A Multicenter Randomized Non‑Inferiority Trial of Weekly Somatrogon versus Daily Somatropin in Pediatric Patients with Small‑for‑Gestational‑Age or Idiopathic Short Stature

The primary objective is to assess whether weekly somatrogon demonstrates non‑inferior efficacy compared with daily somatropin (GENOTROPIN) in treatment‑naïve pediatric patients diagnosed with small for gestational age or idiopathic short stature, thereby establishing comparable growth outcomes.

The trial enrolled 150 participants diagnosed with Small for gestational age (SGA) or idiopathic short stature (ISS). Eligible children were pre‑pubertal, Tanner stage 1, with females aged ≥4 years (EU) or ≥3 years (non‑EU) and <9 years, and males aged ≥4 years (EU) or ≥3 years (non‑EU) and <11 years at the time of consent. Bone age had to be ≤ chronological age (and for ISS not more than 2 years below chronological age) as documented within the preceding eight weeks. Both sexes were included. Participants were required to be capable of providing signed informed consent/assent and to meet the specific growth‑parameter thresholds defining SGA (birth weight/length <‑2 SDS) or ISS (height <‑2 SDS with peak GH >10 ng/mL). The population comprised generally healthy children without evidence of growth hormone deficiency.

The multicenter, phase III, interventional study evaluates the non‑inferiority of weekly somatrogon compared with daily Genotropin in pediatric participants diagnosed with small for gestational age or idiopathic short stature. Eligible children are screened for eligibility, providing informed consent/assent, and then allocated to either the test arm (Ngenla 60 mg solution for injection) or the comparator arm (GENOTROPIN 12 mg powder for injection). The trial consists of a screening visit, a baseline visit initiating treatment, scheduled follow‑up visits throughout a 12‑month treatment period to assess growth parameters and safety, and a final end‑of‑study visit at month 12. Primary efficacy is measured by the annualized height velocity after 12 months of therapy. Participants remain in the study for approximately one year, with the possibility of earlier discontinuation for reasons such as withdrawal of consent, occurrence of a serious adverse event, or failure to comply with protocol‑defined procedures. Recruitment is planned to commence on 1 April 2026 and conclude by 30 January 2028.

The investigational product is somatrogon supplied as Ngenla 60 mg solution for injection in a pre‑filled pen. It is a sterile solution intended for subcutaneous administration. The prescribed dose is 60 mg per injection, administered once weekly throughout the treatment period. Dosing is performed by the participant or caregiver using the pre‑filled pen, and adherence is monitored by electronic pen memory readouts and patient‑maintained injection logs.

The comparator is somatropin provided as GENOTROPIN 12 mg powder for solution for injection. After reconstitution, the product is administered as a sterile solution for subcutaneous injection on a daily basis. The daily dose is 12 mg, prepared according to the manufacturer’s instructions. Compliance with the daily regimen is assessed through diary entries and periodic count of used vials.

Efficacy will be evaluated by the primary endpoint of annualized height velocity assessed after 12 months of treatment. The height velocity will be calculated based on stature measurements obtained at baseline and at the 12‑month visit, providing an annualized growth rate for each participant.