Clinical trial NCT03635580: Efficacy and Safety of rhGH (Jintropin®) in Pediatric Participants With ISS
Official title: Phase 2 Study of Efficacy and Safety of rhGH (Jintropin®) in Pediatric Participants With ISS (Idiopathic Short Stature): a 52-week Multicenter, Open-label, Randomized, Negative Controlled Study Followed by a 52-week Open-label Period
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Dwarfism
Lead sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The Children's Hospital of Zhejiang University School of Medicine
name: First Affiliated Hospital, Sun Yat-Sen University
name: Second Affiliated Hospital of Xi'an Jiaotong University
name: Henan Provincial People's Hospital
name: Children's Hospital of Fudan University
name: The First Affiliated Hospital with Nanjing Medical University
name: Shanxi Provincial Maternity and Children's Hospital
name: The First Hospital of Jilin University
name: Shanghai Children's Hospital
First posted: 2018-08-17
Enrollment: 480
Sex: ALL
Minimum age (years): 4
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase 1: To evaluate the safety and efficacy of 0.05mg/kg/d of rhGH (Jintropin®) in the treatment of children with idiopathic short stature (ISS) in 52 weeks.

Phase 2: To evaluate the safety and efficacy of rhGH (Jintropin®) in the treatment of children with ISS in 2 years


Eligibility criteria: Inclusion Criteria:

* Boys are between 4 and 10 years old age and girls are between 4 and 9 years old age;
* Height \<-2.25 SD (Standard deviation) for chronological age;
* GH (Growth hormone) peak concentration ≥10.0 ng/mL in GH stimulation tests;
* The bone age (BA) ≤chronological age (CA)+6 months;
* Prepubertal Status (Tanner Stage I);
* Birth weight within the normal range;
* Growth hormone treatment-naive;
* Participants are willing and able to cooperate to complete scheduled visits, treatment plans and laboratory tests and other procedures, to sign informed consent.

Exclusion Criteria:

* Participants with abnormal liver and kidney functions (ALT \> upper limit 1.5 times of normal value; Cr \> upper limit of normal value);
* Participants are positive for anti-HBc, HbsAg or HbeAg in Hepatitis B virus tests;
* Participants with known highly allergic constitution or allergy to investigational product or its excipient;
* Participants with systemic chronic disease and immune deficiency;
* Participants diagnosed with tumor, or with potential high tumor risks such as tumor markers exceed normal range and some other relative information may be excluded from the treatment;
* Participants with mental disease;
* Participants with other types of abnormal growth and development;

  1. Growth hormone deficiency (GHD) (confirmed by GH stimulation test);
  2. Turner syndrome (confirmed by karyotype test of girls);
  3. Noonan syndrome (hypertelorism, pectus carinatum, hypophrenia, frequently with skin disease and congenital heart disease, missense mutation of the protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene on chromosome 12 for half of the participants, for both male and female participants);
  4. Laron syndrome (confirmed by IGF-1 generation test);
  5. Small for gestational age ( the birth height or weight is below the tenth percentile or 2 SD, with catch-up growth uncompleted at 2 years old);
  6. Growth disorders caused by malnutrition or hypothyroidism (thyroid function test).
* Participants with impaired glucose regulation (IGR) (including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) ) or diabetes;
* BMI (Body mass index) ≥22kg/m²;
* Congenital skeletal abnormalities or scoliosis, claudication;
* Participants who took part in other clinical trials within 3 months;
* Participants who received medications which may interfere GH secretion or GH function, or other hormones within 3 months (such as sex steroids, glucocorticoids, etc.);
* Other conditions which is inappropriate for this study in the opinion of the investigator.

Primary outcomes:
measure: ΔHtSDSca (The change of height standard deviation score of chronological age before and after treatment)
timeFrame: Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2.
Secondary outcomes:
measure: ΔHT (Change of height)
timeFrame: Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2.
measure: △BA/CA (bone age change / chronological age)
timeFrame: Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2.
measure: Yearly growth velocity
timeFrame: Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2.
measure: ΔIGF-1 SDS (Change of insulin-like growth factor 1 standard deviation score)
timeFrame: Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Children's Hospital
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Taiyuan
country: China
facility: Children's Hospital of Shanxi
state: Shanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Hangzhou
country: China
facility: The Children's Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Shanghai
country: China
facility: Children's Hospital of Shanghai
Study officials:
affiliation: The Children's Hospital of Zhejiang University School of Medicine
name: Junfen Fu, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yuan J, Fu J, Wei H, Zhang G, Xiao Y, Du H, Gu W, Li Y, Chen L, Luo F, Zhong Y, Gong H. A Randomized Controlled Phase 3 Study on the Efficacy and Safety of Recombinant Human Growth Hormone in Children With Idiopathic Short Stature. Front Endocrinol (Lausanne). 2022 Apr 29;13:864908. doi: 10.3389/fendo.2022.864908. eCollection 2022.