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Immunomodulation With Romiplostim in Young Adults With ITP (iROM)

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ClinicalTrials.gov Identifier: NCT02760251
Recruitment Status : Recruiting
First Posted : May 3, 2016
Last Update Posted : November 5, 2018
Sponsor:
Collaborator:
University Children's Hospital Basel
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
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 : April 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2020


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 Name: Nplate




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02760251


Contacts
Contact: Alexandra Schifferli, Dr.med 0041617041212 alexandra.schifferli@ukbb.ch

Locations
Switzerland
Liestal Cantonal Hospital Recruiting
Liestal, Basel-Land, Switzerland
Contact: Geneviève Favre, Dr.med         
Lucerne Cantonal Hospital Recruiting
Lucerne, Lucern, Switzerland
Contact: Axel Rüfer, Dr. med         
Aarau Cantonal Hospital Recruiting
Aarau, Switzerland
Contact: Nathan Cantoni, Dr. med         
University Hospital Basel Recruiting
Basel, Switzerland, 4000
Contact: Jakob Passweg, Prof.Dr.med.         
University Hospital Bern Not yet recruiting
Bern, Switzerland
Contact: Alicia Rovo, Dr.med         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
University Children's Hospital Basel
Investigators
Principal Investigator: Thomas Kühne, Prof.Dr.med UKBB

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02760251     History of Changes
Other Study ID Numbers: 20149180
First Posted: May 3, 2016    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital, Basel, Switzerland:
immunomodulation

Additional relevant MeSH terms:
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms