Clinical study to compare recombinant human growth hormone Cristalia (r-hGH Cristalia) versus Genotropin® in prepubertal children with growth deficiency due to deficiency of growth hormone.

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2016-000446-56-Outside-EU/EEA
• Date of registration: 07/03/2016
• Prospective Registration: Yes
• Primary sponsor: Cristália Produtos Químicos Farmacêuticos Ltda.
• Public title: Clinical study to compare recombinant human growth hormone Cristalia (r-hGH Cristalia) versus Genotropin® in prepubertal children with growth deficiency due to deficiency of growth hormone.
• Scientific title: Clinical study to compare recombinant human growth hormone Cristalia (r-hGH Cristalia) versus Genotropin® in prepubertal children with growth deficiency due to deficiency of growth hormone. - CERES
• Target sample size: 94
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000446-56
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Brazil

Contacts

• Name: Débora Garcia Rodrigues
• Affiliation: Cristália Produtos Químicos Farmacêuticos Ltda.

• Name: Débora Garcia Rodrigues
• Affiliation: Cristália Produtos Químicos Farmacêuticos Ltda.

Key inclusion & exclusion criteria

Inclusion criteria:
Children aged 4 years and 13 years (for girls) and 14 years (for boys);
Children prepubertal (Tanner stage 1); Bone age less than 11 years (for
boys) and 9 years (for girls), documented by radiographs of the hand
and wrist (will accept a radiograph performed within 6 months prior to
enrollment in the study); Naïve children with growth hormone; Children
diagnosed with disturbance in growth due to deficiency of growth
hormone documented before initial treatment with r-hGH through: The
height z score <-2.0 SD for age and sex; A response to a test stimulus
GH release with peak blood 7 ng / ml in the presence of abnormalities
morphostructural hypothalamic-pituitary region shown by Nuclear
Magnetic Resonance (NMR) or; response to stimulus two tests of GH
release with peak 7 ng / ml in the presence of a normal NMR
(stimulating agents are acceptable insulin, clonidine, glucagon,
arginine and L-dopa). Historical values of GH in blood up to 12 months
prior to enrollment in the study will be acceptable. An MRI performed
up to 2 years before inclusion in the study is acceptable; History of
growth velocity below the mean for the normal population for at least 6
months prior to inclusion in the study, according to the table of VC
Tanner (must be historical height data with a minimum of 6 months
and maximum of 18 months. Researcher must ensure that the
measurements were performed in a standardized way in standard
stadiometer (rigid deck and rigid ruler); Baseline IGF-I -0.5 SD for age
and sex (results provided by the central laboratory).
Are the trial subjects under 18? yes
Number of subjects for this age range: 94
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:
Children aged <4 years; Children with clinical signs of puberty (breast
/ genitalia and pubic hair Tanner stage 2); Note: Children who enterpuberty during treatment (breast development Tanner 2 / or testicles 4
ml or 2.5 cm in greatest diameter) shall be excluded; Other causes of
disorder in children including growth in stature for gestational age
(SGA), Turner syndrome, Prader-Willi syndrome, other causes; Children
with closed epiphyses bone; Children with physical changes that
prevent accurate measurement of height; Children with comorbidities
that prevent normal growth. Patients with central hypothyroidism may
be included, if well controlled with l-thyroxine, evidenced by normal
free T4 dosages; dysmorphic syndrome; Presence of signs of skeletal
dysplasia; Evidence of active malignancy or with less than two years of
treatment considered curative; uncontrolled growth of benign
intracranial tumors; Children with benign intracranial hypertension;
Children with clinical evidence of malnutrition considered relevant to
the discretion of the investigator; Children with Diabetes mellitus type
1 or 2; severe acute disease, including complications after heart
surgery by thoracotomy, abdominal surgery, multiple accidental trauma
or acute respiratory failure; concomitant chronic disease which may
interfere with the analysis of the study (eg, hyperthyroidism /
uncontrolled hypothyroidism, gastrointestinal diseases, cardiorespiratory
diseases, liver failure, kidney failure, bone pathologies that
can affect the growth, chronic inflammatory diseases and inborn errors
of metabolism); Patients with hormone deficiency related diseases by
panhypopituitarism may be included if properly controlled; MRI
findings that may interfere with the study drug (examples: intracranial
hypertension, tumors in the hypothalamic-pituitary region); Children
with anti-GH antibodies;
Children undergoing treatment for the disorder or attention deficit
hyperactivity disorder deficit hyperactivity disorder; Concomitant
medication that could influence the secretion of growth (eg, estrogen,
androgen, anabolic steroids, steroids, aromatase inhibitors) hormone.
Physiological doses of corticosteroids for the treatment of pituitary
deficiency are allowed as well as low-dose inhaled and / or nasal
steroids for the treatment of asthma or chronic rhinitis (500mcg or less
/ day beclomethasone or equivalent); or known allergy to the study
medications, or any of the excipients or thinner / solvent
hypersensitivity; Participation in another clinical study within 3 months
before study entry; Statement of legal limitation disability or parent /
legal representative


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

Health Condition(s) or Problem(s) studied

Growth deficiency due to growth hormone deficiency
MedDRA version: 18.1 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: NA
Product Code: NA
Pharmaceutical Form: Lyophilisate and solvent for suspension for injection
INN or Proposed INN: NA
CAS Number: 12629015
Current Sponsor code: CRT076
Other descriptive name: SOMATROPIN
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 16-

Trade Name: Genotropin
Product Name: Genotropin
Pharmaceutical Form: Lyophilisate and solvent for suspension for injection
INN or Proposed INN: NA
CAS Number: 12629015
Current Sponsor code: CRT076
Other descriptive name: SOMATROPIN
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 16-

Primary Outcome(s)

Main Objective: This study aims to evaluate the efficacy of recombinant human growth
hormone Cristália (r-hGH Cristália) compared to Genotropin® after 12
months of treatment, as measured by growth rate (VC) in prepubertal
children with the disorder growth due to deficiency of growth hormone
treatment-naive.

Secondary Objective: Z score variation in height (z-score of height after 12 months of
treatment - z score high at the start of treatment);
Evaluation of immunogenicity of r-hGH periodic quantification of anti-
GH antibodies during the study;
IGF-1 and IGFBP-3 assessment baseline and periodic serum during the
study;
glucose and insulin assessment of baseline and periodic serum fasting
during the study;
Evaluation of the incidence of adverse events during the study;

Timepoint(s) of evaluation of this end point: After 12 months of treatment

Primary end point(s): The primary efficacy endpoint is the difference in growth rate (cm /
year) between the r-hGH group and Cristália Genotropin® group after
12 months of treatment.
The height is measured in millimeters using a stable estadiometer
through a standard procedure, done equally in all research centers.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: After 12 months of treatment

Secondary end point(s): Difference in height variation, expressed by the variation in z score in
height between the r-hGH-Cristália group and the Genotropin® group
after 12 months of treatment.
The Z score variation in height will be calculated as the difference
between the height z score obtained after 12 months of treatment and
the z-score of height obtained at the beginning of the treatment
period.
The Z score of height is the ratio of the actual height minus the
average population height for age and sex divided by the standard
deviation. The Z score calculation must be performed using the growth
curve of the World Health Organization in 2007 to be provided in the
study material. The investigator, or person designated by him / her
should check the expected height and standard deviation for age and
sex of research participants. All this information must be recorded in
the source documents of the research participant
The height is measured in millimeters using a stable estadiometer
through a standard procedure, done equally in all sites.

Secondary ID(s)

CRT076

Source(s) of Monetary Support

Cristália Produtos Químicos Farmacêuticos Ltda.