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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21 December 2021 |
Main ID: |
EUCTR2016-001145-11-IT |
Date of registration:
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10/01/2017 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public 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)
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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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07/04/2017 |
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: o Boys: 3-12 years, inclusive o Girls: 3-11 years, inclusive 2) Impaired height (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 3) BMI within ±2.0 SD of the mean BMI for chronological age and sex according to 2000 CDC standards 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 6 months prior to Screening can be accepted to replace 1 or both GH stimulation tests. The highest GH level determines eligibility. 5) Bone age (BA) at least 6 months less than chronological age (X-ray may have been taken within 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 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 (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 6 months prior to Screening may be accepted) 4) Children born small for gestational age (SGA) (ie, birth weight and/or birth length) =-2.0 SD for gestational age 5) Malnutrition, defined as: o Serum albumin level below the lower limit of normal (LLN) according to the reference ranges of the central laboratory, and o Serum iron below the lower limit of normal (LLN) according to the reference ranges of the central laboratory, and o 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 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 (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: 19.1
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 CT-301 (ACP-011) - 12,1mg Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: TransCon hGH (ACP-011) Current Sponsor code: TransCon hGH (ACP-011) Other descriptive name: 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: Sterile Water for Injection Pharmaceutical Form: Solution for injection in pre-fill
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Primary Outcome(s)
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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 Objective: Secondary: • To evaluate the safety of weekly TransCon hGH administered over 52 weeks compared to daily hGH • To evaluate and compare the annualized height velocity 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 the change in serum IGF-1 and IGFBP-3 and the change in 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 PK/PD profile of TransCon hGH, hGH, IGF-1, IGF-1 SDS, IGFBP-3, IGFBP-3 SDS and PEG administered as a weekly injection (PK/PD subset; TransCon hGH cohort only) • To compare the Cmax for hGH of TransCon hGH to the anticipated Cmax of daily hGH • To determine the incidence of anti-hGH antibodies for both treatments, andtreatment emergent anti-PEG antibodies for TransCon hGH over 52 weeks
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Main Objective: To evaluate and compare the annualized height velocity of prepubertal children with growth failure due to GHD treated with weekly TransCon hGH to that of a commercially available daily hGH formulation at 52 weeks.
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Timepoint(s) of evaluation of this end point: 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 • Change in serum IGF-1 and IGFBP-3 levels and change in 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 • Cmax 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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2016-001145-11-DE
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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: 08/02/2017
Contact:
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