World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 30 March 2020
Main ID:  EUCTR2016-001145-11-DE
Date of registration: 14/12/2016
Prospective Registration: Yes
Primary sponsor: Ascendis Pharma Endocrinology Division A/S
Public title: A trial of TransCon hGH, a sustained-release recombinant human growth hormone product, for treatment of Growth Hormone Deficiency in prepubertal children
Scientific title: A multicenter, Phase 3, randomized, open-label, active-controlled, parallel-group trial investigating the safety, tolerability, and efficacy of TransCon hGH administered once a week versus standard daily hGH replacement therapy over 52 weeks in prepubertal children with growth hormone deficiency (GHD)
Date of first enrolment: 12/02/2018
Target sample size: 150
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001145-11
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: yes Other specify the comparator: Genotropin (somatropin [rDNA origin] Powder and Solvent for Solution for Injection Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Armenia Australia Azerbaijan Belarus Brazil Bulgaria Canada Chile
Egypt France Georgia Germany Greece Italy Jordan Kazakhstan
Kyrgyzstan Lebanon Lithuania New Zealand Poland Romania Russian Federation South Africa
Spain Sweden Turkey Ukraine United Kingdom United States
Contacts
Name: Clinical Trial Information Desk   
Address:  Tuborg Boulevard 5 2900 Hellerup Denmark
Telephone: +4570 22 22 44
Email: clinhelpdesk@ascendispharma.com
Affiliation:  Ascendis Pharma A/S
Name: Clinical Trial Information Desk   
Address:  Tuborg Boulevard 5 2900 Hellerup Denmark
Telephone: +4570 22 22 44
Email: clinhelpdesk@ascendispharma.com
Affiliation:  Ascendis Pharma A/S
Key inclusion & exclusion criteria
Inclusion criteria:
1) Prepubertal children with GHD (either isolated or as part of a multiple pituitary hormone deficiency) in Tanner stage 1 aged:
• Boys: 3-12 years, inclusive
• Girls: 3-11 years, inclusive
2) Impaired HT defined as at least 2.0 standard deviations (SD) below the mean height for chronological age and sex
(HT SDS =-2.0) according to the 2000 CDC Growth Charts for the United States Methods and Development or, after approval by the Medical Expert, at least 1.5 SD below the mid-parental height
3) BMI within ±2.0 SD of the mean BMI for chronological age and sex according to 2000 CDC standards, or BMI within ±2.0 SD of the mean BMI for bone age and sex
4) Diagnosis of GHD confirmed by 2 different GH stimulation tests, defined as a peak GH level of =10 ng/mL, determined with a validated assay. One or 2 well documented historical tests (with properly recorded sampling times and results as well as documented euthyroid status of the subject) performed within approximately 6 months prior to Screening can be accepted to replace 1 or both GH stimulation tests. The highest GH level determines eligibility. For subjects with known panhypopituitarism (eg, subjects who are deficient in TSH and/or ACTH post cranial radiation or born with = 2 pituitary hormone deficiencies in addition to GH), GH stimulation tests may not be required.
5) Bone age (BA) at least 6 months less than chronological age (X-ray may have been taken within approximately 6 months prior to Screening, the X-ray or digital image should be sent to the central reader).
6) Baseline IGF-1 level of at least 1.0 SD below the mean IGF-1 level standardized for age and sex (IGF-1 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 approximately
3 months. Thyroid replacement therapy for thyroid hormone deficiency must be instituted approximately 6 months (and be stable for approximately 3 months) prior to Screening. Temporary adjustment of glucocorticoid replacement therapy, as appropriate, is acceptable.
9) Normal 46 XX karyotype for girls (results prior to Screening may be accepted).
10) Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is able to read, understand, and sign).
Are the trial subjects under 18? yes
Number of subjects for this age range: 150
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 12 kg
2) Prior exposure to recombinant hGH or IGF-1 therapy
3) Children with past or present intracranial tumor growth as confirmed by a sellar MRI scan (with contrast dye recommended) at Screening (MRI results from up to approximately 6 months prior to Screening may be accepted)
4) Children born small for gestational age (SGA) (ie, birth weight =-2.0 SD for gestational age, with or without a birth length =-2.0 SD for gestational age)
5) Malnutrition, defined as:
• Serum albumin level below the lower limit of normal (LLN) according to the reference ranges of the central laboratory, and
• Serum iron below the LLN according to the reference ranges of the central laboratory, and
• body mass index (BMI) =-2.0 SD for age and sex
6) Children with psychosocial dwarfism
7) Children with idiopathic short stature
8) Other causes of short stature such as coeliac disease (confirmed by anti-transglutaminase antibodies test), hypothyroidism, or rickets
9) History or presence of malignant disease; any evidence of present tumor growth; children with GHD and clinically cured tumors may be eligible after consultation with the Medical Expert
10) Any clinically significant abnormality likely to affect growth or the ability to evaluate growth (eg, chronic diseases like renal insufficiency, spinal cord irradiation)
11) Subjects with poorly controlled diabetes mellitus (HbA1c =8.0%) or diabetic complications
12) Known chromosomal abnormalities and other named medical syndromes known to impact growth (eg, 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
13) Closed epiphyses
14) Tanner stage >1 (scant pubic hair alone does not exclude the subject)
15) Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin)
16) Children requiring glucocorticoid therapy (eg, 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
(Note: Approximately equivalent doses: fluticasone: 264 µg/d; beclomethasone: 504 µg/d; flunisolide 1,000 µg/d; triamcinolone: 1,000 µg/d; mometasone: 211 µg/d; ciclesonide 264 µg/d)
17) Major medical conditions and/or presence of contraindication to hGH treatment
18) Known or suspected HIV-positive subject
19) Known hypersensitivity to the components of the study drug
20) The subject and/or the parent/legal guardian are likely to be non-compliant with respect to trial conduct
21) Participation in any other trial of an investigational agent within 3 months prior to Screening
22) Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Hormonal diseases [C19]
Growth hormone deficiency (GHD) in prepubertal children
MedDRA version: 20.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders
Intervention(s)

