A Multicenter, Randomized, Open-Label, Dose-Response, Phase II Clinical Study of Pegylated Somatropin (PEG Somatropin) Injection to Treat SGA Children With Short Stature.
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 96
- 试验地点
- 9
- 主要终点
- The change in height standard deviation scores (HT SDS) of the chronological age from baseline.
研究概览
简要总结
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.
详细描述
This was a multicenter, randomized phase II study, half of participants will receive the high dose, while the other half will receive the low dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None (Participant, Investigator)
入排标准
- 年龄范围
- 3 Years 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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+
- •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.
排除标准
- •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:
- •Aromatase inhibitors (including but not limited to letrozole, anastrozole) used continuously for 1 month;
- •Gonadotropin-releasing hormone analogs (including but not limited to triptorelin, leuprolide, goserelin) used continuously for 1 month;
- •Sex hormones (including but not limited to any type of estrogen, progestin, and androgen) used continuously for 1 month;
- •Anabolic steroids (including but not limited to oxymetholone, danazol, stanozolol) used continuously for ≥ 1 month;
- •Oral or intravenous corticosteroids used for 1 month.
研究组 & 干预措施
PEG-somatropin: Low dose
0.1 mg/(kg.w), once per week for 52 weeks.
干预措施: PEG-somatropin (Biological)
PEG-somatropin: High dose
0.2 mg/(kg.w), once per week for 52 weeks.
干预措施: PEG-somatropin (Biological)
Children who completed the 52- week main phase proceeded to the extension phase
Dose adjustments based on annualized height velocity (AHV; cm/year) 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.
干预措施: PEG-somatropin (Biological)
结局指标
主要结局
The change in height standard deviation scores (HT SDS) of the chronological age from baseline.
时间窗: The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.
次要结局
- Annualized Height Velocity(The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.)
- The change of height from baseline(The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.)
- Bone maturity (bone age/ chronological age , △BA/△CA )(The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.)
- The change of IGF-1 standard deviation scores(IGF-1 SDS) from baseline(The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.)
- The change of mole ratio of IGF-1/IGFBP-3 from baseline(The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.)
- The change of BMI standard deviation scores(BMI SDS)(The main phase is at 52 weeks and the extension phase is at every 52 weeks up to study completion.)