Avatrombopag for the Treatment of Thrombocytopenia in Pediatric Subjects With Immune Thrombocytopenia for ≥6 Months

Subjects will be randomized in to blinded therapy of avatrombopag or placebo in a 3:1 ratio for a period of 12 weeks. Subjects who complete the 12 week treatment period and are eligible may continue to the open label extension phase which will last 2 years.

• Avatrombopag (Drug), also known as Doptelet: Oral avatrombopag tablet or sprinkle capsule
• Placebo (Drug): Placebo comparator tablet or sprinkle capsule

Primary outcomes

• Durable Platelet Response [Last 8 weeks of 12 week treatment regimen]: The proportion of subjects achieving at least 6 out of 8 weekly platelet counts ≥50×10\^9/L during the last 8 weeks of the 12 week Treatment Period in the Core Phase, in the absence of rescue medication
• Alternative Primary: Platelet Response [12 weeks of treatment]: The proportion of subjects for whom at least 2 consecutive platelet assessments are ≥50×10\^9/L over the 12 weeks of treatment in the Core Phase in the absence of rescue medication.

Secondary outcomes

• Percentage of Weeks Platelet Count ≥50×10^9/L [12 weeks of treatment]: The percentage of weeks subjects have a platelet count ≥50×10\^9/L during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy.
• Platelet Response at Day 8 [Day 8]: The proportion of subjects with a platelet count ≥50×10\^9/L at day 8, in the absence of rescue therapy.
• Percentage of Weeks Platelet Count Between ≥50×10^9/L and ≤150×10^9/L [12 weeks of treatment]: The percentage of weeks subjects have a platelet count between ≥50×10\^9/L and ≤150×10\^9/L, during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy.
• Rescue Medications [12 weeks of treatment]: The proportion of subjects who require rescue medications during 12 weeks of treatment in the Core Phase of the study.
• Incidence of Any Bleeding Event (WHO Grade 1-4) [12 weeks of treatment]: Overall incidence of bleeding events associated with ITP measured using the WHO Bleeding Scale (Grade 1-4).

Sex: All, ages: 1 Year to 17 Years

Inclusion Criteria:

* Male or female participants ≥1 and <18 years of age at Screening and Baseline with a diagnosis of primary ITP for ≥6 months duration and has had an insufficient response to a previous treatment, in the opinion of the Investigator.
* Participant has an average of 2 platelet counts <30×10\^9/L with no single count >35×10\^9/L in the screening period

Exclusion Criteria:

* Participants must not have a known history of secondary ITP, any history of arterial or venous thrombosis, including partial or complete thrombosis, known inherited thrombocytopenia, a history of myelodysplastic syndrome (MDS) or known history of congenital heart abnormalities or arrhythmias.

Participant flow

Outcome results

• Durable Platelet Response (Primary), Count of participants, Participants: Experimental: Avatrombopag 15; Placebo Comparator:Placebo 0 (p 0.0077)
• Alternative Primary: Platelet Response (Primary), Count of participants, Participants: Experimental: Avatrombopag 44; Placebo Comparator:Placebo 0 (p <0.0001)
• Percentage of Weeks Platelet Count ≥50×10^9/L (Secondary), Mean, percentage of weeks: Experimental: Avatrombopag 48.9 +/- 25.22; Placebo Comparator:Placebo 1.2 +/- 3.92 (p <0.0001)
• Platelet Response at Day 8 (Secondary), Count of participants, Participants: Experimental: Avatrombopag 30; Placebo Comparator:Placebo 0 (p <0.0001)
• Percentage of Weeks Platelet Count Between ≥50×10^9/L and ≤150×10^9/L (Secondary), Mean, percentage of weeks: Experimental: Avatrombopag 29.2 +/- 19.64; Placebo Comparator:Placebo 1.2 +/- 3.92 (p <0.0001)
• Rescue Medications (Secondary), Count of participants, Participants: Experimental: Avatrombopag 4; Placebo Comparator:Placebo 9 (p 0.0008)
• Incidence of Any Bleeding Event (WHO Grade 1-4) (Secondary), Count of participants, Participants: Experimental: Avatrombopag 45; Placebo Comparator:Placebo 19 (p 0.7175)

Adverse events

Time frame: Up to 12 weeks (Core Phase) and up to 2 years (Extension Phase)

Serious adverse events by term

Other adverse events by term

• Results publication: Leblebisatan, G. G., Aydinok, Y., Äcenal, Ş., Grainger, J., Grimes, A., Lambert, M., Zhang, J., Jamieson, B., Vredenburg, M., & Kolodny, S. (2025). PB0364: Evaluation of efficacy and safety of avatrombopag in children with ITP based on disease duration. RPTH, 9(Suppl 2).
• Results publication: Leblebisatan, G. G., Aydinok, Y., Ünal Cangül, Ş., Grainger, J., Grimes, A., Lambert, M., Zhang, J., Jamieson, B., Vredenburg, M., & Kolodny, S. (2025). PB0348: Consistent response to avatrombopag for pediatric ITP across various baseline characteristics. RPTH, 9(Suppl 2).
• Results publication: Grace, R. F., Leblebisatan, G., Aydinok, Y., Ünal Cangül, Ş., Grainger, J., Zhang, J., Alkhori Franzén, L., & Skuban, N. (2025). PS2234: Efficacy and safety of avatrombopag for the treatment of pediatric immune thrombocytopenia in the open-label extension of a Phase 3, randomized, double-blind, placebo-controlled trial. HemaSphere, 9(Suppl 1), 4067.
• Results publication: Scott Kolodny, Rachael Grace, Göksel Leblebisatan, Yesim Aydinok, Şule Ünal, John Grainger, Amanda Grimes, Michelle Lambert, Jessica Zhang, Brian Jamieson, Michael Vredenburg. Baseline Correlates With Durability of Avatrombopag Response in Pediatric Immune Thrombocytopenia. Pediatr Blood Cancer. 2025;72(Suppl S94):e31765. Abstract [# 304].
• Results publication: Scott Kolodny, Rachael Grace, Göksel Leblebisatan, YesimAydinok, Şule Ünal, John Grainger, Amanda Grimes, Michele Lambert, Jessica Zhang, Brian Jamieson, Michael Vredenburg. Clinically Meaningful Response to Avatrombopag for Treatment of Pediatric Immune Thrombocytopenia. Pediatr Blood Cancer. 2025;72(Suppl S06):e31765. Abstract [# 2011].
• Results publication: Grace RF, Leblebisatan G, Aydinok Y, Unal S, Grainger JD, Zhang J, Smallwood L, de Leon E, Jamieson BD; AVA-PED-301 Study Group. Avatrombopag for the treatment of children and adolescents with immune thrombocytopenia (AVA-PED-301): a multicentre, randomised, double-blind, placebo-controlled, phase 3b study. Lancet Haematol. 2025 Jul;12(7):e494-e504. doi: 10.1016/S2352-3026(25)00107-3. Epub 2025 May 23. PMID 40418942
• Results publication: Grace RF, Leblebisatan G, Aydinok Y, Unal S, Grainger JD, Zhang J, Smallwood L, de Leon E, Jamieson BD, DiRaimo J. Avatrombopag for treating children and adolescents with immune thrombocytopenia: a plain language summary. Expert Rev Hematol. 2026 Feb;19(2):107-116. doi: 10.1080/17474086.2025.2604524. Epub 2025 Dec 18. PMID 41411046

• Study Protocol (PDF, 2021-11-02)
• Statistical Analysis Plan (PDF, 2023-03-15)