SAT-242 - An Open-Label, Single Arm, Multicenter, Phase III Study on the Efficacy, Safety, and Pharmacokinetics of FP-001 42 Mg Controlled Release in Patients with Central (Gonadotropin Dependent) Precocious Puberty (Casppian Study)

Background
GnRHa are the only products approved for use in CPP and are considered the standard of care for this disorder. Optimal treatment inhibits the physical signs of pubertal progression, returns growth velocity to normal prepubertal rates, slows bone maturation, improves predicted adult height, and suppresses pubertal-hormonal-measures. FP-001 42 mg is a pre-mixed drug product containing 48 mg leuprolide mesylate (42 mg of free base) formulated to control and sustain the release of the bioactive leuprolide over a 6-month period after a single subcutaneous administration. The proposed product has been supplied as a single, sterile, pre-filled syringe that does not require pre-mixing prior to subcutaneous injection.
Results
The study's primary endpoint was defined as the percentage of patients with serum LH concentrations < 4 mIU/mL at 60 minutes following an abbreviated GnRHa stimulation test at Visit 5 (Week 24). The study successfully met its primary efficacy endpoint, with statistically significant results (P-value = 0.0005), demonstrating that 94% of patients had serum luteinizing hormone (LH) suppression to < 4 mIU/mL at 60 minutes following a GnRHa stimulation test at Week 24, and exceeded the pre-specified success criterion.
Percentage of Patients with Serum LH Concentration < 4 mIU/mL at Week 24 (ITT Population)

Summary of Patients with Response at Week 24 (ITT Population)
Variable/ Visit Status Overall
(N=94)
Patients with serum LH concentration < 4 mIU/mL
Visit 5 (Week 24) Responder 88 (93.62 %) Responder 88 (93.62 %)
Non-responder 6 (6.38 %) Non-responder 6 (6.38 %)
P-value 0.0005 P-value 0.0005
95% CI for responder (86.62, 97.62) 95% CI for responder (86.62, 97.62)

Methods
Primary Endpoint
• To determine the efficacy of subcutaneous FP-001 42 mg in suppressing GnRHa-stimulated LH to < 4 mIU/mL at 24 weeks for the treatment of children with Central Precocious Puberty (CPP). FP-001 42 mg will be considered effective for the treatment of children with CPP if ≥80% of patients exhibit LH suppression < 4 mIU/mL at Week 24.

Ky-Secondary Endpoints

• Safety and tolerability of FP-001 42 mg in children with CPP.
• Pharmacokinetics-PK-Pharmacodynamics-PD of FP-001 42 mg after the first administration. relationship of leuprolide serum concentrations to concentrations of serum-luteinizing-hormone-(LH), follicle-stimulating-hormone-(FSH), and to testosterone-estradiol.
• Change-in-height velocity, physical signs of puberty by Tanner-stages, and bone age progression at one year into treatment, namely 48 weeks post-first injection.
• Measure the ‘Acute-On-Chronic’-(AOC) phenomenon 48-hours after the second-dose of FP-001.

Conclusion
The Proportion of patients with serum luteinizing hormone (LH) suppression to < 4 mIU/mL at 60 minutes following a GnRHa stimulation test at Week 24 was 94%, and was statistically significant (P-value = 0.0005), offers new treatment option for CPP

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