A Randomized, Multicenter, Active-controlled Openlabelled, Multiple-Dose, Dose Finding, Parallel Group Trial, Investigating the Efficacy, Safety, Immunogenicity, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Different Weekly Doses of ALT-P1 Compared to Daily Growth Hormone Treatment of GENOTROPIN® (Somatropin) for Injection in Growth Hormone Treatment naive Prepubertal Children with Growth Hormone Deficiency.
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 14
- 主要终点
- Efficacy Endpoint:
研究概览
简要总结
This is a randomized, multicenter, active-controlled open labelled, multiple-dose, dose finding, and parallel group trial dosing 60 boys or girls subjects with growth hormone deficiency for 29 weeks. There are 4 arms in the study.
Arm 1: ALT-P1 dose-level 1 (0.4 mg/kg/week)
Arm 2: ALT-P1 dose-level 2 (0.6 mg/kg/week)
Arm 3: ALT-P1 dose-level 3 (0.8 mg/kg/week)
Arm 4: GENOTROPIN® (Somatropin) (0.24 mg/kg/week or 0.034 mg/kg/day) for Injection
Study Duration: Total study duration for the clinical part will be of around 35 weeks including 4 weeks of screening period, 28 weeks of treatment period, 1 week of end of study assessment and 2 weeks of safety follow-up after end of study.
Visit Schedules:
Screening visit / Screening Period (Up to 28 days prior to randomization): Visit 1.
• Randomization visit/ Baseline visit: Visit 2/ Week 1 (Day 1).
• Interim visit: Visit 3 (Week 3/Day 15± 2 days) &, Visit 4 (Week 5/Day 29 ± 2 days)*, Visit 5 (Week 9/Day 57± 2 days), Visit 6 (Week 13/Day 85± 2 days) ¸ Visit 7 (Week 17/Day 113± 2 days), Visit 8 (Week 21/Day 141± 2 days) and Visit 9 (Week 25/Day 169 ± 2 days).
Note: Visit 3 (Week 3/Day 15± 2) will be applicable for Arm 2 and Arm 3 subjects only. Visit 4 (Week 5/Day 29 ± 2 days) will be applicable for all Arms, however dose escalation will be applicable for Arm 3 subjects only.
• End of study#: Visit 10 (Week 29/Day 197+7 days).
• Safety follow-up: 14 days (±7 days) after end of study visit. Subjects may visit the study site or it may be performed telephonically.
Dose and Mode of Administration: Subcutaneous injection.
Test Product (T):
Arm 1: ALT-P1 dose-level 1 (0.4 mg/kg/week)
Arm 2: ALT-P1 dose-level 2 (0.6 mg/kg/week)
Arm 3: ALT-P1 dose-level 3 (0.8 mg/kg/week)
Reference Product (R):
Arm 4: GENOTROPIN® (Somatropin) (0.24 mg/kg/week or 0.034 mg/kg/day) for Injection
Study product will be administered as a s.c. injection once weekly (Week 1/Day 1 to Week 28/Day 190) for Arm 1, 2 and 3 and daily (Day 1 to Day 196) for Arm 4 as per randomization, using the PEN or vial into the upper arm (ALT-P1 only), thigh, buttocks, and abdomen as per randomization schedule.
Dosing will be done at site at Visit 2/ Week 1 (Day 1), Visit 4 (Week 5/Day 29 ± 2 days), Visit 5 (Week 9/Day 57± 2 days), Visit 6 (Week 13/Day 85± 2 days), Visit 7 (Week 17/Day 113± 2 days), Visit 8 (Week 21/Day 141± 2 days) and Visit 9 (Week 25/Day 169 ± 2 days). Rest of the other dosing will be done at subject’s home by parents/legal guardians.
Dosing will be done at site at Visit 3 (Week 3/Day 15± 2 days) for Arm 2 and Arm 3 subjects only.
The dose administration via PEN or vial will be done by investigator or trained study personnel at site and by parents/legal guardians at home.
PK and PD (IGF-1 and IGFBP-3) Samples collection: During the study, a total of 17 blood samples (7 ml each) will be collected in each Arm 1, 2 and 3 and 11 blood samples (7 ml each) will be collected for Arm 4 for pharmacokinetic and pharmacodynamic analysis.
For Arm 1, 2 and 3: At Week 13/ Day 85: 0, 6, 12, 24, 48, 72, 96, 120, 144 and 168 hours. Post dose blood sample of 48, 72, 96, 120, 144 and 168 hours will be collected as an ambulatory sample.
Note: All pre dose sample will be collected within 01 hour prior to dosing. All post dose samples up to 12 hours will be collected within ± 10 minutes of the scheduled time and from 24 hours, sample will be collected ± 3 hours of the scheduled time. All ambulatory sample will be collected within ± 3 hours of the scheduled time.
For Arm 4:
Week 13/Day 85: 0, 6, 12, 24 hours.
Pre dose sample will be collected within 01 hour prior to dosing.
For All Arms:
PK/PD sample will be collected at Visit 2 (Week 1/Day 1), Visit 4 (Week 5/Day 29 ± 2 days), Visit 5 (Week 9/Day 57± 2 days), Visit 7 (Week 17/Day 113± 2 days), Visit 8 (Week 21/Day 141± 2 days), Visit 9 (Week 25/Day 169 ± 2 days) prior to dosing.
