Background
Phase 3 double-blind placebo-controlled RCT (PETIT2). 62 children aged 1–17 years with ITP of ≥12 months duration (chronic ITP), platelet count ≤30×10⁹/L, and ≥1 prior ITP treatment. Randomized 2:1. First Phase 3 trial specifically designed and powered to evaluate a TPO receptor agonist in pediatric chronic ITP. Romiplostim (Nplate) SC weekly, weight-based dosing, for 24 weeks. Concomitant ITP therapies permitted with dose-stable criteria.
Interventions and follow up
Arm A: Romiplostim 1 mcg/kg SC weekly, titrated to 10 mcg/kg maximum to maintain platelet count 50–200×10⁹/L
Arm B: Placebo SC weekly
Primary endpoint: Durable platelet response (platelet ≥50×10⁹/L for ≥6 of the last 8 treatment weeks without rescue medication)
mFollow up: 24 week
Arm B: Placebo SC weekly
Primary endpoint: Durable platelet response (platelet ≥50×10⁹/L for ≥6 of the last 8 treatment weeks without rescue medication)
mFollow up: 24 week
Results
Durable platelet response: 52% (romiplostim) vs 10% (placebo), P=.0003
Platelet response weeks (median): 18/25 (romiplostim) vs 2/25 (placebo)
Overall response: 88% vs 32% had ≥1 platelet count ≥50×10⁹/L
Rescue therapy: 19% (romiplostim) vs 60% (placebo) required rescue
Platelet response weeks (median): 18/25 (romiplostim) vs 2/25 (placebo)
Overall response: 88% vs 32% had ≥1 platelet count ≥50×10⁹/L
Rescue therapy: 19% (romiplostim) vs 60% (placebo) required rescue
Adverse events
Main adverse events: Contusion 24% vs 20% (comparable). Epistaxis 24% vs 28%. Headache 14% vs 10%. Grade ≥3 AEs: 26% vs 39% (romiplostim vs placebo), driven by bleeding events in placebo. Neutralizing antibodies: none detected. Bone marrow reticulin: not assessed in 24-week study. No thromboembolic events. No deaths. Discontinuation due to AEs: 0% vs 0%.
Conclusions
Romiplostim achieved durable platelet responses in 52% of pediatric patients with chronic ITP versus 10% on placebo, with significant reduction in rescue therapy needs, establishing romiplostim as the first TPO-RA with Phase 3 evidence in pediatric chronic ITP.
Key Limitations
Key Limitations: Small sample size (n=62); powered for the primary endpoint but limited for secondary analyses and subgroup interpretation. 24-week duration. Inclusion of ages 1–17 years is a heterogeneous population (younger children may have different natural history). Long-term bone marrow monitoring for fibrosis in children requires separate studies. Spontaneous remission occurs in a portion of pediatric ITP patients, potentially confounding observed response; chronic ITP (≥12 months) minimizes but does not eliminate this.
Clinical Context
FDA approved August 2015 (Nplate) for children ≥1 year with chronic ITP following PETIT2 results. Eltrombopag was subsequently approved for pediatric ITP ≥1 year (PETIT/PETIT2-eltrombopag studies). Both TPO-RAs are now guideline-listed for pediatric chronic ITP. ASH 2019 ITP guidelines recommend TPO-RAs as standard second-line therapy in children as well as adults. The decision to use pharmacotherapy vs watchful waiting in pediatric ITP depends heavily on bleeding symptoms and quality of life rather than platelet count alone.
References