Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Romiplostim Versus Eltrombopag in the Treatment of Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04371939
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Tracking Information
First Submitted Date  ICMJE April 29, 2020
First Posted Date  ICMJE May 1, 2020
Last Update Posted Date May 6, 2020
Actual Study Start Date  ICMJE November 5, 2019
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2020)
Percentage of patients with overall platelet response (complete response + partial response) for romiplostim and eltrombopag group [ Time Frame: 1 month (30 day +/- 7 days) ]
A complete response will be defined as a platelet count >100 x 109/L, partial - 30 x 109/L higher than the patient's pretreatment baseline count to 100 x 109/L.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2020)
  • Number of participants with bleeding events and severity of bleeding in romiplostim and eltrombopag group [ Time Frame: until discontinuation, from at least one month to one year ]
    The incidence and severity of bleeding events is evaluated with a modified World Health Organization (WHO) Bleeding Scale. (G1=Petechiae, epistaxis <30 min, G2=Mild blood loss, hematomas, epistaxis >30 min, melanotic stool G3=Gross blood loss, requiring blood transfusions, G4=Fatal bleeding).
  • Number of participants with drug related adverse events in each treatment group [ Time Frame: until discontinuation, from at least one month to one year ]
    Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE).
  • Percentage of patients with overall platelet response (complete response + partial response) after switching from one TPO-RA to another one. [ Time Frame: until discontinuation, from at least one month to one year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Romiplostim Versus Eltrombopag in the Treatment of Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome
Official Title  ICMJE Randomized, Two-arm Single-center Phase II Clinical Trial Comparing the Efficacy and Safety of Romiplostim Versus Eltrombopag in the Treatment of Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome
Brief Summary This is a prospective, open-label, randomized, two-arm clinical trial conducted to evaluate the safety and efficacy of romiplostim in comparison with eltrombopag in the treatment of thrombocytopenia in patients with Wiskott-Aldrich syndrome
Detailed Description

Wiskott-Aldrich syndrome (WAS) is a life-threatening primary immunodeficiency associated with bleeding of variable severity due to severe thrombocytopenia. Considering that the hemorrhagic events are a cause of death in 21% of WAS patients, management of thrombocytopenia constitutes a major challenge. Findings of defective platelet production by megakaryocytes and reduced in vitro pro-platelet formation suggested the possibility of megakaryocyte stimulation by TPO-RAs romiplostim, eltrombopag as a treatment strategy. Each of them has distinct pharmacodynamic, pharmacokinetic properties, different effects on megakaryopoiesis, and might have different efficacy in individual patients.

The aim of this study is to compare the efficacy and safety of romiplostim and another TPO-RA eltrombopag for the treatment of thrombocytopenia in patients with WAS and assess the benefit of switching these molecules in refractory subjects. The patients will be randomized in a 1:1 fashion to receive either romiplostim or eltrombopag.

After enrollment, (see detailed inclusion and exclusion criteria below) subjects under 18 years of age with a confirmed diagnosis of WAS and thrombocytopenia (platelet count of less than 70 x 109/L) will be assigned to receive romiplostim at an initial dose of 9 µg/kg subcutaneously per week or oral eltrombopag at a dose of 2-3mg/kg daily (ages 1 to 5 years) and 75 mg/daily (>6 years) for at least 1 month.

Bleeding severity will be evaluated with a modified World Health Organization (WHO) Bleeding Scale, lab tests (blood counts, biochemical analyses), ECG will be assessed after 30 days of treatment (30 +/- 7 days).

The efficacy of romiplostim/eltrombopag will be defined by the following criteria: complete response -an achievement of the platelet count >100 x 109/L, partial - platelet count at least 30 x 109/L higher than the patient's pretreatment baseline count up to to 100 x 109/L. No response will be defined as not achieving a platelet count of > 30 x 109/L from the baseline count.

Refractory patients will be switched to alternate TPO-RA agonist. Other reasons for switching that are not related to efficacy might include adverse events, active colitis, patient preference.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Wiskott-Aldrich Syndrome
Intervention  ICMJE
  • Drug: Romiplostim

    Participants will receive romiplostim at an initial dose of 9 µg/kg subcutaneously per week for at least 1 month depending on their response to study drug.

    Patients failing to achieve a complete platelet response cross over to arm II.

    Other Name: Nplate
  • Drug: Eltrombopag

    Participants will receive eltrombopag at a dose of 2-3mg/kg daily (ages 0 to 5 years) and 75 mg/daily (>6 years) for at least 1 month depending on their response to study drug.

    Patients failing to achieve a complete platelet response switch to arm I.

Study Arms  ICMJE
  • Experimental: I (Romiplostim)

    Participants will receive romiplostim at an initial dose of 9 µg/kg subcutaneously per week for at least 1 month depending on their response to study drug.

    Patients failing to achieve a complete platelet response cross over to arm II.

    Intervention: Drug: Romiplostim
  • Experimental: II (Eltrombopag)

    Participants will receive eltrombopag at a dose of 2-3mg/kg daily (ages 0 to 5 years) and 75 mg/daily (>6 years) for at least 1 month depending on their response to study drug.

    Patients failing to achieve a complete platelet response switch to arm I.

    Intervention: Drug: Eltrombopag
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 30, 2020)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Genetically verified Wiskott-Aldrich syndrome
  • Thrombocytopenia (platelet count < 70 x 109/L)
  • Age: under 18 years
  • Subject/legal representative has signed written informed consent.

Exclusion Criteria:

  • Patients, who do not meet the inclusion criteria.
  • Any prior history of arterial or venous thrombosis within the past year.
  • Arm II (eltrombopag):

    1. abnormal hepatic function -elevated AST/ALT > 1.5 times upper limit of normal within 4 weeks prior to enrollment
    2. Active colitis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anna Shcherbina, MD, PhD +7(495)2876570 ext 6299 shcher26@hotmail.com
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04371939
Other Study ID Numbers  ICMJE NCPHOI-2020-03
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Study Sponsor  ICMJE Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP