A Study of ABSK061 to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy in Children With Achondroplasia

Up to 50 children aged 6 to \< 12 years (inclusive of 6 years) with ACH and up to 30 children aged 3 to \< 6 years (inclusive of 3 years) with ACH are expected to be enrolled in the dose escalation part of the study; up to 30 children aged 3 to \< 12 years (inclusive of 3 years) with ACH are expected to be enrolled in the RDE confirmation part.

Children enrolled in this study will be required to complete at least 6 months and up to 2 years of growth assessment and observation of natural history of ACH in the sponsor's observational study (ABSK061-001).

Dose Escalation Part All patients enrolled in the dose escalation part will continue to receive ABSK061 once daily (QD) dosing frequency and will enter the extended treatment period for 52 weeks after completing 26 weeks of treatment.

The dose escalation includes a total of 5 potential dose levels starting at an initial dose of 0.064 mg/kg QD. In the absence of DLTs or ≥ grade 2 drug-related adverse events, the initial maximum permitted dose increment will not exceed 200%. In the presence of a DLT or ≥ grade 2 drug-related adverse event, dose escalation for subsequent cohorts will follow a modified Fibonacci scheme, in which the first two consecutive dose cohorts will each receive a maximum dose increase of up to 67% and 50%, respectively, and the remaining dose cohorts will receive a maximum of 33% increase. The potential dose levels to be explored are listed in the table below. Based on cumulative safety, PK/PD, efficacy data, other potential dose levels not listed may also be explored in this study following the dose escalation rules.

Dose escalation part will be divided into Part A and Part B according to patient age, with Part A enrolling children with ACH aged 6 to \< 12 years (inclusive of 6 years) and Part B enrolling children with ACH aged 3 to \< 6 years (inclusive of 3 years). In this study, two sentinel patients will be set for both parts of each dose level, thereby the interval for the first dose between the first 2 patients and the third patient is not less than 28 days.

RDE Confirmation Part In this part, up to 30 children aged 3 to \< 12 years (inclusive of age 3) with ACH will be enrolled to receive one or two RDEs. The RDEs will be selected from the safe doses determined in the dose escalation to further evaluate the safety and efficacy of ABSK061 in children with ACH. Patients in this part will not be included in the DLT evaluable population. Dose decisions for RDE Confirmation Part will be based on discussion and alignment between the sponsor and investigators. Safety, PK/PD, and efficacy data will be monitored and assessed in real time during the study. The study may be discontinued early if any safety risk to the patients are identified, upon agreement between the investigators and sponsor.