Health Condition 1: E230- Hypopituitarism
Conditions
Interventions
Intervention1: ALT-P1: three different weekly doses of 0.4, 0.6, and 0.8mg/kg/week for (Week 1/Day 1 to Week 28/Day 190)
Control Intervention1: GENOTROPIN�® (Somatropin): Daily dose of 0.24 mg/kg/w
Sponsors
CristÃ?¡lia Produtos QuÃ?Âmicos FarmacÃ?ªuticos Ltda
Cliantha Research Limited
Eligibility
Inclusion criteria
Inclusion criteria: 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. 1. 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. 2. 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. 3. No prior exposure to GH therapy and/or insulin-like growth factor-1(IGF-1) treatment. 4. 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). 5. 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. 6. 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. 7. IGF-1 level of at least 1 standard deviation below the mean IGF-1 level standardized for age and sex (IGF-1 SDS â�¤-1) according to the central laboratory reference values at the time of screening. 8. Children with normal report of fundoscopy at the time of screening. 9. Children with multiple hormonal deficiencies must be on stable replacement therapy (other than hGH) for at least 3 months (or 6 months for thyroid replacement therapy) prior to screening. 10. 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).
Exclusion criteria
Exclusion criteria: Children will not be eligible for inclusion in this study if any of the following criteria apply: 1. Children born small for gestational age (SGA) (SGA ââ?¬â?? birth weight and/or birth length less than -2 SDS for gestational age). 2. 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. 3. Presence of anti-hGH antibodies at screening. 4. Children with other cause of short stature such as hypothyroidism or coeliac disease or rickets. 5. 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. 6. Presence or history of intracranial tumor and intracranial hypertension. 7. Presence or history of any malignant disease. 8. Children with Psychosocial dwarfism. 9. Children with impaired fasting sugar (fasting blood sugar greater than 100 mg/dL or 5.6 mmol/L) at the time of screening. 10. Children with chromosomal abnormalities and medical symptoms including Turnerââ?¬•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. 11. Children with known serum positivity for Hepatitis B, C or HIV at the time of screening. 12. History of Tuberculosis. 13. History of drug dependence in the past 1 year prior to screening. 14. Known hypersensitivity to the components of study medication. 15. Participation in any other trial of an investigational agent within 30 days prior to screening. 16. Any clinically significant abnormality apart from growth hormone, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, etc. 17. 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)). 18. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking chronically a dose greater than 400 Ã?¼g/day of inhaled budesonide or equivalent as for more than 1 month during the 12 months prior to Visit 1. 19. Presence of contraindications to hGH treatment (Refer prescribing Information of GENOTROPIN7). 20. Females of child-bearing potential Although childrenââ?¬•s who are of child-bearing potential at the time of enrollment will be exclusionary, children who begin menses during the trial may continue. 21. The children and/or the parent/legal guardian are likely to be noncompliant in respect to study conduct.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy Endpoint: a. Annualized height velocity at Week 29 (absolute and SDS).Timepoint: 29 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety endpoints: a. Number of subjects reporting local tolerability events (Patient and Investigator assessment). b. Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). 2. Auxology endpoints: a. Change in height, absolute and SDS from baseline to Week 29. b. Change of IGF-1 SDS from baseline to Week 29. 3. Immunogenicity endpoint a. Incidence of Anti-drug antibody (Anti- drug antibody will be further characterized into Binding and Neutralizing antibody). 4. Pharmacokinetic endpoints: a. For ALT-P1 (Time Frame - From 0 to 168 h) Cmax of ALT-P1 AUC0-168h of ALT-P1 b. For r-hGH (Time Frame - From 0 to 24h). Cmax of r-hGH AUC0-24h of r-hGH 5. Pharmacodynamic endpoints a. For ALT-P1 (Time Frame - From 0 to 168 h) Emax of IGF-1, AUC0-168h of IGF-1, Emax of IGFBP-3, AUC0-168h of IGFBP-3 Timepoint: Week 29 | — |
Countries
India
Contacts
Public ContactMr Devesh Verma
Cliantha Research Limited
Outcome results
None listed