Safety and Efficacy of Y-shape Pegylated Somatropin in Growth Hormone Deficiency Children

A Multi-center, Randomized, Positive-control, Phase 2&3 Combined Study of Y-shape Pegylated Somatropin in Prepubertal Children With Growth Hormone Deficiency.

This is a multicenter, randomized, open-labeled, positive controlled phase 2&3 combined study to evaluate the safety and efficacy of weekly Y-shape pegylated somatropin, compared to daily somatropin (Norditropin®), in prepubertal, treatment-naive children with growth hormone deficiency.

Study Overview

• Status: Completed
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Drug: Y-shape pegylated somatropin; Drug: Y-shape pegylated somatropin; Drug: Y-shape pegylated somatropin; Drug: Norditropin®; Drug: Norditropin

Detailed Description

This multicenter, randomized, open-labeled, positive controlled study is divided into two stages. The first one is aimed to exploit the optimal dose of Y-shape pegylated somatropin, while the second one is aimed to confirm the efficacy and safety of the study drug. A total of 400 prepubertal children with growth hormone deficiency were expected to enrolled. Subjects will firstly undergo a 52 weeks treatment, and then followed for 5 weeks.

• Study Type: Interventional
• Enrollment (Actual): 434
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoyan Yi; Phone Number: 86592-6889121; Email: yixiaoyan@amoytop.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College of HUST

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of GHD confirmed by two different GH stimulation tests, defined as a peak of GH level of <10.0 ng/ml, determined with a validated assay. Bone age (BA) at least 2 years less than the chronological age. Growth velocity less than 5.0 cm/year. Impaired HT defined as at least 2.0 standard deviations (SD) below of the mean height for chronological age and sex (HT SDS<-2.0).
• Prepubertal (Tanner Ⅰ) males and females by physical examination, aged older than 3 years and younger than10 years for girls and 11 years for boys.
• Short stature with normal intelligence.
• Baseline IGF-1 level below the median IGF-1 level standardized for age and sex.
• Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is 8 years old or above).

Exclusion Criteria:

• Prior exposure to growth promotion treatment, such as recombinant human growth hormone or gonadal hormones, for more than 1 month.
• Known hypersensitivity to somatropin or excipients, such as mannitol, lysine, sodium chloride.
• Children with closed epiphyses.
• Short stature etiologies other than GHD, such as idiopathic short stature, Turner syndrome, Prader-Willi syndrome, Russell-Silver syndrome, born small for gestational age regardless of GH status.
• Other causes of short stature such as hypothyroidism, adrenocortical hormone deficiency, antidiuretic hormone deficiency.
• Any medical conditions and/or presence that may affect growth velocity such as liver dysfunction, kidney dysfunction, malnutrition, diabetes mellitus, severe dysfunction in major organ such as heart, sever systemic infections, severe immune dysfunction, mental disorders, and other congenital malformations.
• Suffering from chronic infectious diseases such as chronic hepatitis B, AIDS or tuberculosis.
• Receiving non-physiological adrenal corticosteroids.
• Confirmed pituitary and/or hypothalamic malignance by MRI within one year prior to screening. History or presence of any other malignance disease, any evidence of present tumor growth.
• Evidence of congenital intracranial hypertension.
• Evidence of slipped capital femoral epiphysis.
• Evidence of scoliosis over 15°.
• Participation in any other trial of an investigational agent within 3 months prior to screening.
• Any other conditions which in the opinion of the investigator precluded enrollment into the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Y-shape pegylated somatropin low dose	Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.
Experimental: Y-shape pegylated somatropin middle dose	Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.
Experimental: Y-shape pegylated somatropin high dose	Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.
Active Comparator: Norditropin-1	Drug: Norditropin®; Norditropin 245μg/kg/week, subcutaneous injection, Once daily.
Experimental: Y-shape pegylated somatropin optimal dose	Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.; Drug: Y-shape pegylated somatropin; Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.
Active Comparator: Norditropin-2	Drug: Norditropin; Norditropin 245μg/kg/week, subcutaneous injection, Once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2: Change of areas under the curve of IGF-1 concentration from baseline (ΔIGF-1 AUC).	12 weeks
Phase 3: Height velocity.	52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of height standard deviation score according to chronological age.	52 weeks
Change of height standard deviation score according to bone age.	52 weeks
Serum IGF-l level	change from baseline to 52 weeks
Serum IGFBP-3 level	change from baseline to 52 weeks

Collaborators and Investigators

• Sponsor: Xiamen Amoytop Biotech Co., Ltd.
• Collaborators: Tongji Hospital
• Investigators: Principal Investigator: Xiaoping Luo, MD, Ph.D, Tongji Hospital

Publications and helpful links

General Publications

• Liang Y, Zhang C, Wei H, Du H, Zhang G, Yang Y, Zhang H, Gong H, Li P, Song F, Xu Z, He R, Zhou W, Zheng H, Sun L, Luo X. The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency. Front Endocrinol (Lausanne). 2022 Aug 11;13:922304. doi: 10.3389/fendo.2022.922304. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2018
• Primary Completion (Actual): June 7, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Growth Hormone Deficiency; somatropin; recombinated human growth hormone; Growth Hormone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: TB1805GH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No