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

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

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

Study Overview

• Status: Recruiting
• Conditions: Wiskott-Aldrich Syndrome
• Intervention / Treatment: Drug: Romiplostim; Drug: Eltrombopag

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: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna Shcherbina, MD, PhD; Phone Number: 6299 +7(495)2876570; Email: shcher26@hotmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117997
    • Recruiting
    • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
    • Contact: Anna Shcherbina, MD, PhD; Phone Number: 6299 +7(495)2876570; Email: shcher26@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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 Names: Nplate
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with overall platelet response (complete response + partial response) for romiplostim and eltrombopag group	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.	1 month (30 day +/- 7 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with bleeding events and severity of bleeding in romiplostim and eltrombopag group	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).	until discontinuation, from at least one month to one year
Number of participants with drug related adverse events in each treatment group	Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE).	until discontinuation, from at least one month to one year
Percentage of patients with overall platelet response (complete response + partial response) after switching from one TPO-RA to another one.		until discontinuation, from at least one month to one year

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): July 30, 2023

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: platelets; eltrombopag; romiplostim; thrombocytopenia
• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Disease; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Blood Platelet Disorders; Leukopenia; Leukocyte Disorders; Primary Immunodeficiency Diseases; Lymphopenia; Syndrome; Thrombocytopenia; Wiskott-Aldrich Syndrome
• Other Study ID Numbers: NCPHOI-2020-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No