A study of ACP-001, a long-acting human growth hormone product, for treatment of Growth Hormone Deficiency in pre-pubertal children

• Register: EUCTR
• Last refreshed on: 19 October 2015
• Main ID: EUCTR2012-002787-27-BG
• Date of registration: 03/06/2013
• Prospective Registration: Yes
• Primary sponsor: Ascendis Pharma A/S
• Public title: A study of ACP-001, a long-acting human growth hormone product, for treatment of Growth Hormone Deficiency in pre-pubertal children
• Scientific title: 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)
• Date of first enrolment: 11/09/2013
• Target sample size: 52
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002787-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Armenia, Belarus, Bulgaria, Czech Republic, Egypt, France, Germany, Greece, Hungary, Poland, Romania, Russian Federation, Slovenia, Turkey, Ukraine

Contacts

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

Key inclusion & exclusion 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:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Growth Hormone Deficiency (GHD) in pre-pubertal children
MedDRA version: 18.1 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

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: Transiently PEGylated hGH prodrug
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10.0-

Trade Name: Genotropin
Product Name: Recombinant human Growth Hormone (rhGH)
Product Code: n/a
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: SOMATROPIN
CAS Number: 12629-01-5
Other descriptive name: recombinant DNA-derived human growth hormone
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5.3-

Primary Outcome(s)

Main Objective: To compare the safety and PK/PD profile of three different ACP-001 doses to that of a commercially available standard daily rhGH formulation in pre-pubertal children with growth failure due to GHD.

Secondary Objective: 1.To evaluate the 6-month growth pattern (height velocity)
2.To select a safe and efficacious dose for pivotal development

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 with ACP-001 at the end of 6 months;
•Change in HT SDS during treatment with ACP-001 at 3 and 6 months compared to baseline;
•Change in serum IGF-I levels during treatment with ACP-001, from baseline to end of 6 months for each ACP-001 dose 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;
•Change in hGH levels during treatment with ACP-001, from baseline to end of 6 months.

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.

Secondary Outcome(s)

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

Secondary ID(s)

ACP-001_CT-004

2012-002787-27-HU

Source(s) of Monetary Support

Ascendis Pharma A/S