A Multicenter, Phase 2, Randomized, Open Label, Active-controlled, Parallel-group Study Investigating the Safety, Tolerability, and Efficacy of Different Dose Levels of ACP-001 Administered Once Weekly Versus Standard Daily rhGH Replacement Therapy in Pre-pubertal Children With Growth Hormone Deficiency (GHD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 45
- 主要终点
- Cmax of hGH
研究概览
简要总结
A six month study of ACP-001, a long-acting growth hormone product, versus standard human growth hormone therapy. ACP-001 will be given once-a-week, standard human growth hormone (hGH) will be given on a daily basis. The primary aim is to demonstrate safety, pharmacokinetics and pharmacodynamics over a period of six months. A secondary objective is the comparison of height velocity (HV) of the ACP-001 treated groups to the daily hGH treatment group.
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
入排标准
- 年龄范围
- 3 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prepubertal children, Tanner stage 1
- •Diagnosis of GHD, confirmed by two stimulation tests
- •Bone age not greater than chronological age
- •Impaired height and height velocity
- •BMI within +/- 2 SD (standard deviations)
- •Baseline IGF-1 (insulin-like growth factor)
- •Normal fundoscopy
- •Stable hormonal replacement therapy (other than hGH)
- •Written Informed Consent
排除标准
- •Prior exposure to rhGH or IGF-I
- •Past or present intracranial tumor; history or presence of malignant disease
- •Small for gestational age (SGA)
- •Malnutrition
- •Psychosocial dwarfism
- •Coeliac disease
- •Anti-hGH antibodies
- •Diabetes mellitus
- •Chromosomal abnormalities (e.g. Turner syndrome, SHOX)
- •Closed epiphyses
- •Known or suspected HIV infection
研究组 & 干预措施
ACP-001, dose-level 2
Once weekly subcutaneous injection of ACP-001
干预措施: ACP-001 (Drug)
ACP-001, dose-level 3
Once weekly subcutaneous injection of ACP-001
干预措施: ACP-001 (Drug)
ACP-001, dose-level 1
Once weekly subcutaneous injection of ACP-001
干预措施: ACP-001 (Drug)
Human Growth Hormone
Once daily subcutaneous injection of human Growth Hormone (rhGH)
干预措施: Human Growth Hormone (Drug)
结局指标
主要结局
Cmax of hGH
时间窗: 0 hours to 168 hours at Visit 3 (Week 13)
As part of the following endpoint: PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the pharmacokinetic (PK) profile of hGH from the daily rhGH groups during visit 1 and 3. Uncorrected Cmax (maximum value of concentration) values at Visit 3 (Week 13)
Incidence of Anti-hGH Binding Antibody Formation
时间窗: Visit 2 - Visit 5
Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Incidence of Anti-hGH Neutralizing Antibody Formation
时间窗: Visit 2 - Visit 5
Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits
Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)
时间窗: Start of study treatment through Visit 5 (Week 27)
Assessment of local tolerability was performed by examining injection sites (by the investigator during study visits) and on the basis of anamnestic data and records in the Patient Diary. Assessments included pain, redness, bruising, swelling, and itching. Every subject was counted only once within each symptom category.
AUC0-168h of hGH
时间窗: 0 hours to 168 hours at Visit 3 (Week 13)
As part of the following endpoint: PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the PK profile of hGH from the daily rhGH group during Visit 1 and Visit 3 Uncorrected AUC0-168h (area under the curve from 0h to 168h) values at Visit 3 (Week 13)
AUEC0-168h of IGF-1
时间窗: 0 hours to 168 hours at Visit 3 (Week 13)
As part of the following endpoint: PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the rhGH group. Uncorrected AUEC0-168 (area under the efficacy curve from 0h-168h) values at Week 13
E-Trough of IGF-1
时间窗: 0 hours to 168 hours at Visit 3 (Week 13)
As part of the following endpoint: PD profile of serum IGF-1 during Visit 1 and Visit 3 compared between the ACP-001 dose groups and to the daily rhGH group Uncorrected E-Trough (the pre-dose efficacy response) values at Week 13
Emax of IGF-1
时间窗: 0 hours to 168 hours at Visit 3 (Week 13)
As part of the following endpoint: PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the daily rhGH group
次要结局
- Annualized Height Velocity(Baseline to 6 months (Visit 5))