Growth Hormone Deficiency (GHD) in pre-pubertal children MedDRA version: 17.1 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Name: ACP-001
Product Code: ACP-001
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: somatropin
Current Sponsor code: TransCon PEG hGH
Other descriptive name: Transi
Sponsors
Ascendis Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pre-pubertal children with GHD (either isolated or as part of a multiple pituitary hormone deficiency) in Tanner stage I aged: a. Boys: 3 years = boy’s age = 12 years b. Girls: 3 years = girl’s age = 11 years; 2. Diagnosis of GHD confirmed by two different GH provocation tests, defined as a peak GH level of = 10 ng/mL, determined by a central laboratory using a validated assay. One well documented historical test (with properly recorded sampling times and results as well as euthyroid status of the patient) performed within 3 months prior to Screening can be accepted to replace one GH stimulation test analyzed by the central laboratory; 3. Bone age (BA) not greater than the chronological age; 4. Impaired height and height velocity defined as: a. Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age and sex (HT SDS = - 2.0) according to the CDC standards of 2000 b. Height velocity (HV) of at least 1 SD below the mean HV for chronological age and sex (HV SDS = - 1.0) according to the standards of Prader et al. of 1989, whereas the time between 2 height measurements is not less than 6 months; 5. BMI within ±2 SD of the mean BMI for chronological age and sex according to the 2000 CDC standards; 6. Baseline IGF-I level of at least 1 SD below the mean IGF-I level standardized for age and sex (IGF-I SDS = -1.0) according to the central laboratory reference values; 7. Normal fundoscopy at Screening (without signs/symptoms of intracranial hypertension); 8. Children with multiple hormonal deficiencies must be on stable replacement therapy (stable dose and normal blood hormone levels) for other hypothalamo-pituitary axes for at least 3 months. Thyroid replacement therapy for thyroid hormone deficiency must be instituted at least 6 months (and be stable for at least 3 months) prior to Screening. Temporary adjustment of glucocorticoid replacement therapy, as appropriate, is acceptable; 9. Normal 46 XX karyotype for girls; 10. Written informed consent of the parent or legal guardian of the patient and written assent of the patient (if the patient is able to read, understand, and sign). Are the trial subjects under 18? yes Number of subjects for this age range: 52 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Children with a body weight below 11 kg; 2. Children with hematocrit at Screening below 34%; 3. Prior exposure to rhGH or IGF-I therapy; 4. Children with past or present intracranial tumor growth as confirmed by a sellar MRI scan (with contrast) at Screening (if no MRI was performed within the last 6 months prior to Screening); 5. Children born small for gestational age (SGA), i.e. birth weight and/or birth length < -2 SD for gestational age; 6. Malnutrition, defined as: a. Serum albumin level below the lower limit of normal (LLN) according to the reference ranges of the central laboratory, and b. Serum iron below the lower limit of normal (LLN) according to the reference ranges of the central laboratory, and c. BMI < -2 SD for age and sex; 7. Children with psychosocial dwarfism; 8. Children with idiopathic short stature; 9. Other causes of short stature such as coeliac disease (confirmed by anti-transglutaminase antibodies test), hypothyroidism, or rickets; 10. Presence of anti-hGH binding antibodies at Screening; 11. History or presence of malignant disease; any evidence of present tumor growth; 12. Any clinically significant abnormality likely to affect growth or the ability to evaluate growth, e.g. chronic diseases like renal insufficiency, spinal cord irradiation, etc.; 13. Patients with diabetes mellitus or impaired fasting sugar (based on WHO standards); 14. Chromosomal abnormalities and medical syndromes (Turner syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX mutations/deletions and skeletal dysplasias) with the exception of septo-optic dysplasia; 15. Closed epiphyses; 16. Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids or methylphenidate for attention deficit hyperactivity disorder (ADHD) with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin); 17. Children requiring glucocorticoid therapy (e.g. asthma) who are taking a dose of greater than 400 µg/d of inhaled budesonide or equivalents for longer than 1 month during a calendar year; 18. Major medical conditions and/or presence of contraindication to rhGH treatment; 19. Known or suspected HIV-positive patient; 20. Known hypersensitivity to the components of the study medication; 21. The patient and/or the parent/legal guardian are likely to be noncompliant in respect to study conduct; 22. Participation in any other trial of an investigational agent within 30 days prior to Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety endpoints •Incidence of AEs; •Local tolerability (assessed by the patient and the investigator); •Incidence of anti-hGH antibody and incidence of treatment-emergent anti-PEG antibody formation; •IGF-I levels; •Parameters of glucose metabolism (fasting glucose and insulin level, HbA1c) and lipid parameters; •Hormone levels: thyroid status and cortisol levels; •All other hematology and biochemistry blood parameters; •Results of the physical examinations, vital sign measurements and ECG. Efficacy endpoints •The relationship between the dose of ACP-001 or daily rhGH and the annualized HV at 6 months; •Relationship between delta HT SDS and ACP-001 dose or daily rhGH dose after 3 and 6 months of treatment; •Annualized HV during treatment with ACP-001 at the end of 6 months, for each ACP-001 dose group and for the daily rhGH treatment group; •Comparison of annualized height velocity between ACP-001 and the corresponding dose of daily rhGH; •Change in HT SDS during treatment with ACP-001 at 3 and 6 months compared to baseline for each ACP-001 dose groups and for the daily rhGH treatment group; •Change in serum IGF-I levels during treatment with ACP-001, from baseline to end of 6 months for each ACP-001 dose group, compared between the ACP-001 dose groups and to the daily rhGH group; •IGF-I standard deviation scores (IGF-I SDS) and proportion of patients achieving normalization of serum IGF-I levels during treatment with ACP-001 (for each dose regimen) or daily rhGH, including comparisons between treatment groups; •Change in hGH levels during treatment with ACP-001, from baseline to end of 6 months compared between the ACP-001 dose groups and to the daily rhGH group.;Timepoint(s) of evaluation of this end point: •The relationship between the dose of ACP-001 or daily rhGH and the annualized HV at 6 months; •Relationship between delta HT SDS and ACP-001 dose or daily rhGH dose after 3 and 6 months of treatment; •Annualized HV during treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PK and PD endpoints •PK profile of 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 V1 and V3; •PK profile of TransCon PEG hGH during V1 and V3 (ACP-001 treated patients only); •PK profile of PEG during V1 and V3 (ACP-001 treated patients only); •PD profile of IGF-I and IGFBP-3 during V1 and V3 compared between the ACP-001 dose groups and to the daily rhGH group.;Timepoint(s) of evaluation of this end point: All PK and PD endpoints will be evaluated during visits V1 and V3 | — |
Countries
Belarus, Bulgaria, Czech Republic, Egypt, France, Germany, Greece, Hungary, Poland, Romania, Russian Federation, Slovenia, Turkey, Ukraine
Contacts
Public ContactClinical Trials Info
Accelsiors CRO and Consultancy Services Ltd
Outcome results
None listed