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

Sponsor

Xiamen Amoytop Biotech Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04513171

Collaborator

Tongji Hospital (Other)

400

Enrollment

Location

Arms

59.2

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Deficiency	Drug: Y-shape pegylated somatropin Drug: Y-shape pegylated somatropin Drug: Y-shape pegylated somatropin Drug: Norditropin® Drug: Y-shape pegylated somatropin Drug: Norditropin	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 26, 2018

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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.
Experimental: Y-shape pegylated somatropin middle dose	Drug: Y-shape pegylated somatropin Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.
Experimental: Y-shape pegylated somatropin high dose	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 140μg/kg, subcutaneous injection, Once weekly.
Active Comparator: Norditropin-2	Drug: Norditropin Norditropin 245μg/kg/week, subcutaneous injection, Once daily.

Outcome Measures

Primary Outcome Measures

Phase 2: Change of areas under the curve of IGF-1 concentration from baseline (ΔIGF-1 AUC). [12 weeks]
Phase 3: Change of annualized height velocity from baseline. [52 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 11 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.