PK/PD sample at Visit 10 (Week 29/Day 197+7 days) will be collected during end of study assessment.
Housing Details: Housing from at least 2 hours before dosing to at least 24 hours post dose of Week 13/Day 85. Subject will be instructed to visit the clinical site for 48, 72, 96, 120, 144 and 168 hours post dose of Week 13 blood sample on the ambulatory basis except Arm 4 subjects.
Food and Fluid Restrictions: Food and fluid instruction needs to be followed as per protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- None
入排标准
- 年龄范围
- 2.00 Year(s) 至 11.00 Year(s)（—）
- 性别
- All
入选标准
- •Age: For boys: age at least 2 years and 26 weeks and below or equal to 11.0 years at screening.
- •For girls: age at least 2 years and 26 weeks and below or equal to 10.0 years at screening.
- •Boys: Tanner stage 1 for pubic hair and testis volume below 4 ml, age at least 2 years and 26 weeks and below or equal to 11.0 years at screening Or Girls: Tanner stage 1 for breast development (no palpable glandular breast tissue) and pubic hair, age at least 2 years and 26 weeks and below or equal to 10.0 years at screening.
- •Confirmed diagnosis of growth hormone deficiency (GHD) within 12 months prior to screening as determined by two different growth hormone (GH) stimulation tests (any two tests from clonidine, insulin, glucagon, arginine and GHRH), defined as a peak GH level of below or equal to 7.0 ng/ml.
- •For children with three or more pituitary hormone deficiencies only one GH stimulation test is needed.
- •No prior exposure to GH therapy and/or insulin-like growth factor-1(IGF-1) treatment.
- •Bone age not greater than chronological age (CA) at the time of screening (on the basis of x-rays of the left hand and wrist).
- •Impaired height and Height Velocity at the time of screening.
- •Impaired height defined as: Height of at least 2.0 standard deviations below the mean height for CA and gender according to the standards of WHO 2006 & Indian academy of pediatrics (IAP) 2015 combined Girls/Boys charts 0-18 years: Girls/Boys stature-for-age and weight-for-age percentiles at screening.
- •Impaired height velocity defined as: Annualized height velocity (HV) below the 25th percentile for CA and gender or below -0.7 standard deviation (SD) score for CA and sex, according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months.
- •Body mass index (BMI) within ±2 standard deviation at the time of screening for the chronological age and sex according to the 2000 Centers for Disease Control and Prevention standards.
- •IGF-1 level of at least 1 standard deviation below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1) according to the central laboratory reference values at the time of screening.
- •Children with normal report of fundoscopy at the time of screening.
- •Parent or legal guardian of the child must be willing and able to provide written informed consent and oral assent from child aged between 7 to11 (both inclusive).
排除标准
- •Children will not be eligible for inclusion in this study if any of the following criteria apply:
- •Children born small for gestational age (SGA) (SGA – birth weight and/or birth length less than -2 SDS for gestational age).
- •Malnourished children defined as BMI less than -2 SDS for age and sex at the time of screening.
- •Serum albumin and iron below the lower limit of normal (LLN) according to the central laboratory at the time of screening.
- •Presence of anti-hGH antibodies at screening.
- •Children with other cause of short stature such as hypothyroidism or coeliac disease or rickets.
- •Children with more than 1 closed epiphyses at the time of screening.
- •Note: Evaluation will be performed based on physical examination as per judgment of Investigator and if required additional radiological investigation can be performed.
- •Presence or history of intracranial tumor and intracranial hypertension.
- •Presence or history of any malignant disease.
- •Children with Psychosocial dwarfism.
- •Children with impaired fasting sugar (fasting blood sugar greater than 100 mg/dL or 5.6 mmol/L) at the time of screening.
- •Children with chromosomal abnormalities and medical symptoms including Turner’s syndrome, Noonan syndrome, Prader-Willi syndrome and SHOX mutations/deletions, Laron syndrome, Russell- Silver syndrome and skeletal dysmorphic/dysplasia at the time of screening.
- •Children with known serum positivity for Hepatitis B, C or HIV at the time of screening.
- •History of Tuberculosis.
- •History of drug dependence in the past 1 year prior to screening.
- •Known hypersensitivity to the components of study medication.
- •Participation in any other trial of an investigational agent within 30 days prior to screening.
- •Any clinically significant abnormality apart from growth hormone, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, etc.
- •Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, glucocorticoids and methylphenidate for attention deficit hyperactivity disorder (ADHD), with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin (DDAVP)).
- •Children requiring glucocorticoid therapy (e.g. for asthma) that are taking chronically a dose greater than 400 μg/day of inhaled budesonide or equivalent as for more than 1 month during the 12 months prior to Visit
- •Presence of contraindications to hGH treatment (Refer prescribing Information of GENOTROPIN7).
- •Females of child-bearing potential Although children’s who are of child-bearing potential at the time of enrollment will be exclusionary, children who begin menses during the trial may continue.
- •The children and/or the parent/legal guardian are likely to be noncompliant in respect to study conduct.
结局指标
主要结局
Efficacy Endpoint:
时间窗: 29 Weeks
a. Annualized height velocity at Week 29 (absolute and SDS).
时间窗: 29 Weeks
次要结局
- 1. Safety endpoints:(a. Number of subjects reporting local tolerability events (Patient and Investigator assessment).)
研究者
Dr Dharmesh Domadia
Cliantha Research Limited