Treatment with Long Acting hGH Product in Adult subjects with Growth Hormone Deficiency

Phase 1

• Conditions: Adult or childhood onset growth hormone deficiency (GHD); MedDRA version: 20.0Level: PTClassification code 10056438Term: Growth hormone deficiencySystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2013-000830-37-SK
• Lead Sponsor: OPKO Biologics Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-24
• Last Update Posted: 4 December 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

1. Men and women between the age of 23 to 70 years old at screening,
inclusive
2. GHD subjects as defined in the Consensus guidelines for the diagnosis
and treatment of adults with GH deficiency II (2007). The following
cutoff values for the diagnosis of GHD will be used
• Insulin tolerance test or glucagon test, the validated cutoff for GHD in
adults is a peak GH response = 3 µg/L
• Growth-hormone-releasing hormone (GHRH) + arginine : for those
with a body mass index:
- BMI <25 kg/m2, a peak GH =11 µg/L;
- BMI 25–30 kg/m2 (included), a peak GH=8 µg/L;
- BMI >30 kg/m2, a peak GH=4 µg/L.
3. Subjects 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:
• Temporary adjustment of glucocorticoid replacement therapy, as
appropriate, is acceptable.
• Peripheral thyroid hormones (FT4) within the normal range of the
central or local lab .
• Adrenal insufficiency – documented adrenal status (subjects that are
sufficient with documented test in last 6 months or insufficient and on
stable replacement.
4. Subjects with Diabetes Insipidus should be on stable treatment for at
least 6 months
5. No r-hGH replacement therapy or use of GH secretagogues for at least
9 months with any registered or investigational r-hGH or GH
secretagogue product.
6. The IGF-I level at screening =-1 SDS of the age and sex normal
ranges according to the central laboratory measurements.
7. For patients treated for Cushing's, at least two years elapsed since
pituitary surgery and in biochemical remission without current medical
therapy for the condition, documented within 6 months of study entry
8. Body Mass Index (BMI, kg/m2) of 23.0 to 35.0 kg/m2, both inclusive
9. Confirmed to be negative for anti r-hGH antibodies at the time of
screening.
10. Women of childbearing potential and fertile men must agree to use
appropriate contraceptive methods during the study until one month
after the last study visit. For the purposes of this protocol, a history of
tubal ligation, bilateral oophorectomy or hysterectomy, or postmenopausal
women constitutes non-fertility. Fertile men must agree to
use a barrier contraceptive (condom). Vasectomy older than 6 months is
also acceptable.
11. Women of childbearing potential must have a negative serum
pregnancy test at inclusion.
12. Subjects who are on a stable diet and exercise regime and do not
have plans to modify their diet or exercise for at least 12 months.
13. Subject had a DXA screening and the results are interpretable
according to the study plan.
14. Willing and able to provide written informed consent prior to
performing any study procedures.
Inclusion into Treatment Period III (LT-OLE):
1. Completion of Treatment Periods I and II of study CP-4-005
2. Signing consent form for Treatment Period III
3. Investigator's approval of the patient anticipated compliance and
safety
4.Agreement to continue with use of contraception in women of child
bearing potential and fertile men

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 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Women who are pregnant or breast-feeding (at least 6 months delay
from childbirth or lactation)
2. Evidence of growth benign intracranial tumor within the last 12
months (determined by comparing a previous MRI to a new one
obtained no more than 6 months prior to study entry to clarify dynamics of growth).
3. Suspected or diagnosed ongoing cancer or history of any cancer.
Exceptions to this exclusion criterion include resected in situ carcinoma
of the cervix and squamous cell or basal cell carcinoma of the skin with
complete local excision. Patients with GHD attributed to treatment of
intracranial malignant lesions in childhood or adulthood (or, tumors) or
leukemia may also be enrolled into the study provided that a recurrencefree
survival period of at least 5 years is well documented in the study record.
4. Signs of intracranial hypertension at screening
5. Heart insufficiency, NYHA class > 2 (Appendix C)
6. History of overt diabetes mellitus (including currently treated, wellcontrolled
DM) defined according to the American Diabetes Association
(ADA) Criteria , including ongoing administration of anti-diabetic
medications/agents. A history of gestational diabetes, resolved after childbirth, is not exclusionary.
7. Impaired liver function defined as:
a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
greater than three times the upper limit of normal (ULN) at Screening
visit in a patient without prior history of elevated LFTs (non-alcoholic
fatty liver disease is not excluded, but requires etiological clarification
prior to eligibility confirmation) OR
b. Total bilirubin greater than 2 times the ULN at Screening
8. Subjects with severe renal failure at the Screening visit (defined by
GFR < 30 mL/min using MDRD Study Equation)
9. History of Acromegaly
10. For patients treated for Cushing's, biochemical, documented
evidence of possible recurrence within 2 months of study entry
according to 2008 Endocrine Society Guideline
11. Active Carpal tunnel syndrome suspected on a recent history (last 6
months) or ongoing symptoms such as: Numbness, or tingling in hand
and/or finger, pain in the arm, palm or forearm, both occurring also at
night and with intensive use of the hand; trouble gripping objects and
weakness in the thumb.
12. Systemic corticosteroids other than in replacement doses within the
3 months before study entry (temporary adjustment of glucocorticoids,
as appropriate, is acceptable)
13. Anabolic therapy or supplements (subject to Medical Monitor's
decision) other than gonadal steroid replacement therapy within 2
months before study entry
14. History of non-compliance with medications, un-cooperativeness or
drug abuse
15. Subjects 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.
16. Subjects who participated in any study and had administration of an
investigational medicinal product (IMP) within the last 2 months.
Subjects with previous participation in investigational studies must have
recovered from all adverse effects.
17. Subjects who participated within the last 12 months in any clinical
trial involving the use of medicinal products (investi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate a clinical superiority of MOD-4023 over placebo in terms of decrease in Fat Mass (FM) in adult subjects with GHD ;Secondary Objective: •To determine the efficacy of MOD-4023 over placebo in other body composition variables (such as lean body mass and waist-to-hip ratio)<br>•To evaluate the safety and tolerability of MOD-4023 over placebo in adult subjects with GHD<br>•To determine the IGF-I and IGFBP-3 serum levels<br>• To monitor long-term safety and efficacy of MOD-4023 in adult<br>subjects with GHD who completed Treatment Periods I and II of this<br>study;Primary end point(s): Change in trunk fat mass (FM), expressed in kilograms measured with<br>DXA, from baseline to 26 weeks;Timepoint(s) of evaluation of this end point: Baseline and Week 26