Norditropin Treatment in Subjects with Noonan Syndrome. Effects on Linear Growth and Final Height - Data Collection and Follow-up Visit

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-000042-37-SE
• Date of registration: 12/04/2005
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: Norditropin Treatment in Subjects with Noonan Syndrome. Effects on Linear Growth and Final Height - Data Collection and Follow-up Visit
• Scientific title: Norditropin Treatment in Subjects with Noonan Syndrome. Effects on Linear Growth and Final Height - Data Collection and Follow-up Visit
• Date of first enrolment: 11/07/2005
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000042-37
• 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: Present trial: Not randomised or controlled; Original trial as above. If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
The present inclusion criteria are
• Informed consent before any trial related activities
• Participation in the original Norditropin® study (S/GHD/004/NOO) or following the protocol for S/GHD/004/NOO without being randomised in the trial
The original inclusion criteria were
• Verbal informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
• Children with Noonan Syndrome. The diagnostic criteria will be

o Short stature
o Hypertelorism
o Low set ears
o And one of the following criteria:
? Ptosis
? Cubiti valga
? Testicular dysplasia
? Hypogonadotroph hypogonadism
• Bone age determination showing no significant acceleration (more than one year above chronological age) according to Greulich and Pyle (14). Patients showing an accelerated bone age (> chronological age) at the first examination will be reevaluated within 6 weeks before treatment start in order to evaluate the development process
• Age at start of the treatment
Age: 3.00-11.99 years
• Prepubertal according to Tanner standards:
< stage 2 with testes < 4 ml (boys) and no breast development (girls)
• Height < -2 SD of the used Swedish National growth standards (15)taranger
• Height velocity below 1 SD during the 12 months pre-treatment period (15)
• Normal thyroid function
• Normal karyotype
• Available height data since birth
• Parent heights available
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
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:
The original exclusion criteria were
• Earlier or ongoing treatment with growth hormone, anabolic steroids or corticosteroids
• Subjects with congenital heart defect perceived to possibly have a major impact on growth
• History of or actual endocrine, metabolic or other serious chronic disease perceived to possibly have a major impact on growth
• Fasting blood glucose consistently above 6.7 mmol/l
• Growth hormone deficiency defined as
o GH levels below 10 µg/l during two consecutive GH stimulation tests



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

Health Condition(s) or Problem(s) studied

Noonan syndrome associated short stature
MedDRA version: 7.1 Level: PT Classification code 10029748

Intervention(s)

Trade Name: Norditropin 24 IU
Product Name: Norditropin 24 IU
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Somatropin
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 24-

Trade Name: Norditropin SimpleXx
Product Name: Norditropin SimpleXx
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Somatropin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3,3-
INN or Proposed INN: Somatropin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6,7-
INN or Proposed INN: Somatropin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: The primary objective is to evaluate the effect of Norditropin® on final height in children with Noonan syndrome

Primary end point(s): Primary Endpoint:
Change in height SDS from start of treatment to final height (referenced to normal population)

Secondary Endpoints:
Efficacy
• Final height SDS (referenced to normal population and Noonan population, respectively)
• Change in height SDS from start of treatment to final height (referenced to Noonan population)
• Height velocity
• Change in height velocity from start of treatment
• Sitting height
• Number and proportion of subjects with final height SDS above -2 SDS
Safety
• Adverse events (AEs)
• HbA1c, Free Thyroxin and TSH
• Fasting blood glucose and insulin
• Haematology, serum biochemistry and urinalysis laboratory variables
• Physical examinations, BP and pulse
• Bone age
• ECG
• Echocardiography
• IGF-I, and IGFBP-3 levels and SDS
• PqCT for assessment of bone mineral status
• DXA scan for assessment of body composition and bone mineral status
• Plasma leptin, ghrelin and adiponectin for assessment of these growth hormone dependent hormones

Secondary Objective: -

Secondary ID(s)

GHNOO-1658