A Study of GenSci134 in Children With Growth Hormone Deficiency (PGHD)

Официальное название

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

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 to assess safety, tolerability, PK/PD profile, and immunogenicity of GenSci134 in children with GHD. 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 GHD. It will also evaluate PK/PD profile and immunogenicity 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: Treatment Emergent Adverse Events （TEAEs） [Срок оценки: From the first dose 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-1 and IGFBP-3 and their changes from baseline. [Срок оценки: From 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 28 of the extension period]
• Phase II: Change from baseline in AHV at each visit [Срок оценки: From baseline to Week 28 of the extension period]
• Phase II: Change from baseline in BA/CA at each visit. [Срок оценки: From baseline to Week 28 of the extension period]
• Phase II: Treatment Emergent Adverse Events（TEAEs） [Срок оценки: From the first dose to Week 29 of the extension period]
• Phase II: Serum concentration of GenSci134. [Срок оценки: From baseline to Week 28 of the extension period]
• Phase II: Serum level of IGF-1and IGFBP-3 and their changes from baseline. [Срок оценки: From baseline to Week 28 of the extension period]

Критерии участия

Критерии включения

• Informed 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 ≥3and ≤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.

• BMI within the range of ±2 SD of the mean BMI for age and sex at screening
• Height is at least 2 SD below the mean HT for age and sex (HT SDS ≤ -2.0) at screening according to the normal pediatric population standards
• Diagnosis of GHD confirmed by two different GH stimulation tests performed at screening or within 12 months prior to screening.
• No prior exposure to GH or IGF-1therapy.
• Absence of intracranial tumor, as confirmed by MRI or CT. Images or scans obtained within 1 year prior to screening can be used as screening data if accompanied by a medical evaluation and conclusion.
• AHV <5 cm/year at screening (Phase II only);
• BA < CA at screening (Phase II only);
• IGF-1 SDS ≤ -1.0 at screening (Phase II only).

Критерии исключения

• Presence of one or more pituitary hormone deficiencies in addition to growth hormone deficiency.
• Any suspected or known disease likely to affect growth, or any clinically significant abnormality that would preclude the accurate assessment of standing height (Phase II only), including but not limited to:

• 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.
• Congenital abnormalities causing skeletal abnormalities, or claudication (Phase II only).
• Significant spinal abnormalities (Phase II only).
• 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.
• 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.
• 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.
• 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 glucocorticoid therapy at a dose greater than 400 µg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening (Phase II only).
• Receipt within 3 months prior to screening or planned use during the study of medications that may interfere with growth or development (Phase II only).
• 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: NCT07450001 · GenSci134-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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