Clinical trial NCT05838885: A Trial of YPEG-rhGH in Children With Short Stature
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Xiamen Amoytop Biotech Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Tongji Hospital
First posted: 2023-05-03
Enrollment: 78
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic-area under plasma concentration versus time curve
timeFrame: up to 52 weeks
measure: Pharmacokinetic-maximum serum concentration
timeFrame: up to 52weeks
measure: Pharmacokinetic-time to reach the maximum plasma concentration
timeFrame: up to 52 weeks
measure: Pharmacokinetic-terminal disposition phase half-life
timeFrame: up to 52 weeks
measure: Pharmacokinetic-terminal elimination rate constant
timeFrame: up to 52 weeks
measure: Pharmacokinetic-apparent clearance after extravascular administration
timeFrame: up to 52 weeks
measure: Pharmacokinetic-apparent volume of distribution
timeFrame: up to 52 weeks
Secondary outcomes:
measure: Pharmacodynamics-the properties of Insulin-like growth facto1 and Insulin-like growth factor binding receptor 3.
timeFrame: up to 57 weeks
measure: Height velocity (HV, cm/year)
timeFrame: At 52 weeks of treatment
measure: Change of height velocity compared to baseline (ΔHV, cm/year)
timeFrame: At 52 weeks of treatment
measure: Height standard deviation according to chronological age (Ht SDS CA)
timeFrame: At 52 weeks of treatment
measure: Change in bone age
timeFrame: At 52 weeks of treatment
measure: Adverse events (including injection site reactions), changes from baseline in vital signs and laboratory tests
timeFrame: up to 57 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Fourth Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Sanya
country: China
facility: Sanya Central Hospital (Hainan Third People's Hospital)
state: Hainan
city: Zhengzhou
country: China
facility: Henan Children's Hospital Zhengzhou Children's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Wuhan Children's Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Nanjing
country: China
facility: Children's Hospital of Nanjing Medical University
state: Jiangsu
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial Children's Hospital
state: Jiangxi
city: Chengdu
country: China
facility: Chengdu Women's and Children's Central Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Second University Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Beijing
country: China
facility: Children's Hospital, Capital Institute of Pediatrics
city: Shanghai
country: China
facility: Children's Hospital of Shanghai
Study officials:
References: