Clinical trial NCT04633057: A Study to Evaluating the Efficacy and Safety of Recombinant Long-acting Human Growth Hormone (TJ101) in Children With Growth Hormone Deficiency
Official title: A Phase III, Randomized, Open-label, Positive-controlled, Multi-center Study to Evaluating the Efficacy and Safety of Recombinant Long-acting Human Growth Hormone (TJ101) in Children With Growth Hormone Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pediatric Growth Hormone Deficiency
Lead sponsor: TJ Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-18
Enrollment: 168
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase III, Randomized, open-label, positive-drug parallel control, Study to Evaluate the Efficacy and Safety of TJ101 in Child subject with growth hormone deficieney.


Eligibility criteria: Inclusion Criteria:

1. Boys: 3 years ≤ boy's age ≤ 10 years；Girls: 3 years ≤ girl's age ≤ 9 years
2. Pre-pubertal children(Tanner stage I)
3. GHD confirmed by 2 different GH provocation tests with peak GH concentration below 10 ng/mL in screening or one month
4. Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age (CA) and gender according to Table of standard deviation unit values of age and height of Chinese children aged 3-12 years , (HT SDS ≤ -2.0)
5. Height velocity≤5.0cm/years (Including height records before at least three months)；
6. IGF-1 SDS≤-1.0
7. Bone age (BA) is no more than two chronological age
8. Body mass Index (BMI) must be within ±2 SD of mean BMI for the chronological age and sex according to Table of standard deviation unit values of Age and BMI of Chinese children aged 3-12 years
9. Without prior exposure to any rhGH therapy
10. For children with growth hormone deficiency that is one of its multiple pituitary hormone deficiencies, alternative therapies targeting the hypothalamus-pituitary-target gland axis must be used for at least 3 months before screening
11. Written informed consent of the parent or legal guardian of the subject and assent of the subject (if the subject can read)

Exclusion Criteria:

1. beyond physiological dosage of glucocorticoid therapy
2. Evidence of closed epiphyses
3. Any other chronic condition that can cause short stature and cannot be treated with hormone replacement therapy(Including but not limited Chronic kidney disease, malnutrition, absorption disorders, uncontrolled hypothyroidism, celiac disease, rickets and social-psychological dwarfism)
4. Abnormal liver and renal function (ALT\>1.5 times the upper limit of normal range and Cr exceeding the upper limit of normal range)
5. Presence of anti-hGH antibodies at screening
6. Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, with the exception of ADHD(attention deficit hyperactivity disorder) drug hormone replacement therapies \[thyroxine, hydrocortisone, desmopressin (DDAVP)\]
7. Mutations in growth hormone receptors are suspected, or any syndrome that causes insensitivity to growth hormone
8. At screening, ophthalmologic examination (including fundus microscopy) indicated increased intracranial pressure and/or retinopathy.
9. At screening, previous or existing intracranial tumor growth was confirmed by cranial magnetic resonance imaging (MRI) scan (using contrast agent) (MRI results up to 1 year prior to screening were acceptable)
10. Diseases such as severe cardiopulmonary, blood system, malignant tumor or potential tumor (family history), or systemic infection, low immune function and mental diseases
11. Significant spinal abnormalities, including scoliosis (Cobb Angle \& GT;60 ˚), kyphosis and spina bifida.
12. Subjects diagnosed with type 2 or type 1 diabetes who were considered to have received no standard treatment, did not follow their prescribed treatment, or exhibited poor metabolic control, or had fasting glucose \> 5.6 mmol/L twice in a row
13. Chromosomal abnormalities and medical syndromes (Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, SHOX mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia
14. Children with low birth weight (birth weight and/or body length are 2 SD below average according to the standard of the general Chinese population of the same gestational age and sex)
15. The subject and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct
16. Subject who has received an investigational product or has participated in a clinical study within 30 days before screening or during the clinical trials.
17. Known or suspected to be HIV positive, serologically positive for syphilis, or other chronic infectious diseases, such as AIDS, tuberculosis, hepatitis, etc
18. The history of drug, drug or alcohol abuse
19. Other conditions not considered suitable for inclusion by the researchers

Primary outcomes:
measure: The Annualized Height velocity at 52 week
timeFrame: 52weeks after first dose
Secondary outcomes:
measure: change in Annualized Height velocity at 26 week (compared to Baseline value)
timeFrame: 26weeks after first dose
measure: change in Annualized Height velocity at 52 week (compared to Baseline value)
timeFrame: 52weeks after first dose
Other outcomes:
Locations:
city: Hefei
country: China
facility: Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Children's Hospital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Children's Hospital, Capital Institute of Paediatrics
state: Beijing
city: Wanzhou
country: China
facility: Chongqing Three Gorges Central Hospital
state: Chongqing
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 of Sun Yet-sen University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Maternity and Children Healthcare Hospital
state: Guangxi
city: Sanya
country: China
facility: Hainan Third People's Hospital
state: Hainan
city: Tangshan
country: China
facility: Tangshan Women and Children's Hospital
state: Hebei
city: Zhengzhou
country: China
facility: Henan Children's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
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: Hengyang
country: China
facility: The First Affiliated Hospital of Nanhua University
state: Hunan
city: Nanjing
country: China
facility: Children's Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Provincial Maternal and Child Health Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Children's Hospital affiliated to Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial Children's Hospital
state: Jiangxi
city: Pingxiang
country: China
facility: Pingxiang Maternity and Child Care Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical College
state: Shandong
city: Linyi
country: China
facility: Linyi Women and Children's Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine Ruijin Hospital
state: Shanghai
city: Chengdu
country: China
facility: Chengdu Women's and Children's Central Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Second Hospital of Sichuan University
state: Sichuan
city: Liuzhou
country: China
facility: Taizhou First People's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Women & Children's Hospital
state: Zhejiang
Study officials:
References: