A Trial of YPEG-rhGH in Children With Short Stature

A Multicenter, Randomized, Open-label, Positive-controlled Phase 2 Study to Explore the Optimal Dose of Y- Shaped Pegylated Recombinant Growth Hormone (YPEG-rhGH) in Children With Short Stature (ISS, SGA, TS)

To explore the dose-response relationship between pharmacokinetics and pharmacodynamics of Y- Shaped Pegylated growth hormone injection (YPEG-GH) in children with short stature (idiopathic short stature (ISS), small for gestational age (SGA), Turner syndrome (TS)).

To evaluate its tolerability, safety and efficacy and to provide evidence for dose selection and titration for future clinical development and clinical application in these population.

Study Overview

• Status: Completed
• Conditions: Turner Syndrome; Small for Gestational Age; Idiopathic Short Stature
• Intervention / Treatment: Drug: YPEG-rhGH; Drug: YPEG-rhGH; Drug: rhGH; Drug: rhGH

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Children's Hospital, Capital Institute of Pediatrics
  • Shanghai, China
    • Children's Hospital of Shanghai
  • Anhui
    • Hefei, Anhui, China
      • The Second Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • The Fourth Affiliated Hospital of Anhui Medical University
  • Fujian
    • Xiamen, Fujian, China
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • The Third Affiliated Hospital, Sun Yat-Sen University
  • Hainan
    • Sanya, Hainan, China
      • Sanya Central Hospital (Hainan Third People's Hospital)
  • Henan
    • Zhengzhou, Henan, China
      • Henan Children's Hospital Zhengzhou Children's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College of HUST
    • Wuhan, Hubei, China
      • Wuhan Children's Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Children's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Children's hospital of Nanjing medical university
    • Suzhou, Jiangsu, China
      • Children's Hospital of Soochow University
    • Wuxi, Jiangsu, China
      • Affiliated Hospital of Jiangnan University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial Children's Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Chengdu Women's and Children's central hospital
    • Chengdu, Sichuan, China
      • West China Second University Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Prepubertal (Tanner I), aged older than 4 years and younger than10 years for girls and 11 years for boys.
2. Body weight: 12kg ≤ body weight ≤ 50kg.
3. For children with idiopathic short stature: a) Birth length and weight were at the 10th percentile and above of normal reference values for infants of the same gestational age and sex; b) Height at screening was 2.0 standard deviations (SD) below the mean height for chronological age and sex c) Exclude other causes such as systemic diseases, other endocrine diseases, nutritional diseases, chromosomal abnormalities, skeletal dysplasia, psycho-emotional disorders, etc. were excluded d) GH peak ≥10.0ng/ml confirmed by two different drug GH provocation tests; e) Bone age (BA)-chronological age (CA) ≤1 year.
4. For children with small for gestational age: a) Birth length and weight were at the 10th percentile and below the normal reference values for infants if the same gestational age and sex; b) Gestational age at birth ≥ 24 weeks; c) Height at screening was below -2 SD of the mean for the same age and sex, and please refer to the protocol annex 1 for height.
5. For children with Turner syndrome: a) Chromosome karyotype: 45, X; 45, X/46, XXqi; 45, X/46, XXr; 45, X/46, XX; 46, XXqi; 46, XXpi; 45, X/47, XXX; 46, XXp-; 45, X/46, XXp-; 46, XXq-; 45, x/46, XXq-; 45, X/46, XX/47, XXX, etc.; b) Having at least one specific physical characteristic: Including but not limited to low posterior hairline, facial skin nevus, neck flips, short neck, low ear position, small jaw, high palatal arch, shield chest, wide breast spacing, elbow ectropion, knee ectropion, short 4th and 5th metacarpal, nail dysplasia, scoliosis, ptosis, strabismus, cardiovascular system abnormalities such as aortic stenosis, bicuspid aortic valve, hypertension, and reproductive system abnormalities such as primary gonadal insufficiency, renal malformation, hypothyroidism and middle ear disease; c) The height at screening was below the mean -2SD of the same age and gender, and please refer to the protocol annex 1 for height.
6. Understands and signs the informed consent form voluntarily by the subject's parent(s) and/or legal guardian(s). And written assent of the subject is required if the subject is 8 years of age or older).

