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

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

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

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.

Inclusion Criteria:

1. Male or female aged ≥18 years.
2. 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.
3. Clinical need for second (subsequent) line treatment with a platelet elevating therapy assessed by the physician in charge.
4. Signed and dated written informed consent.

Exclusion Criteria:

1. Previous treatment with TPO-RA.

2. Pregnancy or lactation.

3. Patients with active serious bleeding or at high risk of bleeding as judged by physician in charge.

4. Females of child-bearing potential refusing to follow effective contraceptive methods (as described in SmPC) during treatment with Avatrombopag.

5. 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.

6. Concomitant autoimmune hemolytic anemia, Evans syndrome.

7. Presence of any serious comorbidity where the condition may worsen the study drugs.

8. 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)

9. 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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