Clinical trial NCT02375620: Clinical Study of Pegylated Somatropin (PEG Somatropin) to Treat SGA Children With Short Stature
Official title: A Multicenter, Randomized, Open-Label, Dose-Response, Phase II Clinical Study of Pegylated Somatropin (PEG Somatropin) Injection to Treat SGA Children With Short Stature.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Short Stature Children Born Small for Gestational Age (SGA)
Lead sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanxi Provincial Maternity and Children's Hospital
name: Children's Hospital of Fudan University
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: The First Hospital of Jilin University
name: Hunan Children's Hospital
name: Tongji Hospital
name: Affiliated Hospital of Jiangnan University
name: Jiangxi Province Children's Hospital
name: Children's Hospital of The Capital Institute of Pediatrics
First posted: 2015-03-02
Enrollment: 96
Sex: ALL
Minimum age (years): 3
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study was evaluated as the optimal dose for the treatment of SGA short stature children by Pegylated Somatropin, initially evaluated its efficiency and safety for the treatment of SGA short stature children and provided scientific, reliable basis for phase III clinical trials for dose selection.

This is a multicenter, randomized, open-label, dose-response trial, including a 52-week main phase and an ongoing safety extension phase continuing until reaching near-adult height (NAH) in China. Ninety-six growth hormone (GH)-treatment-naïve, non-GH-deficient, prepubertal short children born SGA were randomized in a 1:1 ration to receive weekly subcutaneous administration of Jintrolong 0.1 mg/kg/week or 0.2 mg/kg/week for 52 weeks. Children who completed the 52- week main phase proceeded to the extension phase, while Jintrolong was administered at an initial dose of 0.2 mg/kg/week. Dose adjustments based on annualized height velocity (AHV) and insulin-like growth factor I (IGF-I) response, were made up to a maximum of 0.4 mg/kg/week until achieved NAH or the patient's voluntary discontinuation.


Eligibility criteria: Inclusion Criteria:

* The patients are diagnosed as being clinically full term small for gestational age infant.
* Girl are 3-6 years old, boys are 3-7 years old.
* Be in preadolescence (Tanner stage 1).
* The child did not achieve catch-up growth when he/she entered the group (the definition of catch-up growth is that the height is higher the third percentile with the same age and gender) (Appendix 2 and 3).
* The height of child is shorter than -2SDS of the median of normal children with the same age and gender when he/she entered the group (the mean height and height standard deviation of normal children with the same age and gender of normal children regard the height data in the physical development investigation data of children aged 0-18 in 9 cities of China (2005) as standard \[13\], Appendix 4 and 5).
* Within a year before entering the group, after any growth hormone stimulation test, the peak concentration of growth hormone in serum\>10 µg/L.
* Bone age≤ the actual age+1.
* The function of glucose regulation is normal: fasting blood glucose \< 5.6mmol/L.
* Birth gestational age ≥ 37 weeks.
* The subjects and their guardians sign the informed consent (if the subjects is lack of ability for signing the informed consent, his legal guardian can write the subjects name instead).
* All experimental drug groups completed the main phase (52 weeks) of Phase II clinical trials, and the participants with complete follow-up records can enter the extension phase, provided that the continuous cessation of the use of pegylated recombinant human growth hormone injection lasts ≤ 8 weeks after the end of the first phase treatment and before the start of the extended study.
* Only when the subjects and their guardians are fully informed, express their willingness, and are able to cooperate in completing the treatment, follow-up, and various tests of the extension phase study, and have signed a written informed consent form, can they enter the extension phase trial.

Exclusion Criteria:

* People with abnormal liver or kidney function (ALT\> 2 times the upper limit of normal value, Cr\> the upper limit of normal value).
* Patients are positive for hepatitis B core antigen (HBc), hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg).
* People with known highly allergic constitution or allergy to the drug or the excipient of the study.
* People with diabetes, severe cardiopulmonary, hematological system and malignant tumors diseases or general infection, immune deficiency and patients with mental disease.
* Other abnormal growth and development, such as Turner syndrome, Laron syndrome, growth hormone receptor deficiency.
* Potential tumor patients (family history).
* Patients who used growth hormone for treatment.
* Subjects took part in other clinical trial study within 3 months.
* Patients used other hormonal for treatment within 3 months (such as sex hormone, glucocorticoid and etc., treat for more than a month) and received the drug treatment which may interfere with the secretion of GH or GH function (oxandrolone, growth hormone releasing hormone and etc.);
* Other conditions which in the opinion of the investigator preclude enrollment into the study.
* Subjects who have used the following medications within 2 months prior to entering the expansion phase of the trial:
* 1) Aromatase inhibitors (including but not limited to letrozole, anastrozole) used continuously for 1 month;
* 2) Gonadotropin-releasing hormone analogs (including but not limited to triptorelin, leuprolide, goserelin) used continuously for 1 month;
* 3) Sex hormones (including but not limited to any type of estrogen, progestin, and androgen) used continuously for 1 month;
* 4) Anabolic steroids (including but not limited to oxymetholone, danazol, stanozolol) used continuously for ≥ 1 month;
* 5) Oral or intravenous corticosteroids used for 1 month.

Primary outcomes:
measure: The change in height standard deviation scores (HT SDS) of the chronological age from baseline.
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
Secondary outcomes:
measure: Annualized Height Velocity
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
measure: The change of height from baseline
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
measure: Bone maturity (bone age/ chronological age , △BA/△CA )
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
measure: The change of IGF-1 standard deviation scores(IGF-1 SDS) from baseline
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
measure: The change of mole ratio of IGF-1/IGFBP-3 from baseline
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
measure: The change of BMI standard deviation scores(BMI SDS)
timeFrame: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
Other outcomes:
Locations:
city: BeiJing
country: China
facility: Children's Hospital, Capital Institute of Pediatrics
state: Beijing
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
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: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Children's Hospital/Shanxi Women and Children Hospital
state: Shanxi
Study officials:
affiliation: Tongji Hospital
name: Xiaoping Luo, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: