A Study of PEG-somatropin in the Treatment of Children With Idiopathic Short Stature

Pegylated Somatropin (PEG Somatropin) in the Treatment of Children With Idiopathic Short Stature: A Controlled, Prospective, Randomized, Multicenter Phase-II Study With An Untreated Control Group.

This study aims to explore the optimal dose of pegylated recombinant human growth hormone (PEG-rhGH) injection to treat children with idiopathic short stature (ISS), evaluate its safety and efficacy, and provide scientific and reliable evidence for the medication dosage in Phase III clinical study.

Study Overview

• Status: Unknown
• Conditions: Dwarfism
• Intervention / Treatment: Drug: Jintrolong® low dose group; Drug: Jintrolong® high dose group

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Children's Hospital
  • Shanghai, China
    • Recruiting
    • Shanghai Children's Hospital of Fudan University
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • The First Affiated Hospital of Nanjing Medical University
    • Wuxi, Jiangsu, China
      • Recruiting
      • Affiliated Hospital of Jiangnan University
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • The First Hospital of Jilin University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The Children's Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Boys are between 4 and 9 years of age and girls are between 4 and 8 years of age.
• Height <-2 SD for chronological age.
• Growth velocity<5.0 cm/yr.
• GH peak concentration ≥10.0 ng/mL in two different stimulation tests.
• The difference of bone age (BA) and chronological age (CA) is within -2 to +2.
• IGF-1 concentration is between -2 SDS to +2 SDS.
• Prepubertal Status(Tanner Stage I).
• Birth weight within the normal range.
• Growth hormone treatment-naive.
• Subjects are willing and able to cooperate to complete scheduled visits, treatment plans and laboratory tests and other procedures, to sign informed consent.

Exclusion Criteria:

• Subjects with abnormal liver and kidney functions (ALT > upper limit of normal value; Cr > upper limit of normal value).
• Subjects are positive for anti-HBc, HbsAg or HbeAg in Hepatitis B virus tests.
• Subjects with known highly allergic constitution or allergy to investigational product or its excipient.
• Subjects with systemic chronic disease and immune deficiency.
• Patients diagnosed with tumor.
• Patients with mental disease.

• Patients 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 patients, for both male and female patients);
  4. Laron sydrome (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).
• Growth disorders caused by malnutrition or hypothyroidism (thyroid function test).
• Congenital skeletal abnormalities or scoliosis, claudication.
• Subjects with impaired glucose regulation (IGR) (including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) ) or diabetes).
• Subjects with abnormal electrolyte, blood gas analysis (vein), creatine kinase.
• Subjects who took part in other clinical trials within 3 months.
• Subjects who received medications which may interfere GH secretion or GH function, or other hormones within 3 months (such as sex steroids, glucocorticoids, etc.).
• For patients with potential high tumor risks such as tumor markers exceed normal range and some other relative information, they may be excluded from the treatment.
• Other conditions which is inappropriate for this study in the opinion of the investigator.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Jintrolong® low dose group; PEG-rhGH Injection (27IU/4.5mg/0.5ml/bottle) 0.1 mg/kg/w by subcutaneous injection for 52 weeks.	Drug: Jintrolong® low dose group; PEG-somatropin 0.1mg/kg/wk by weekly subcutaneous injection for 52 weeks.; Other Names: PEG-somatropin; Drug: Jintrolong® high dose group; PEG-somatropin 0.2 mg/kg/wk by weekly subcutaneous injection for 52 weeks.; Other Names: PEG-somatropin
Experimental: Jintrolong® high dose group; PEG-rhGH Injection (27IU/4.5mg/0.5ml/bottle) 0.2 mg/kg/w by subcutaneous injection for 52 weeks.	Drug: Jintrolong® low dose group; PEG-somatropin 0.1mg/kg/wk by weekly subcutaneous injection for 52 weeks.; Other Names: PEG-somatropin; Drug: Jintrolong® high dose group; PEG-somatropin 0.2 mg/kg/wk by weekly subcutaneous injection for 52 weeks.; Other Names: PEG-somatropin
No Intervention: Negative control group; Untreated Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Height Standard Deviation Score for Chronological Age (ΔHtSDSCA)	Change in Height Standard Deviation Score for Chronological Age (ΔHtSDSCA) from Baseline to 52 weeks；ΔHtSDSCA=(height Yx - reference mean for CA Yx) / reference SD for CA Yx (Yx refers to the height value at particular timepoint x)	Baseline，52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Annualized Height Velocity	Annualized Height Velocity=12×(Height Yx - Height at Baseline)/(Date of Yx - Date of Baseline) (Yx refers to the height value at particular timepoint x)	Baseline，52 weeks
Change in Bone Maturation	Bone Maturation=(BA Yx-BA at Baseline)/(Date of Yx - Date of Baseline) (Yx refers to the BA value at particular timepoint x)	Baseline，52 weeks
Change in IGF-1 Standard Deviation Score (IGF-1 SDS)	GF-1 SDS=(IGF-1 Yx - reference mean for CA Yx) / reference SD for CA Yx (Yx refers to the IGF-1 value at particular timepoint x)	Baseline，52 weeks
IGF-1/IGFBP-3 molar ratio at 52 weeks	IGF-1/IGFBP-3 molar ration=[IGF-1(ng/ml)/7.6]/[IGFBP-3 (ng/ml)/25.75]	Baseline，52 weeks

Collaborators and Investigators

• Sponsor: GeneScience Pharmaceuticals Co., Ltd.
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Tongji Hospital; Affiliated Hospital of Jiangnan University; Children's Hospital of Fudan University; Shanghai Children's Hospital; The First Hospital of Jilin University; The Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: July 14, 2017
• First Submitted That Met QC Criteria: July 14, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Dwarfism
• Other Study ID Numbers: GenSci 033 CT-one year

Drug and device information, study documents

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