A Study to Evaluating the Efficacy and Safety of Recombinant Long-acting Human Growth Hormone (TJ101) in Children With Growth Hormone Deficiency

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

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.

Study Overview

• Status: Completed
• Conditions: Pediatric Growth Hormone Deficiency
• Intervention / Treatment: Drug: TJ101; Drug: NordiFlex

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoping Luo; Phone Number: 13387522645; Email: xpluo@sina.com
• Study Contact Backup: Name: Wei Wu; Phone Number: 13871186026; Email: wuweir11@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Second Affiliated hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Beijing Children's Hospital,Capital Medical University
    • Beijing, Beijing, China
      • Children's Hospital, Capital Institute of Paediatrics
  • Chongqing
    • Wanzhou, Chongqing, China
      • Chongqing Three Gorges Central Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China
      • The Third Affiliated Hospital of Sun Yet-sen University
  • Guangxi
    • Liuzhou, Guangxi, China
      • Liuzhou Maternity and Children Healthcare Hospital
  • Hainan
    • Sanya, Hainan, China
      • Hainan Third People's Hospital
  • Hebei
    • Tangshan, Hebei, China
      • Tangshan Women and Children's Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Children's Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China
      • Wuhan Children's Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Children's Hospital
    • Hengyang, Hunan, China
      • The First Affiliated Hospital of Nanhua University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Children's Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China
      • Jiangsu Provincial Maternal and Child Health Hospital
    • Suzhou, Jiangsu, China
      • Children's Hospital affiliated to Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial Children's Hospital
    • Pingxiang, Jiangxi, China
      • Pingxiang Maternity and Child Care Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Bethune Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China
      • ShengJing Hospital Of China Medical University
  • Ningxia
    • Yinchuan, Ningxia, China
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jining, Shandong, China
      • Affiliated Hospital of Jining Medical College
    • Linyi, Shandong, China
      • Linyi Women and Children's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Children's Medical Center
    • Shanghai, Shanghai, China
      • Shanghai Jiaotong University School of Medicine Ruijin Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Chengdu Women's and Children's Central Hospital
    • Chengdu, Sichuan, China
      • West China Second Hospital of Sichuan University
  • Zhejiang
    • Liuzhou, Zhejiang, China
      • Taizhou First People's Hospital
    • Ningbo, Zhejiang, China
      • Ningbo Women & Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TJ101; TJ101 1.2 mg/kg once a week for 52weeks	Drug: TJ101; TJ101/ Recombinant Human Somatropin Injection treatment: after screening, subjects will be randomized to receive TJ101 1.2 mg/kg once a week until 52 weeks back site, investigator evaluate effectiveness and safety.
Active Comparator: NordiFlex; NordiFlex Injection 0.034 mg/kg once a day for 52 weeks	Drug: NordiFlex; TJ101/ Recombinant Human Somatropin Injection treatment: after screening, subjects will be randomized to receive Recombinant Human Somatropin Injection 0.034 mg/kg once a day, until 52 weeks back site, investigator evaluate effectiveness and safety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Annualized Height velocity at 52 week	The Annualized Height velocity at 52 week	52weeks after first dose

Secondary Outcome Measures

Outcome Measure	Time Frame
change in Annualized Height velocity at 26 week (compared to Baseline value)	26weeks after first dose
change in Annualized Height velocity at 52 week (compared to Baseline value)	52weeks after first dose

Collaborators and Investigators

• Sponsor: TJ Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: CTJ101PGHD301

Drug and device information, study documents

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