A Phase II, Dose and Frequency Finding Study of MOD-4023 in Growth Hormone Deficient Adults (GHDA)

• Register: EUCTR
• Last refreshed on: 7 August 2012
• Main ID: EUCTR2010-019374-32-SK
• Date of registration: 14/05/2010
• Prospective Registration: Yes
• Primary sponsor: ModigeneTech Ltd.
• Public title: A Phase II, Dose and Frequency Finding Study of MOD-4023 in Growth Hormone Deficient Adults (GHDA)
• Scientific title: A Phase II, Dose and Frequency Finding Study of MOD-4023 in Growth Hormone Deficient Adults (GHDA)
• Date of first enrolment: 15/07/2010
• Target sample size: 56
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019374-32
• 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

Countries of recruitment

Czech Republic, Germany, Hungary, Slovakia, Slovenia

Key inclusion & exclusion criteria

Inclusion criteria:
Genders Eligible for Study: Both
Ages Eligible for Study: Males - 23 to 60 years, Females – 23 to 50
years.
1. GHDA subjects as defined in the Consensus guidelines for the
diagnosis and treatment of adults with GH deficiency II
(2007).
2. Patients using hormonal replacement therapy(s) for
deficiencies of other hypothalamo-pituitary axes must be on an
optimized and stable treatment regimen (hormone levels within
normal ranges on screening) for at least three months prior to
screening:
a. Temporary adjustment of glucocorticoid replacement
therapy, as appropriate, is acceptable.
b. Peripheral thyroid hormones (FT4, FT3) within the
normal range.
3. Fertile females must agree to use appropriate contraceptive
methods
4. Female patients must have a negative serum pregnancy test at
inclusion.
5. GH replacement therapy for more than 6 months with
registered GH product.
6. The IGF-I level at screening within -2 to +2 SDS of the age
and sex normal ranges according to the central laboratory
measurements.1
7. Body Mass Index (BMI, kg/m2) of 19.0 to 35.0 kg/m2, both
inclusive
8. Confirmed to be negative for anti r-hGH antibodies at the time
of screening.
9. Willing and able to provide written informed consent prior to
performing any study procedures.
Are the trial subjects under 18? no
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:
Females who are pregnant or breast-feeding
2. Evidence of growth of pituitary adenoma or other intracranial
tumor within the last 12 months (confirmed by computer
tomography (CT) or magnetic resonance imaging (MRI) scan
(with contrast) within 3 months prior to study entry or at
screening).
3. History of malignancy other than i) cranial irradiation (for
cranial tumor or leukemia) causing GHD or ii) fully treated
basal cell carcinoma
4. Signs of intracranial hypertension at screening
5. Heart insufficiency, NYHA class greater than 2
6. History of impaired glucose tolerance, insulin resistance or
overt diabetes mellitus defined according to the American
Diabetes Association (ADA) Criteria
7. Impaired liver function defined as elevation of liver enzymes >2
x upper limit of normal
8. Impaired kidney function defined as increased serum creatinine
levels >1.5 x upper limit of normal
9. Active acromegaly in the last 18 months and less than 6 months
of active r-hGH replacement therapy
10. Active Carpal tunnel syndrome
11. Prader-Willi syndrome
12. Active Cushing's syndrome within the last 12 months
13. Systemic corticosteroids other than in replacement doses within
the 3 months before study entry (temporary adjustment of
glucocorticoids, as appropriate, is acceptable)
14. Anabolic steroids other than gonadal steroid replacement
therapy within 2 months before study entry
15. History of non-compliance with medications, uncooperativeness
or drug abuse
16. Blood donation or any major blood loss >500 mL within the
past 90 days prior to study entry
17. Patients who, based on the investigator’s judgment, have a
clinically significant or unstable medical or surgical condition
that may preclude safe and complete study participation.
Conditions may include cardiovascular, peripheral vascular,
pulmonary, hepatic, renal, or neurological disease, as
determined by medical history, physical examination,
laboratory tests or ECG
18. Patients who participated in any investigational medicinal
product (IMP) study within the last 2 months
19. History of positive serology to HBC, HBV and HIV


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

Health Condition(s) or Problem(s) studied

Growth Hormone Deficiency
MedDRA version: 12.1 Level: LLT Classification code 10056438 Term: Growth hormone deficiency

Intervention(s)

Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
Current Sponsor code: MOD-4023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Genotropin
Product Name: recombinant human Growth Hormone (rhGH)
Pharmaceutical Form: Powder 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 milligram(s)
Concentration type: range
Concentration number: 5,3-13.8

Trade Name: Humatrope
Product Name: recombinant human Growth Hormone(rhGH)
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: somatropin
CAS Number: 12629-01-5
Other descriptive name: recombinanat DNA-derived human growth hormone produced in E.coli
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 1.9-7.6

Trade Name: Norditropin Simplex
Product Name: recombinant human Growth Hormone(rhGH)
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: somatropin
CAS Number: 12629-01-5
Other descriptive name: recombinanat DNA-derived human growth hormone produced in E.coli
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 3,33-10

Trade Name: Saizen
Product Name: recombinant human Growth Hormone(rhGH)
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: somatropin
CAS Number: 12629-01-5
Other descriptive name: recombinanat DNA-derived human growth hormone produced in E.coli
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5,83-

Trade Name: NutropinAq
Product Name: recombinant human Growth Hormone(rhGH)
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: somatropin
CAS Number: 12629-01-5
Other descriptive name: recombinanat DNA-derived human growth

Primary Outcome(s)

Main Objective: To assess the safety, tolerability and Pharmacokinetics/
Pharmacodynamics (PK/PD) profile of three doses of MOD-4023 on a
weekly regime and one dose on an EOW regime administered for a
period of 4 weeks in Growth Hormone Deficient Adult (GHDA)
patients who previously were on a stable r-hGH treatment.

Primary end point(s): The primary efficacy endpoint will be the mean time interval of IGF-I
levels that lay within ±1.5 SDS after the last dose administration during
stage I expressed in hours.
Secondary efficacy endpoints:
1. Change of IGF-I levels over time in stage I and stage II expressed in
absolute and SDS values
2. Change of IGF-PB3 over time in stage I and stage II expressed in
absolute and SDS values
3. Time to achieve normalization of IGF-I during dose titration in
stage II

Safety assessments will consist of monitoring and recording:
1. Adverse events throughout the study
2. Immunogenicity of MOD 4023 (development of neutralizing
antibodies)
3. Changes in vital signs and physical examination
4. Change in body weight
5. Fundoscopy for the occurrence of increased intracranial
pressure
6. Change in the parameters of glucose metabolism:
a. Fasting insulin level
b. Fasting glucose levels
c. HbA1c levels
7. Status of other hormonal axes:
a. Thyroid hormones (free T4 and TSH)
b. Cortisol levels
8. Laboratory parameters, including serum chemistry profile,
liver enzymes, hematology, lipoproteins and urinalysis
9. Local tolerability (Injection site reaction)
10. Relationship of IGF-I and IGFBP3 changes

PK/PD endpoints:Blood samples for analysis of serum concentrations will be collected
prior to dosing with the investigational product and at additional time
points after dosing. All serum samples from subjects who received
MOD-4023 will be analyzed for parent drug using a validated bio
analytical method. Pharmacokinetic parameters will be calculated
using standard methods. Analyses of dose proportionality and other
pertinent comparisons of pharmacokinetic parameters across or
between dosage levels will be performed, using appropriate statistical
methods.
The pharmacodynamics of MOD-4023 will be assessed by examining
blood levels of insulin-like growth factor-1 (IGF-I) and insulin-like
growth factor binding protein 3 (IGFBP-3). Analyses of dose
proportionality and other pertinent comparisons of pharmacodynamics
parameters across or between dosage levels will be performed, using
appropriate statistical methods. In Period II, exploratory analyses of
the clinical endpoints will also be performed.
A population PK and PK/PD modeling will be performed. The final
PK model will be used to predict PK concentrations for the PK/PD
modeling and to simulate and explore various dosing regimen
scenarios to support the design of future clinical studies with MOD-
4023.

Secondary Objective: 1. To select the optimal dose and dosing regimen of MOD-4023
for the subsequent phase III study on the basis of safety and
PK/PD profile after 4 and 12 weeks of treatment.
2. To assess the long term safety and tolerability of MOD-4023
after 12 weeks dose administration.
3. To develop a population PK and PK/PD relationship model
that may be utilized in later studies to predict PK
concentrations for the PK/PD modeling and to simulate and
explore various dosing regimen scenarios for further
Modigenetech studies.

Secondary ID(s)

CP-4-003