A study of MOD-4023 compared with daily GH therapy in children with lack of growth hormone in the body

• Register: EUCTR
• Last refreshed on: 6 February 2017
• Main ID: EUCTR2011-004553-60-HU
• Date of registration: 03/11/2011
• Prospective Registration: Yes
• Primary sponsor: OPKO Biologics Ltd.
• Public title: A study of MOD-4023 compared with daily GH therapy in children with lack of growth hormone in the body
• Scientific title: Safety and dose finding study of different MOD-4023 dose levels compared to daily r-hGH therapy in pre-pubertal growth hormone deficient children
• Date of first enrolment: 10/01/2012
• Target sample size: 56
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004553-60
• 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: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Bulgaria, Czech Republic, Greece, Hungary, Poland, Russian Federation, Slovakia, Ukraine, United States

Contacts

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1.Pre-pubertal child aged = 3 yrs old and not above 10 years for girls or 11 years for boys with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone deficiency.
2. Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak plasma GH level of =10 ng/ml, determined by central laboratory using a validated assay. If the patient has already been tested locally and reserve samples that were taken at appropriate time-points are available, these will be reanalyzed by the central laboratory. Historical tests missing the -30 minutes time point will be accepted. If no reserve samples are kept (only for tests performed prior to site initiation), then the details of the locally performed tests will be reviewed by the Coordinating Investigator: if the results cannot be
accepted, the patient will undergo both stimulation tests during the screening period and the samples will be analyzed by the central laboratory. At least one of the two stimulation tests (and preferably both) will be analyzed by the central laboratory. If the patient requires sex hormone priming (due to the age), and both stimulation tests must be performed during the Screening (no historical samples kept, or test was without priming), it is recommended to perform stimulation tests in consecutive setting in one day, or in two consecutive days, to avoid priming the patient twice. Local historical tests without sex-steroid priming will not be accepted for patients that require sex steroid priming according to the protocol.
3.Bone age (BA) is not older than chronological age and should be no greater than 9 years for girls and 10 years for boys.
4.Without prior exposure to any r-hGH therapy.
5.Impaired height and height velocity defined as:
a.Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age (CA) and gender according to the standards from Prader et. al, 1989 , (HT SDS = -2.0).
b.Annualized height velocity (HV) below the 25th percentile for CA (HV <-0.7 SDS) and gender according to the standards of Prader et al (1989). The interval between two height measurements should be at least 6 months, but should not exceed 18 months prior to inclusion.
6.BMI must be within ±2 SD of mean BMI for the chronological age and sex according to the 2000 CDC standards.
7.Baseline IGF-I level of at least 1 SD below the mean IGF-I level standardized for age and sex (IGF-I SDS = -1.0) according to the central laboratory reference values;
8.Children with normal fundoscopy (ophthalmoscopy) at screening (without signs/symptoms of intracranial hypertension as assessed by fundoscopy);
9.Children with multiple hormonal deficiencies must be on stable replacement therapies for other hypothalamo-pituitary-organ axes for at least 3 months and 6 months for thyroid replacement therapy prior to the first study drug administration;
10.Normal 46 XX karyotype for girls
11. Written informed consent of the parent or legal guardian of the patient and assent of the patient for the Main study and for the OLE.
Are the trial subjects under 18? yes
Number of subjects for this age range: 56
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 past or present intracranial tumor growth as confirmed by an MRI scan (with contrast).
2.History of radiation therapy or chemotherapy.
3.Malnourished children defined as:
a.Serum albumin below the lower limit of normal (LLN) according to the reference ranges of central laboratory;
b.Serum iron below the lower limit of normal (LLN) according to the reference ranges of central laboratory;
c.BMI < -2 SD for age and sex;
4.Children with psychosocial dwarfism.
5.Children born small for gestational age (SGA – birth weight and/or birth length < -2 SD for gestational age).
6.Children with idiopathic short stature.
7.Presence of anti-hGH antibodies at screening.
8.Any clinically significant abnormality likely to affect growth or the ability to evaluate growth, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, etc.
9.Patients with diabetes mellitus.
10.Patients with impaired fasting sugar (based on WHO; fasting blood sugar >110 mg/dl or 6.1 mmol/l) after repeated blood analysis.
11.Chromosomal abnormalities and medical “syndromes” (Turner’s syndrome, Laron syndrome, Noonan syndrome, Prader-Willi Syndrome, Russell-Silver Syndrome, SHOX mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia.
12.Closed epiphyses.
13.Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids and methylphenidate for attention deficit hyperactivity disorder (ADHD), with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin (DDAVP))
14.Children requiring glucocorticoid therapy (e.g. 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.
15.Major medical conditions and/or presence of contraindication to r-hGH treatment.
16.Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis.
17.Drug, substance, or alcohol abuse.
18.Known hypersensitivity to the components of study medication.
19.Other causes of short stature such as coeliac disease, hypothyroidism and rickets.
20.The patient and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct.
21.Participation in any other trial of an investigational agent within 30 days prior to Screening.



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

Health Condition(s) or Problem(s) studied

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

Pediatric Growth Hormone Deficiency

Intervention(s)

Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
INN or Proposed INN: not available
Current Sponsor code: MOD-4023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
INN or Proposed INN: not available
Current Sponsor code: MOD-4023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Genotropin
Product Name: Recombinant human Growth Hormone
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: somatropin
CAS Number: 12629-01-5
Other descriptive name: recombinant DNA-derived human growth hormone produced in E.coli
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5.3-

Primary Outcome(s)

Main Objective: To compare the safety, efficacy and tolerability of three MOD-4023
doses to that of a commercially available standard daily recombinant human growth hormone (r-hGH) formulation, in pre-pubertal children with growth failure due to insufficient secretion of endogenous growth hormone.

Primary end point(s): Annual Height Velocity in cm/year at 12 months (Baseline – Visit 1).

Secondary Objective: 1.To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of 3 different doses of MOD-4023 in pre-pubertal growth hormone deficient (GHD) children.
2.To select the optimal dose of MOD-4023 for the subsequent phase III study on the basis of safety and efficacy.

Timepoint(s) of evaluation of this end point: 12 months after the Screening

Secondary Outcome(s)

Secondary end point(s): Auxology/Clinical:
Height velocity at 6 months (Baseline – Visit 1).
Delta height SDS at 6 and 12 months (compared to Visit 1/Baseline value).
Biochemical:
Absolute IGF-I levels on day 4 after MOD-4023 dosing.
IGF-I SDS on day 4 after MOD-4023 dosing.
Other exploratory endpoints Main study and OLE):
IGFBP-3 levels on day 3 or 4 after MOD-4023 dosing.
Bone maturation every 12 months of treatment throughout (Main and OLE).
OLE endpoints:
Annual Height Velocity in cm/year at each 12 months interval.
Delta height SDS every 12 months (compared to the previous value).

Timepoint(s) of evaluation of this end point: Clinical:
6 and 12 months after the Screening
Biochemical:
day 4 after MOD-4023 dosing
Other:
-day 4 after MOD-4023 dosing
-after 12 months of treatment
OLE:
-after 12 months of treatment

Secondary ID(s)

CP-4-004

Source(s) of Monetary Support

OPKO Biologics Ltd.