A Phase IIb study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of ARX201 Following Repeated Dosing to Young Adult Patients with Childhood Onset Growth Hormone Deficiency (GHD)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-001746-40-HU
• Date of registration: 02/04/2007
• Prospective Registration: Yes
• Primary sponsor: Ambrx, Inc., USA
• Public title: A Phase IIb study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of ARX201 Following Repeated Dosing to Young Adult Patients with Childhood Onset Growth Hormone Deficiency (GHD)
• Scientific title: A Phase IIb study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of ARX201 Following Repeated Dosing to Young Adult Patients with Childhood Onset Growth Hormone Deficiency (GHD)
• Date of first enrolment: 25/08/2008
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001746-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
1. Young adults, male or female, age 18 to 30 years, with growth
hormone deficiency of childhood onset whom have completed growth
(and in the investigators opinion have achieved their final height);
2. hGH level below the predetermined cut-off value in one of the dynamic
endocrine testing (If there are more than two tests performed all should
have peak hGH levels below predetermined cut-off values):
a. If Insulin Tolerance Test, the peak hGH value must be below 3
ng/ml;
b. If Arginine-GHRH Test, the peak hGH value must be below 5
ng/ml. This test is however not acceptable in patients with
GHD of hypothalamic origin (e.g. patients having received
irradiation of the hypothalamic-pituitary region);
c. If Arginine Test alone, the GH peak must be below 1.4 ng/ml.
This test is acceptable only in patients in which Insulin
Tolerance Test is contraindicated and are suffering from GHD
of hypothalamic origin;
OR
d. Patients without results of any dynamic endocrine testing
having at least 3 other pituitary hormone deficiencies;
3. Screening IGF-I level of = - 2 SDS standardised for age and sex
according to the central laboratory reference values;
4. rhGH treatment naïve or stopped this treatment for at least 6 months
prior to study entry ;
5. Receiving replacement therapies for any other hypothalamic-pituitary
axes deficiencies for at least 3 months prior to study entry; (For
patients receiving estrogen, ONLY transdermal application is
acceptable. Temporary adjustment of glucocorticoid replacement
therapy, as appropriate, is acceptable)
6. Confirmed to be negative for anti-hGH antibodies;
7. Females must not intend to conceive during or shortly after the study.
They must be either post-menopausal, surgically incapable of bearing
children, or practicing an acceptable method of birth control (e.g.,
intrauterine device or spermicide and barrier but NOT hormonal
contraceptives) and be willing to continue the same method of birth
control during and for 30 days after the last dose of study medication.
Oral contraceptives must be discontinued at least 14 days prior to
receipt of the first dose of study drug and are not permitted during the
study. Females of child-bearing potential must have a negative serum
pregnancy test at screening and a negative urine pregnancy test before
the first dose of study drug;
8. Have negative drugs of abuse screen at Screening and on Day -1 of
check in ;
9. Willing and able to give informed consent; and
10. Willing and able to undergo procedures required by this protocol.
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:
1. Evidence of growth of pituitary adenoma or other intracranial tumor
within the last 12 months which has to be confirmed by computer
tomography (CT) or magnetic resonance imaging (MRI) scan (with
contrast) within 3 months prior to study entry. Patients with primary
growth hormone deficiency are exempt from this requirement
2. History of malignancy other than I) cranial tumor or leukemia causing
GHD or II) fully treated basal cell carcinoma;
3. Subjects presenting with any clinically significant ECG abnormality,
including a corrected QT interval (QTc) > 450 msec for males or a
corrected QT interval (QTc) > 470 msec for females using Bazett’s
formula ;
4. Evidence of active malignancy or concurrent anti-tumor therapy;
5. Evidence of intracranial hypertension;
6. Significant hepatic dysfunction (persistent elevation of alanine
transaminase [ALT] or aspartate transaminase [AST] >1.5 x upper limit
of normal);
7. Significant renal impairment as indicated by serum creatinine levels
above the normalized range for age;
8. Any other major medical conditions, including e.g., clinically manifest
diabetes mellitus, hypertension, tuberculosis, major surgery within the
last three months, or significantly abnormal laboratory tests (e.g.,
disturbed calcium homeostasis); or any other conditions (e.g., acute
infections) that may influence drug absorption, metabolism or excretion
or that may interfere with any study variables in the judgment of the
investigator;
9. Inadequate T4 or adrenocorticoid replacement;
10. Positive results from serology examination for HBV, HCV or HIV;
11. History of alcohol or drug abuse as specified by the Diagnostic and
Statistical Manual of Mental Disorders, 4th edition (DSM-IV) in the year
before screening;
12. Hypersensitivity to the study treatment;
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, un-cooperativeness or
drug abuse;
16. Blood donation or any major blood loss >500 mL within the past 90
days prior to study entry;
17. History of any medical or psychiatric condition that in the opinion of the
investigator would pose a risk for participation in this study or interfere
with the compliance needed for this study;
18. Females who are pregnant or breast-feeding;
19. History of poor compliance with other chronic therapy; and
20. Participation in any other trial of an investigational agent within 90 days
prior to screening.


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

Health Condition(s) or Problem(s) studied

Growth Hormone Deficiency
MedDRA version: 9.1 Level: LLT Classification code 10056438 Term: Growth hormone deficiency

Intervention(s)

Product Code: ARX201
Pharmaceutical Form: Powder for injection*
Current Sponsor code: PEG-ahGH
Other descriptive name: Pegylated recombinant human growth hormone
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 13.2-

Primary Outcome(s)

Primary end point(s): • Primary efficacy endpoint
- Temporal profiling of circulating IGF-I levels
• Secondary efficacy endpoints
- Biochemical endpoints (IGF-1, and IGFBP-3 will also serve as pharmacodynamic endpoints):
a) IGF-1 SDS; changes to baseline in IGF-I level, IGF-I SDS;
b) IGFBP-3, IGFBP-3 SDS (actual values and changes to baseline)
c) Lipid parameters (Cholesterol, LDL, HDL, triglycerides; actual values and changes to baseline)
• Clinical endpoints:
a) Change in body fat mass (FM) expressed in kg-s from the baseline to the end of study as measured with DXA
b) Relative change in body fat,
c) Change in trunk fat (kg-s)
d) Relative change in trunk fat
e) Change in lean body mass (LBM) expressed in kg-s; from the baseline to the end of study (as measured with DXA)
f) Change in waist circumference
g) Change in hip circumference
h) Change in waist-to-hip ratio
i) Change in sum of skinfolds thickness
j) Change in BMI
k) Change in QoL scores

Secondary Objective: - To establish the single and multidose pharmacokinetic and pharmacodynamic profiles of ARX201 administered to young adult patients with childhood onset GHD.
- To select, based on the safety, pharmacokinetic, and pharmacodynamic findings, the dosage regimens of ARX201 that will be evaluated in subsequent multiple dose studies in patients with GHD.
- To evaluate the efficacy of ARX201 following six months of treatment in young patients with GHD.

Main Objective: The primary objective is to evaluate the safety, tolerability, and pharmacodynamic response of three different ARX201 doses when administered repeatedly to young adult patients with childhood onset GHD

Secondary ID(s)

PRO-ARX201-701