A Trial of YPEG-rhGH in Children With Short Stature

NCT05838885 | Completed Phase 2

• 1 other identifier: TB2106GH
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

Idiopathic Short Stature; Small for Gestational Age; Turner Syndrome

Keywords

Growth hormone; Somatotropin; Short stature; Idiopathic short stature; Small for gestational age; Turner syndrome

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (6)

• 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

Study Arms (4)

YPEG-GH low dose group

EXPERIMENTAL

Drug: YPEG-rhGH

YPEG-GH high dose group

EXPERIMENTAL

Drug: YPEG-rhGH

rhGH low dose group

ACTIVE COMPARATOR

Drug: rhGH

rhGH high dose group

ACTIVE COMPARATOR

Drug: rhGH

Interventions

YPEG-rhGH DRUG

YPEG-rhGH, 140μg/kg, s.c., once a week, for 52 weeks

YPEG-GH low dose group

rhGH DRUG

rhGH, 245μg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks

rhGH low dose group

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Prepubertal (Tanner I), aged older than 4 years and younger than10 years for girls and 11 years for boys.
• Body weight: 12kg ≤ body weight ≤ 50kg.
• 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.
• 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.
• 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.
• 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).

You may not qualify if:

• For children with small for gestational: confirmed or suspected Bloom syndrome.
• For children with Turner syndrome: containing a Y chromosome or a fragment derived from a Y chromosome.
• Children with closed epiphysis.
• 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.
• 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.
• 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.
• Children with abnormal values of liver and kidney function (ALT \> 1.5 ULN, Cr \> 1 ULN).
• Concomitant with chronic hepatitis B, AIDS, tuberculosis, and any other chronic infectious disease.
• Patients with severe allergic constitutions or allergic to growth hormone or its excipients such as mannitol, lysine, sodium chloride and other ingredients.
• Patients with a previous history of malignancy or are currently suffering from active malignancy, including intracranial tumors.
• Patients with abnormal glucose regulation (including abnormal fasting glucose and/or abnormal glucose tolerance) or diabetes.
• Patients who are mentally ill or have a family history of mental illness.
• Patients who are suffering from chronic systemic diseases, such as malnutrition, immunocompromised individuals, asthma, etc.
• Patients with congenital intracranial hypertension.
• Patients with slipped capital femoral epiphysis (SCFE).

Sponsors & Collaborators

• Xiamen Amoytop Biotech Co., Ltd.: lead
• Tongji Hospital: collaborator

Study Sites (19)

The Fourth Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Location

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Location

The Third Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Location

Sanya Central Hospital (Hainan Third People's Hospital)

Sanya, Hainan, China

Location

Henan Children's Hospital Zhengzhou Children's Hospital

Zhengzhou, Henan, China

Location

Tongji Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Location

Wuhan Children's Hospital

Wuhan, Hubei, China

Location

Hunan Children's Hospital

Changsha, Hunan, China

Location

Children's Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Location

Children's Hospital of Soochow University

Suzhou, Jiangsu, China

Location

Affiliated Hospital of Jiangnan University

Wuxi, Jiangsu, China

Location

Jiangxi Provincial Children's Hospital

Nanchang, Jiangxi, China

Location

Chengdu Women's and Children's Central Hospital

Chengdu, Sichuan, China

Location

West China Second University Hospital, Sichuan University

Chengdu, Sichuan, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Location

Children's Hospital, Capital Institute of Pediatrics

Beijing, China

Location

Children's Hospital of Shanghai

Shanghai, China

Location

MeSH Terms

Conditions

Turner Syndrome; Dwarfism

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: May 3, 2023
• Study Start: February 15, 2022
• Primary Completion: October 23, 2023
• Study Completion: December 19, 2023
• Last Updated: January 24, 2024

Record last verified: 2024-01

Locations

CN (19)