Phase III, open-labeled, randomized and multicenter clinical trial to evaluate the superiority of romiplostim plus dexamethasone vs dexamethasone alone in patients with newly diagnosed primary immune thrombocytopenia

The main objective of the study is to evaluate the superiority of romiplostim plus dexamethasone versus dexamethasone alone in the treatment of primary immune thrombocytopenia, with sustained response to any ITP treatment and without World Health Organization grade 2 or higher bleeding, after six months from cessation of treatment.

Maximum time on treatment with romiplostim will be 12 months (365 days). Then, patients will be followed up for 6 additional months (180 days) after stopping romiplostim.

Clinical rules are included if romiplostim dose should be modified or finished. In case of dexamethasone, no dose adjustment is permitted.

The evaluation of romiplastim plus dexamethasone´s superiority in different periods and platelet count, proportion of patients with complete response (CR), global response (GR), early response (ER) and initial response (IR); time to loss of response (LoR), adverse events, quality of life and healthcare resources use are included as secondary objectives.

Main inclusion criteria:

1. Age ≥ 18 years of age at the time of signing informed consent.
2. Newly diagnosis of primary ITP according to the International Working Group assessment [1] and previously untreated for ITP.
3. Platelet counts <30x109/L or ITP with platelet counts <50x109/L and concomitant bleeding symptoms.
4. Serum creatinine concentration ≤1.5 mg/dL.

Main exclusion criteria:

1. World Health Organization's performance status >2.
2. Previous therapy with rituximab (within 3 months previous of study enrollment), corticosteroids or, therapy with other immunomodulating agents within 1 month before of enrolment;,prior use of hematopoietic analogs and or fostamatinib for any other reason despite ITP three months before enrolment.
3. Previous use of romiplostim, polyethylene glycol-recombinant human megakaryocyte growth and development factor, Eltrombopag, recombinant human anti-thrombopoietin, or any platelet-producing agent three months before enrolment.
4. Alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study.
5. Splenectomy within 3 months of the screening visit or planned splenectomy during study period.
6. Abnormal renal function (serum creatinine > 1.5 mg/dL).
7. Active hepatic disease (evidenced by alanine aminotransferase [ALT] or aspartate aminotransferase [AST] levels >5 times the upper limit of normal (it will only be necessary to determine one of the two transaminases
8. Severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio >1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
9. Patients with known immunoglobulin M seropositive tests for cytomegalovirus and/or Epstein-Barr virus in the previous month.
10. Patients with an active viral infection at screening with: Hepatitis B Virus, Hepatitis C Virus, detectable virus charge of HIV.
11. Intolerance to dexamethasone.
12. History of a bone marrow stem cell disorder.
13. Active or prior malignancy except adequately treated (ie, complete surgical excision with negative margins) basal cell carcinoma.
14. History of helicobacter pylori by urea breath test or stool antigen test within 6 months of enrollment, if available.
15. History of myelodysplastic syndrome, systemic lupus erythematosus, or autoimmune cytopenia.
16. History of antiphospholipid antibody syndrome.
17. History of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura.
18. History of deep or superficial venous thromboembolism in the last 12 months or stroke, acute ischaemic heart disease or acute peripheral vascular disease in the last 6 months.
19. Hypersensitivity to any recombinant Escherichia coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune) or known sensitivity to any of the products to be administered during dosing
20. Currently enrolled in another investigational device or drug study or < 30 days since ending another investigational device or drug studies, or receiving other investigational agents.
21. Will have any other investigational procedures performed while enrolled in this clinical study.
22. Pregnant or breastfeeding, or planning to become pregnant or breastfeed during treatment or within 1 month after the end of treatment.
23. Female subject of childbearing potential is not willing to use, in combination with her partner, an acceptable method of effective contraception during treatment and for 1 month after the end of treatment. Females of childbearing potential should only be included after a negative, pregnancy test.
24. Will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge.
25. Any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
26. Other serious comorbidities at investigator criteria.

The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.

Along the study

Direct collaborators within the study