A Trial of YPEG-rhGH in Children With Short Stature

Turner Syndrome Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05838885
• Other study ID #: TB2106GH
• Status: Completed
• Phase: Phase 2
• Start date: February 15, 2022
• Est. completion date: December 19, 2023

Study information

• Verified date: January 2024
• Source: Xiamen Amoytop Biotech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 19, 2023
• Est. primary completion date: October 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dwarfism
• Gonadal Dysgenesis
• Idiopathic Short Stature
• Small for Gestational Age
• Turner Syndrome

Intervention

Drug:
• YPEG-rhGH
YPEG-rhGH, 140µg/kg, s.c., once a week, for 52 weeks
• YPEG-rhGH
YPEG-rhGH, 280µg/kg, s.c., once a week, for 52 weeks
• rhGH
rhGH, 245µg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks
• rhGH
rhGH, 470µg/kg/week, divided into 7 subcutaneous injections, once daily, for 52 weeks

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Xiamen Amoytop Biotech Co., Ltd.	Tongji Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic-area under plasma concentration versus time curve		up to 52 weeks
Primary	Pharmacokinetic-maximum serum concentration		up to 52weeks
Primary	Pharmacokinetic-time to reach the maximum plasma concentration		up to 52 weeks
Primary	Pharmacokinetic-terminal disposition phase half-life		up to 52 weeks
Primary	Pharmacokinetic-terminal elimination rate constant		up to 52 weeks
Primary	Pharmacokinetic-apparent clearance after extravascular administration		up to 52 weeks
Primary	Pharmacokinetic-apparent volume of distribution		up to 52 weeks
Secondary	Pharmacodynamics-the properties of Insulin-like growth facto1 and Insulin-like growth factor binding receptor 3.		up to 57 weeks
Secondary	Height velocity (HV, cm/year)		At 52 weeks of treatment
Secondary	Change of height velocity compared to baseline (?HV, cm/year)		At 52 weeks of treatment
Secondary	Height standard deviation according to chronological age (Ht SDS CA)		At 52 weeks of treatment
Secondary	Change in bone age		At 52 weeks of treatment
Secondary	Adverse events (including injection site reactions), changes from baseline in vital signs and laboratory tests		up to 57 weeks