring Committee

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Immune Thrombocytopenia

Keywords

immunomodulation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Romiplostim

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

romiplostim

Other Intervention Name(s)

Nplate

Primary Outcome Measure Information:

Title

Change in Interleukin (IL)-4 concentrations (pg/ml) from baseline to week 22

Description

Time Frame

baseline and 22 weeks

Secondary Outcome Measure Information:

Title

Change in immunomodulation as assessed by immune cell characteristics between baseline and week 22

Description

Time Frame

baseline and 22 weeks

Title

Change in immunomodulation as assessed by immune cell characteristics between baseline and week 10

Description

Time Frame

baseline and 10 weeks

Title

Change in immunomodulation as assessed by messenger ribonucleic acid (mRNA) of cytokines between baseline and week 22

Description

Time Frame

baseline and 22 weeks

Title

Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 22

Description

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)

Time Frame

baseline and 22 weeks

Title

Change in immunomodulation as assessed by mRNA of cytokines between baseline and week 10

Description

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)

Time Frame

baseline and 10 weeks

Title

Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 10

Description

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)

Time Frame

baseline and 10 weeks

Title

Change in immunomodulation as assessed by cytokine concentrations between baseline and week 22

Description

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

Time Frame

baseline and 22 weeks

Title

Change in immunomodulation as assessed by cytokine concentrations between baseline and week 10

Description

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

Time Frame

baseline and 10 weeks

Title

Clinical response between baseline and week 52: number of severe bleeding

Description

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

Time Frame

baseline and 52 weeks

Title

Clinical response between baseline and week 52: number of days in hospital

Description

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

Time Frame

baseline and 52 weeks

Title

Clinical response between baseline and week 52: platelet more than >100G/l

Description

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).

Time Frame

baseline and 52 weeks

Title

Change in immunomodulation as assessed by immune cell characteristics between baseline and week 52

Description

Time Frame

baseline and 52 weeks

Title

Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 52

Description

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)

Time Frame

baseline and 52 weeks

Title

Change of immunomodulation as assessed by mRNA of cytokines between baseline and week 52

Description

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)

Time Frame

baseline and 52 weeks

Title

Change in immunomodulation as assessed by cytokine concentrations between baseline and week 52

Description

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

Time Frame

baseline and 52 weeks

Title

Clinical response between baseline and week 52: frequency of use of rescue treatment

Time Frame

baseline and week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Kühne, Prof.Dr.med

Organizational Affiliation

UKBB

Official's Role

Principal Investigator

Facility Information:

Facility Name

Liestal Cantonal Hospital

City

Liestal

State/Province

Basel-Land

Country

Switzerland

Facility Name

Lucerne Cantonal Hospital

City

Lucerne

State/Province

Lucern

Country

Switzerland

Facility Name

Aarau Cantonal Hospital

City

Aarau

Country

Switzerland

Facility Name

University Hospital Basel

City

Basel

ZIP/Postal Code

4000

Country

Switzerland

Facility Name

University Hospital Bern

City

Bern

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Immunomodulation With Romiplostim in Young Adults With ITP

We'll reach out to this number within 24 hrs