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

NCT ID: NCT04371939

Last Updated: 2020-05-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-05
• Study Completion Date: 2023-07-30

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.

Conditions

Wiskott-Aldrich Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Romiplostim

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

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.

Interventions

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 Type: 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.

Intervention Type: DRUG

Other Intervention Names

Nplate

Eligibility Criteria

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.

• 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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Anna Shcherbina, MD, PhD

Role: CONTACT

shcher26@hotmail.com

+7(495)2876570 ext. 6299

Facility Contacts

Anna Shcherbina, MD, PhD

Role: primary

shcher26@hotmail.com

+7(495)2876570 ext. 6299

Other Identifiers

NCPHOI-2020-03

Identifier Type: -

Identifier Source: org_study_id