A Study (Phase 1b/2) of GenSci134 in Children With Idiopathic Short Stature (ISS)

A Phase Ib/II Multicenter, Randomized, Open-label, Active-controlled, Single/Multiple-dose, Dose-finding, Clinical Study of GenSci134 in Children With Idiopathic Short Stature

This study comprises two phases: Phase Ib and Phase II. Phase Ib is a multicenter, randomized, open-label, active-controlled, single-dose, dose-escalation study to evaluate the safety, tolerability, PK/PD profile, and immunogenicity of a single subcutaneous dose of GenSci134 in children with idiopathic short stature (ISS).

Phase II is a multicenter, randomized, open-label, active-controlled, multiple-dose, parallel-group study to assess the efficacy and safety of multiple subcutaneous doses of GenSci134 at different levels versus Norditropin® in children with ISS. It will also evaluate PK/PD profile, immunogenicity, and biomarkers to support dose selection for Phase III.

Inclusion Criteria:

• sInformed consent of parent or legal representative of participant and child assent, as age appropriate must be obtained before any study-related activities.
• At the time of signing the Informed consent form (ICF), the following conditions must be met:
• Phase Ib:

Girls: age ≥3 and ≤11 years, breast development at Tanner stage 1, body weight ≥16 kg; Boys: age ≥3 and ≤12 years, testis volume <4 mL, body weight ≥16 kg.

● Phase II: Girls: age ≥3 and ≤9 years, breast development at Tanner stage 1; Boys: age ≥3 and ≤10 years, testis volume <4 mL.

• Diagnosis of ISS at the time of ICF signing .
• BMI within the range of ±2 SD of the mean BMI for age and sex at screening（Phase II only）.
• No prior exposure to GH or IGF-1 therapy.
• Historical measurements of body height within 6-18 months prior to screening are available(Phase II only).
• BA-CA ≤ 1 year at screening(Phase II only).

Exclusion Criteria:

• Presence of any suspected or confirmed condition known to affect growth, including but not limited to:

  1. GHD.
  2. Turner Syndrome.
  3. Noonan syndrome.
  4. Laron Syndrome.
  5. Other genetic syndromes with short stature that are caused by chromosomal abnormalities or gene mutations, including but not limited to Prader-Willi syndrome, abnormal SHOX-1 gene analysis, or GH receptor deficiency.
  6. Born small for gestational age:
  7. Growth retardation due to malnutrition.
  8. Growth retardation due to hypothyroidism.
  9. Short stature with any other clearly identified etiology.

• Epiphyseal closure (Phase II only).

• Abnormal liver function, renal function, or coagulation profile.

• Current or prior history of any malignant disease; or a family history of malignancy.

• Presence of impaired glucose metabolism, or HbA1c ≥ 5.7%, or a confirmed diagnosis of diabetes mellitus.

• Clear medical history of cardiovascular, hepatic, renal, gastrointestinal, respiratory, hematological, neurological, or metabolic disorders, or any other condition that, in the opinion of the investigator, makes the participant unsuitable for participation in the study.

• Any clinically significant abnormality in vital signs, physical examinations, laboratory tests, 12-lead ECG, full spine anteroposterior and lateral X-ray, or B-mode ultrasound, other than those associated with the study disease, as judged by the investigator and will make the participant unsuitable for the study.

• A positive result for any of the following serological tests during the screening period: HBsAg, Anti-HCV, Anti-HIV, or TP-Ab.

• Known highly allergic diathesis or hypersensitivity to growth hormone products or any excipient of the investigational drug.

• Use within a specified period prior to screening or planned use during the study of medications that may interfere with growth hormone secretion or action, or other drugs known to affect growth and development.

• Participation in another clinical trial within 3 months prior to screening, or if the time since the last dose is less than 5 half-lives of the previous investigational drug at screening.

• Children have been treated with systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening (Phase II only).

• Children have been treated with inhaled budesonide or equivalent doses of inhaled glucocorticoids for more than 4 consecutive weeks within the last 12 months prior to screening (Phase II only).

• Receipt of any blood products within 3 months prior to the first dose, poor peripheral venous access, or any medical condition that will preclude tolerance of the blood sampling procedures.

• Administration of any vaccine within 14 days prior to the first dose or planned vaccination at any time during the study period.

• The participant and/or the parent/legal representative is likely to be non-compliant with respect to study conduct, as judged by the investigator.

• Any other condition that, in the opinion of the investigator, makes the participant unsuitable for participation in the study.