Exclusion Criteria:

1. For children with small for gestational: confirmed or suspected Bloom syndrome.
2. For children with Turner syndrome: containing a Y chromosome or a fragment derived from a Y chromosome.
3. Children with closed epiphysis.
4. Children who diagnosed or highly suspected growth hormone deficiency (GHD), or other types of growth abnormalities: e.g., Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, etc.
5. Children who have previously received systemic growth-promoting therapy, including but not limited to rhGH, aromatase inhibitors, sex hormones, etc., for at least 1 month or longer.
6. Children who are now receiving or plan to receive the therapy of glucocorticoids, methylphenidate, and any other drugs that may have an effect on growth.
7. Children with abnormal values of liver and kidney function (ALT > 1.5 ULN, Cr > 1 ULN).
8. Concomitant with chronic hepatitis B, AIDS, tuberculosis, and any other chronic infectious disease.
9. Patients with severe allergic constitutions or allergic to growth hormone or its excipients such as mannitol, lysine, sodium chloride and other ingredients.
10. Patients with a previous history of malignancy or are currently suffering from active malignancy, including intracranial tumors.
11. Patients with abnormal glucose regulation (including abnormal fasting glucose and/or abnormal glucose tolerance) or diabetes.
12. Patients who are mentally ill or have a family history of mental illness.
13. Patients who are suffering from chronic systemic diseases, such as malnutrition, immunocompromised individuals, asthma, etc.
14. Patients with congenital intracranial hypertension.
15. Patients with slipped capital femoral epiphysis (SCFE).
16. Patients with scoliosis exceeding 15°;
17. Patients who have participated in any drug clinical study (as a subject) within 3 months prior to screening and have received a drug intervention
18. Patients who the investigators considered unfit for 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YPEG-GH low dose group	Drug: YPEG-rhGH; YPEG-rhGH, 140μg/kg, s.c., once a week, for 52 weeks; Drug: YPEG-rhGH; YPEG-rhGH, 280μg/kg, s.c., once a week, for 52 weeks
Experimental: YPEG-GH high dose group	Drug: YPEG-rhGH; YPEG-rhGH, 140μg/kg, s.c., once a week, for 52 weeks; Drug: YPEG-rhGH; YPEG-rhGH, 280μg/kg, s.c., once a week, for 52 weeks
Active Comparator: rhGH low dose group	Drug: rhGH; rhGH, 245μg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks; Drug: rhGH; rhGH, 470μg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks
Active Comparator: rhGH high dose group	Drug: rhGH; rhGH, 245μg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks; Drug: rhGH; rhGH, 470μg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic-area under plasma concentration versus time curve	up to 52 weeks
Pharmacokinetic-maximum serum concentration	up to 52weeks
Pharmacokinetic-time to reach the maximum plasma concentration	up to 52 weeks
Pharmacokinetic-terminal disposition phase half-life	up to 52 weeks
Pharmacokinetic-terminal elimination rate constant	up to 52 weeks
Pharmacokinetic-apparent clearance after extravascular administration	up to 52 weeks
Pharmacokinetic-apparent volume of distribution	up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics-the properties of Insulin-like growth facto1 and Insulin-like growth factor binding receptor 3.	up to 57 weeks
Height velocity (HV, cm/year)	At 52 weeks of treatment
Change of height velocity compared to baseline (ΔHV, cm/year)	At 52 weeks of treatment
Height standard deviation according to chronological age (Ht SDS CA)	At 52 weeks of treatment
Change in bone age	At 52 weeks of treatment
Adverse events (including injection site reactions), changes from baseline in vital signs and laboratory tests	up to 57 weeks

Collaborators and Investigators

• Sponsor: Xiamen Amoytop Biotech Co., Ltd.
• Collaborators: Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): October 23, 2023
• Study Completion (Actual): December 19, 2023

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 3, 2023

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; Small for gestational age; Turner syndrome; Idiopathic short stature; Somatotropin; Short stature
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Chromosome Disorders; Bone Diseases, Developmental; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Turner Syndrome; Gonadal Dysgenesis; Dwarfism
• Other Study ID Numbers: TB2106GH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No