Main
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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:
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EUCTR |
Last refreshed on:
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30 March 2020 |
Main ID: |
EUCTR2016-001145-11-DE |
Date of registration:
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14/12/2016 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A trial of TransCon hGH, a sustained-release recombinant human growth hormone product, for treatment of Growth Hormone Deficiency in prepubertal children
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Scientific title:
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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:
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12/02/2018 |
Target sample size:
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150 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001145-11 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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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
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Armenia
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Australia
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Azerbaijan
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Belarus
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Brazil
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Bulgaria
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Canada
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Chile
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Egypt
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France
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Georgia
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Germany
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Greece
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Italy
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Jordan
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Kazakhstan
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Kyrgyzstan
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Lebanon
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Lithuania
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New Zealand
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Poland
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Romania
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Russian Federation
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South Africa
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Spain
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Sweden
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Turkey
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Ukraine
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United Kingdom
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United States
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Contacts
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Name:
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Clinical Trial Information Desk
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Address:
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Tuborg Boulevard 5
2900
Hellerup
Denmark |
Telephone:
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+4570 22 22 44 |
Email:
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clinhelpdesk@ascendispharma.com |
Affiliation:
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Ascendis Pharma A/S |
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Name:
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Clinical Trial Information Desk
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Address:
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Tuborg Boulevard 5
2900
Hellerup
Denmark |
Telephone:
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+4570 22 22 44 |
Email:
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clinhelpdesk@ascendispharma.com |
Affiliation:
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Ascendis Pharma A/S |
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Key inclusion & exclusion criteria
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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
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Hormonal diseases [C19]
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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
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Intervention(s)
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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
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Primary Outcome(s)
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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
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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.
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Timepoint(s) of evaluation of this end point: 52 weeks
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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
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Secondary Outcome(s)
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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
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Timepoint(s) of evaluation of this end point: 52 weeks
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Secondary ID(s)
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TransCon_hGH_CT-301
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Source(s) of Monetary Support
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Ascendis Pharma Endocrinology Division A/S
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Ethics review
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Status: Approved
Approval date: 12/02/2018
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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