Recombinant Human Insulin-like Growth Factor (rhIGF-1) and Growth Hormone (rhGH) Combination Therapy of Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency and Poor Response to First Year of Growth Hormone Therapy: A Phase II, Prospective, Randomized, Open-label, Multi-Centre, Parallel Group Add-On Study Comparing a Flexible rhIGF-1 Dose and Fixed rhGH Dose vs. Fixed rhGH Dose Therapy.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-020742-10-GB
• Date of registration: 04/11/2010
• Prospective Registration: Yes
• Primary sponsor: Ipsen Pharma
• Public title: Recombinant Human Insulin-like Growth Factor (rhIGF-1) and Growth Hormone (rhGH) Combination Therapy of Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency and Poor Response to First Year of Growth Hormone Therapy: A Phase II, Prospective, Randomized, Open-label, Multi-Centre, Parallel Group Add-On Study Comparing a Flexible rhIGF-1 Dose and Fixed rhGH Dose vs. Fixed rhGH Dose Therapy.
• Scientific title: Recombinant Human Insulin-like Growth Factor (rhIGF-1) and Growth Hormone (rhGH) Combination Therapy of Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency and Poor Response to First Year of Growth Hormone Therapy: A Phase II, Prospective, Randomized, Open-label, Multi-Centre, Parallel Group Add-On Study Comparing a Flexible rhIGF-1 Dose and Fixed rhGH Dose vs. Fixed rhGH Dose Therapy.
• Date of first enrolment: 09/05/2011
• Target sample size: 63
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020742-10
• 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: yes Other trial design description: Prospective and multi-centre If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Finland, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Treatment with rhGH at a minimum starting dose of 0.025 mg/kg/day (without dose reduction) to a maximum dose of 0.035 mg/kg/day for at least 12 months and a maximum of 18 months based on the diagnosis of IGHD with a pre-treatment GH stimulation test/spontaneous maximum of GH < 10µg/L
• First year of rhGH treatment resulting in height gain < 0.5 SDS
• Chronological age from 3 to 9 years inclusive for girls, from 3 to 10 years inclusive for boys
• Pre-pubertal: Tanner stage 1 (Girls: Tanner B1, Boys: Testis = 3ml)
• Parent(s)/guardian(s) have provided written informed consent
Are the trial subjects under 18? yes
Number of subjects for this age range:
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:
• Evidence (more than 20% rhGH injections missed) or suspicion of poor compliance during the first year of rhGH treatment
• Hypothalamic-pituitary tumours diagnosed or treated prior to screening
• Evidence of any active malignancy or intracranial tumours
• Co-morbidity known to affect linear growth including, but not limited to, skeletal dysplasia
• Chronic illness including but not limited to diabetes, inborn errors of metabolism, osteochondrodystrophy, disorders of genitourinary, cardiopulmonary, gastrointestinal, or central nervous system
• Any named syndrome known to be associated with short stature but not limited to Prader-Willi syndrome, Russel Silver syndrome, etc.
• Neurological disease and mental disabilities that may interfere with compliance [Attention Deficit Hyperactivity Disorders (ADHD), autism, Asperger]
• Ongoing drug treatment known to alter growth, including but not limited to high dose glucocorticoids
• Multiple hormonal deficiencies except hypothyroidism if corrected and well controlled
• Abnormal findings at previous fundoscopy or echocardiogram
• Significant abnormality in clinical screening laboratories, as determined by the Investigator
• Syndromes that predispose the subject to cancer (e.g. Fanconi syndrome, Bloom syndrome, ataxia telangectasia)
• Active seizure disorders, defined as one or more seizures per month irrespective of anticonvulsant therapy
• Known allergy or hypersensitivity to any components of NutropinAq® (somatropin) or Increlex® (mecasermin)
• Acute critical illness due to complications following open heart or abdominal surgery, multiple accidental traumas or acute respiratory failure
• Any current or previous exposure to therapeutic spinal irradiation
• Prior bone marrow transplantation
• Evidence of clinical malnutrition or growth deficit attributable to emotional deprivation
• Participation in a clinical trial within the last 12 weeks
• Any social or medical condition that, in the opinion of the Investigator, would be detrimental to either the subject or the study


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

Health Condition(s) or Problem(s) studied

Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency
MedDRA version: 12.1 Level: LLT Classification code 10056438 Term: Growth hormone deficiency

Intervention(s)

Trade Name: NutropinAq 10 mg/2 ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Somatropin
CAS Number: 12629-01-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: INCRELEX 10 mg/ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Mecasermin
CAS Number: 67763-96-6
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: NutropinAq 10 mg/2 ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Somatropin
CAS Number: 12629-01-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: To demonstrate a superior efficacy on height velocity (HV) of treatment with a combination of flexible rhIGF-1 dose and 0.035 mg/kg/day of rhGH, as compared to treatment with 0.035 mg/kg/day of rhGH only, after one year of treatment in pre-pubertal children with IGHD, showing a poor response to rhGH treatment during the first treatment year.

Secondary Objective: • To assess:
- effect on HV, delta height SDS, HV SDS of flexible rhIGF-1 dose and fixed rhGH dose combination therapy vs. fixed rhGH dose therapy
- safety of flexible rhIGF-1 dose and fixed rhGH dose combination vs. fixed rhGH dose therapy
- effect on serum concentrations of GH and IGF-1 and their binding proteins during flexible rhIGF-1 dose and fixed rhGH dose combination therapy vs. fixed rhGH dose therapy
- effect on serum concentrations of IGF-1 SDS during flexible rhIGF-1 dose and fixed rhGH dose combination therapy vs. fixed rhGH dose therapy at each visit
- effect on pubertal status
- change in bone age
• To identify prognostic factors of therapeutic response to flexible rhIGF-1 dose and fixed rhGH combination therapy, based on historical data (pre rhGH treatment and at study start), on GH stimulation tests, IGF-1, auxology and diagnosis
• To assess changes in metabolic parameters

Primary end point(s): Difference in mean HV between the two treatment groups after 1 year of treatment. A difference of = 1.5 cm/year is considered to be clinically relevant.

Secondary ID(s)

8-79-52800-011