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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат GenSci134 Injection
  only one dose of GenSci134 to be given, subcutaneous , 6 dose levels will be assigned.
• Препарат Recombinant Human Growth Hormone Injection(Norditropin® FlexPro®)
  multiple doses of Norditropin® FlexPro® quaque die (QD) for 28 consecutive days by subcutaneous injections.

Первичные конечные точки

• Phase Ib: Incidence of Treatment Emergent Adverse Events （TEAEs） [Срок оценки: From Day 1 to Day 35]
• Phase II: Annualized height velocity (AHV) at Week 24 of treatment [Срок оценки: 24 weeks]

Вторичные конечные точки (12)

• Phase Ib: Areas under the drug concentration-time curve (AUC0-t, AUC0-∞) of GenSci134 [Срок оценки: From Day 1 to Day 29]
• Phase Ib: Time to maximum concentration (Tmax) of GenSci134 [Срок оценки: From Day 1 to Day 29]
• Phase Ib: Maximum concentration (Cmax) of GenSci134 [Срок оценки: From Day 1 to Day 29]
• Phase Ib: Half-life (t1/2) of GenSci134 [Срок оценки: From Day 1 to Day 29]
• Phase Ib: Serum level of IGF-1and IGFBP-3 and their changes from baseline. [Срок оценки: rom Day 1 to Day 29]
• Phase Ib: Incidence and timing of positive anti-drug antibody (ADA) and/or neutralizing antibody (NAb) (if applicable) [Срок оценки: From Day 1 to Day 29]
• Phase II: Change from baseline in HT SDS at each visit [Срок оценки: From baseline to Week 24 of the treatment period]
• Phase II: Change from baseline in AHV at each visit [Срок оценки: From baseline to Week 24 of the treatment period]
• Phase II: Change from baseline in BA/CA at each visit [Срок оценки: From baseline to Week 24 of the treatment period]
• Phase II: Incidence of TEAEs [Срок оценки: From the first dose to the end of the trial]
• Phase II: Serum concentration of GenSci134. [Срок оценки: From baseline to Week 24 of the treatment period]
• Phase II: Serum level of IGF-1and IGFBP-3 and their changes from baseline. [Срок оценки: From baseline to Week 24 of the treatment period]

Критерии участия

Критерии включения

• 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).

Критерии исключения

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

• GHD.
• Turner Syndrome.
• Noonan syndrome.
• Laron Syndrome.
• 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.
• Born small for gestational age:
• Growth retardation due to malnutrition.
• Growth retardation due to hypothyroidism.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology — Ухань

Идентификаторы

NCT: NCT07450053 · GenSci134-203

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