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

NCT ID: NCT04513171

Last Updated: 2024-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 434 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-26
• Study Completion Date: 2023-07-10

Brief Summary

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.

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.

Conditions

Growth Hormone Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Y-shape pegylated somatropin low dose

Group Type: EXPERIMENTAL

Y-shape pegylated somatropin

Intervention Type: DRUG

Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.

Y-shape pegylated somatropin middle dose

Group Type: EXPERIMENTAL

Y-shape pegylated somatropin

Intervention Type: DRUG

Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.

Y-shape pegylated somatropin high dose

Group Type: EXPERIMENTAL

Y-shape pegylated somatropin

Intervention Type: DRUG

Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.

Norditropin-1

Group Type: ACTIVE_COMPARATOR

Norditropin®

Intervention Type: DRUG

Norditropin 245μg/kg/week, subcutaneous injection, Once daily.

Y-shape pegylated somatropin optimal dose

Group Type: EXPERIMENTAL

Y-shape pegylated somatropin

Intervention Type: DRUG

Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.

Norditropin-2

Group Type: ACTIVE_COMPARATOR

Norditropin

Intervention Type: DRUG

Norditropin 245μg/kg/week, subcutaneous injection, Once daily.

Interventions

Y-shape pegylated somatropin

Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.

Intervention Type: DRUG

Y-shape pegylated somatropin

Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.

Intervention Type: DRUG

Y-shape pegylated somatropin

Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.

Intervention Type: DRUG

Norditropin®

Norditropin 245μg/kg/week, subcutaneous injection, Once daily.

Intervention Type: DRUG

Y-shape pegylated somatropin

Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.

Intervention Type: DRUG

Norditropin

Norditropin 245μg/kg/week, subcutaneous injection, Once daily.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tongji Hospital

OTHER

Sponsor Role: collaborator

Xiamen Amoytop Biotech Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiaoping Luo, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

Tongji Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 36034448 (View on PubMed)

Other Identifiers

TB1805GH

Identifier Type: -

Identifier Source: org_study_id