Product Name: TransCon hGH (ACP-011) - 12.1mg
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: lonapegsomatropin
Current Sponsor code: TransCon PEG40 hGH
Other descriptive name: TRANSCON PEG40 HGH, Transiently PEGylated hGH prodrug
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.1-

Trade Name: GENOTROPIN 12 mg powder and solvent for solution for injection.
Product Name: GENOTROPIN 12 mg powder and solvent for solution for injection.
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: 12-

Trade Name: GENOTROPIN 12 mg powder and solvent for solution for injection.
Product Name: GENOTROPIN 12 mg powder and solvent for solution for injection.
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: 12-

Trade Name: GENOTROPIN 12 mg powder and solvent for solution for injection.
Product Name: GENOTROPIN 12 mg powder and solvent for solution for injection.
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: 12-

Product Name: TransCon hGH (ACP-011) - 24.2mg
Pharmaceutical Form: Powder and solvent for sol
Primary Outcome(s)
Secondary Objective: • To evaluate the safety of weekly TransCon hGH administered over 52 weeks compared to daily hGH
• To evaluate and compare the annualized HV over 52 weeks of weekly TransCon hGH to daily hGH
• To evaluate and compare the change in height SDS over 52 weeks of weekly TransCon hGH to daily hGH
• To evaluate serum IGF-1 and IGFBP-3 and IGF-1 SDS and IGFBP-3 SDS; and the normalization of IGF-1 SDS over 52 weeks of weekly TransCon hGH or daily hGH
• To describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of TransCon hGH, hGH, IGF-1, IGF-1 SDS, IGFBP-3, IGFBP-3 SDS and polyethylene glycol (PEG) administered as a weekly injection (PK/PD subset; TransCon hGH cohort only)
• To compare the maximum value of concentration (Cmax) for hGH of TransCon hGH to the anticipated Cmax of daily hGH
• To determine the incidence of anti-hGH antibodies for both treatments, and treatment emergent anti-PEG antibodies for TransCon hGH over 52 weeks
Main Objective: To evaluate and compare the annualized height velocity (HV) of prepubertal children with growth failure due to GHD treated with weekly TransCon hGH to that of a commercially available daily human growth hormone (hGH) formulation at 52 weeks.
Timepoint(s) of evaluation of this end point: 52 weeks
Primary end point(s): Efficacy endpoints:
Primary efficacy endpoint: Annualized HV at 52 weeks for weekly TransCon hGH and daily hGH treatment groups

Safety endpoints:
• Incidence of AEs
• Local tolerability (assessed by the subject, the parents/legal guardians and the
investigator)
• Incidence of anti-hGH antibodies including neutralizing antibodies as needed (both cohorts) and incidence of treatment-emergent anti-PEG antibody formation (in TransCon hGH subjects)
• IGF-1 levels and IGF-1 SDS
• Parameters of glucose metabolism (fasting glucose and insulin level, HbA1c)
and lipid parameters
• Hormone levels: thyroid status and morning cortisol
• All other hematology and biochemistry blood parameters
• ECG
• Results of the physical examinations, vital sign measurements
• Bone age at 52 weeks
Secondary Outcome(s)
Secondary end point(s): Secondary efficacy endpoints:
• Annualized HV for the TransCon hGH and the daily hGH treatment group over 52 weeks
• Change in HT SDS over 52 weeks for the TransCon hGH and the daily hGH treatment group
• Serum IGF-1 and IGFBP-3 levels and IGF-1 SDS and IGFBP-3 SDS; and normalization of IGF-1 SDS over 52 weeks for the TransCon hGH and the daily hGH treatment group

Pharmacokinetic and pharmacodynamic endpoints:
Subset of at least 8 TransCon hGH treated subjects after 13 weeks of treatment:
• PK profile of TransCon hGH over 1 week
• PK profile of hGH over 1 week
• PK profile of PEG over 1 week
• PD profile of IGF-1 and IGFBP-3 over 1 week
• PD profile of IGF-1 SDS and IGFBP-3 SDS over 1 week
• C max for hGH of TransCon hGH
Timepoint(s) of evaluation of this end point: 52 weeks
Secondary ID(s)
TransCon_hGH_CT-301
Source(s) of Monetary Support
Ascendis Pharma Endocrinology Division A/S
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 12/02/2018
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history