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Completed

NCT Number: NCT02760251

Immunomodulation With Romiplostim in Young Adults With ITP

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).

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Key information

Conditions

Immune Thrombocytopenia Autoimmune Diseases Blood Coagulation Disorders Blood Platelet Disorders Cytopenia Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhage Hemorrhagic Disorders Immune System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Purpura Purpura, Thrombocytopenic Purpura, Thrombocytopenic, Idiopathic Signs and Symptoms Skin Manifestations Thrombocytopenia Thrombotic Microangiopathies

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Liestal Cantonal Hospital, Liestal, Basel-Landschaft, Switzerland

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Romiplostim

Drug

Other names: Nplate

Primary outcomes

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

    Time frame: 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 outcomes

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: baseline and week 52

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Collaborators

  • University Children's Hospital Basel

Registry information

Official study title

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

Acronym: iROM

Important dates

Study start
2016
Primary completion
2019
Study completion
2020
First posted
May 3, 2016
Registry last updated
May 7, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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