Exploring the Efficacy, Safety of a Modified Starting Dosage of Avatrombopag in Immune Throbocytopenia (ITP) - a Pilot Study

Обзор

This is a single-center, open label pilot trial where patients with primary ITP who require second line treatment will be offered avatrombopag at a reduced starting dose, adjusted thereafter according to the response and continued for up to 24 weeks. The study aims to acquire experience on use of avatrombopag and explore the efficacy and safety of lower starting dose of avatrombopag

Подробное описание

Avatrombopag is an oral thrombopoietin receptor agonist that is licensed for chronic ITP. Avatrombopag is administered at a starting dose of 20 mg daily. Overshooting of platelet count is a frequent problem that occurs in 20 to 40% of the patients after initiating avatrombopag as recommended. In this open label, single arm, pilot study, we will start avatrombopag at a reduced starting dose of 20 mg every other day. The dose will be adjusted thereafter according to the platelet response. The study consists of 3 phases: Dose adjustment phase, a maintenance phase, and dose tapering/disconsolation and follow-up phase. The study aims to acquire experience on use of avatrombopag and explore the efficacy and safety of lower starting avatrombopag-dose, and assess the rate of sustained response off-treatment. The duration of treatment with avatrombopag is 6 months.

The study is an investigator-initiated trial sponsored by Center for Transplantation and Blood Diseases. Medical City Complex, Baghdad Iraq.

Вмешательства

• Препарат Avatrombopag 20 mg Oral Tablet
  Description: Patients will start on avatrombopag 20 mg every other day for a week then the dose will be readjusted according to the platelet count.

Первичные конечные точки

• Total Response Time [Срок оценки: 20 weeks]

Вторичные конечные точки (9)

• TTR [Срок оценки: 20 weeks]
• Response by day 8 [Срок оценки: 8 days]
• Rates of platelet overshoot. [Срок оценки: 6 weeks]
• Durable response rate. [Срок оценки: 20 weeks]
• The rates of treatment failure. [Срок оценки: 20 weeks]
• Bleeding complications during the study. [Срок оценки: 52 weeks]
• The safety of treatment with Avatrombopag. [Срок оценки: 52 weeks]
• The changes in HRQoL during the study. [Срок оценки: 20 weeks]
• The rates of Sustained Response Off-Treatment (SROT) at week 52. [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• Male or female aged ≥18 years.
• Diagnosis of primary ITP and having a platelet count of < 30 x109/L measured within two weeks prior to inclusion with failure to achieve response or relapse after at least one cycle of dexamethasone (20-40 mg daily for 4 days) or prednisone /prednisolone (1 mg/kg for at least two weeks). Shorter courses or lower doses are allowed if discontinued or modified due to side effects.
• Clinical need for second (subsequent) line treatment with a platelet elevating therapy assessed by the physician in charge.
• Signed and dated written informed consent.

Критерии исключения

• Previous treatment with TPO-RA.
• Pregnancy or lactation.
• Patients with active serious bleeding or at high risk of bleeding as judged by physician in charge.
• Females of child-bearing potential refusing to follow effective contraceptive methods (as described in SmPC) during treatment with Avatrombopag.
• Secondary ITP defined as ITP secondary to lymphoma or chronic lymphocytic leukemia; ITP secondary to the following autoimmune disorders Systemic Lupus Erythematosus or Antiphospholipid Syndrome; ITP secondary to Common Variable Immune Deficiency; ITP secondary to the following viral infections eg Human Immunodeficiency Virus.
• Concomitant autoimmune hemolytic anemia, Evans syndrome.
• Presence of any serious comorbidity where the condition may worsen the study drugs.
• Presence of active malignancy unless deemed cured by adequate treatment. Participants with the following neoplastic conditions can be included:

• Monoclonal gammopathy of undetermined significance (MGUS) or monoclonal B lymphocytosis of undetermined significance (MBUS)
• Basal/squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
• Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.

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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Ирак · 1 центр

• hematology center / Medical City — Baghdad

Публикации

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• Pascual-Izquierdo C, Sanchez-Gonzalez B, Canaro-Hirnyk MI, Garcia-Donas G, Menor-Gomez M, Gil-Fernandez JJ, Monsalvo-Saornil S, de-Laiglesia A, Alvarez-Roman MT, Jarque-Ramos I, Llacer MJ, Pedrote-Amador B, Zafra-Torres D, Caparros-Miranda I, Ortuzar-Pasalodos A, Revilla-Calvo N, Bastida JM, Chica-Gullon E, Alvarellos M, Jimenez-Barcenas R, Bernat S, Martinez-Carballeira D, Lakhwani S, Lopez-Ansoa PMID 39394928
• Virk ZM, Leaf RK, Kuter DJ, Goodarzi K, Connell NT, Connors JM, Al-Samkari H. Avatrombopag for adults with early versus chronic immune thrombocytopenia. Am J Hematol. 2024 Feb;99(2):155-162. doi: 10.1002/ajh.27080. Epub 2023 Dec 8. PMID 38063420
• Yamaguchi H, Iino M, Kowata S, Yamamoto R, Yamanouchi J, Imamura Y, Kirito K, Yokoyama K, Ito T, Ishikawa T, Shiratsuchi M, Tomiyama Y, Kamiya H, Zhang J, Jamieson BD. A phase 3 study of the efficacy and safety of avatrombopag in Japanese adults with chronic immune thrombocytopenia. Int J Hematol. 2025 Oct;122(4):521-532. doi: 10.1007/s12185-025-04001-4. Epub 2025 May 20. PMID 40392465
• Tarantino MD, Bussel JB, Lee EJ, Jamieson BD. A phase 3, randomized, double-blind, active-controlled trial evaluating efficacy and safety of avatrombopag versus eltrombopag in ITP. Br J Haematol. 2023 Aug;202(4):897-899. doi: 10.1111/bjh.18908. Epub 2023 Jun 20. No abstract available. PMID 37339869
• Mei H, Zhou H, Hou M, Sun J, Zhang L, Luo J, Jiang Z, Ye X, Xu Y, Lu J, Wang H, Hui A, Zhou Y, Hu Y. Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China. Res Pract Thromb Haemost. 2023 Jul 26;7(6):102158. doi: 10.1016/j.rpth.2023.102158. eCollection 2023 Aug. PMID 37700877
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• Matzdorff A, Alesci SR, Gebhart J, Holzhauer S, Hutter-Kronke ML, Kuhne T, Meyer O, Ostermann H, Pabinger I, Rummel M, Sachs UJ, Stauch T, Trautmann-Grill K, Wormann B. Expert Report on Immune Thrombocytopenia: Current Diagnostics and Treatment - Recommendations from an Expert Group from Austria, Germany, and Switzerland. Oncol Res Treat. 2023;46 Suppl 2:5-44. doi: 10.1159/000529662. Epub 2023 Feb PMID 36787705

Идентификаторы

NCT: NCT07133659 · RGHC007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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