Clinical trial NCT02760251: Immunomodulation With Romiplostim in Young Adults With ITP
Official title: Thrombopoietin-receptor Agonist-immunomodulation in Young Adult Primary Immune Thrombocytopenia (ITP): A Multi-center Open Label Trial With Romiplostim
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Immune Thrombocytopenia
Keywords: immunomodulation
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University Children's Hospital Basel
First posted: 2016-05-03
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Change in Interleukin (IL)-4 concentrations (pg/ml) from baseline to week 22
timeFrame: baseline and 22 weeks
Secondary outcomes:
measure: Change in immunomodulation as assessed by immune cell characteristics between baseline and week 22
timeFrame: baseline and 22 weeks
measure: Change in immunomodulation as assessed by immune cell characteristics between baseline and week 10
timeFrame: baseline and 10 weeks
measure: Change in immunomodulation as assessed by messenger ribonucleic acid (mRNA) of cytokines between baseline and week 22
timeFrame: baseline and 22 weeks
measure: Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 22
timeFrame: baseline and 22 weeks
measure: Change in immunomodulation as assessed by mRNA of cytokines between baseline and week 10
timeFrame: baseline and 10 weeks
measure: Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 10
timeFrame: baseline and 10 weeks
measure: Change in immunomodulation as assessed by cytokine concentrations between baseline and week 22
timeFrame: baseline and 22 weeks
measure: Change in immunomodulation as assessed by cytokine concentrations between baseline and week 10
timeFrame: baseline and 10 weeks
measure: Clinical response between baseline and week 52: number of severe bleeding
timeFrame: baseline and 52 weeks
measure: Clinical response between baseline and week 52: number of days in hospital
timeFrame: baseline and 52 weeks
measure: Clinical response between baseline and week 52: platelet more than >100G/l
timeFrame: baseline and 52 weeks
measure: Change in immunomodulation as assessed by immune cell characteristics between baseline and week 52
timeFrame: baseline and 52 weeks
measure: Change in immunomodulation as assessed by mRNA of immune cells between baseline and week 52
timeFrame: baseline and 52 weeks
measure: Change of immunomodulation as assessed by mRNA of cytokines between baseline and week 52
timeFrame: baseline and 52 weeks
measure: Change in immunomodulation as assessed by cytokine concentrations between baseline and week 52
timeFrame: baseline and 52 weeks
measure: Clinical response between baseline and week 52: frequency of use of rescue treatment
timeFrame: baseline and week 52
Other outcomes:
Locations:
city: Liestal
country: Switzerland
facility: Liestal Cantonal Hospital
state: Basel-Land
city: Lucerne
country: Switzerland
facility: Lucerne Cantonal Hospital
state: Lucern
city: Aarau
country: Switzerland
facility: Aarau Cantonal Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: University Hospital Bern
Study officials:
affiliation: UKBB
name: Thomas Kühne, Prof.Dr.med
role: PRINCIPAL_INVESTIGATOR
References: