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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2013-000830-37-AT
• Date of registration: 11/07/2013
• Prospective Registration: Yes
• Primary sponsor: OPKO Biologics Ltd.
• Public title: Treatment with Long Acting hGH Product in Adult subjects with Growth Hormone Deficiency
• Scientific title: A Phase 3, Multicenter Study Designed to Evaluate the Efficacy and Safety of a Long Acting hGH Product (MOD-4023) in Adult Subjects with Growth Hormone Deficiency
• Date of first enrolment: 29/08/2013
• Target sample size: 190
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000830-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, France, Georgia, Germany, Greece, Hungary, Israel, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Regulatory Operations Europe
• Affiliation: inVentiv Health Clinical UK Ltd.

• Name: Regulatory Operations Europe
• Affiliation: inVentiv Health Clinical UK Ltd.

Key inclusion & exclusion criteria

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 rhGH replacement therapy or use of GH secretagogues for at least 9 months with any registered or investigational rhGH 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 males 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 post-menopausal 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 with adequate compliance
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 recurrence-free 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, well-controlled 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 5(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 (investigational or approved) that impa

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

Health Condition(s) or Problem(s) studied

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

Adult or childhood onset growth hormone deficiency (GHD)
MedDRA version: 20.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
INN or Proposed INN: na
CAS Number: na
Current Sponsor code: MOD-4023
Other descriptive name: RECOMBINANT HUMAN GROWTH HORMONE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
INN or Proposed INN: na
CAS Number: na
Current Sponsor code: MOD-4023
Other descriptive name: RECOMBINANT HUMAN GROWTH HORMONE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
INN or Proposed INN: na
CAS Number: na
Current Sponsor code: MOD-4023
Other descriptive name: RECOMBINANT HUMAN GROWTH HORMONE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Change in trunk fat mass (FM), expressed in kilograms measured with DXA, from baseline to 26 weeks.

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)
•To evaluate the safety and tolerability of MOD-4023 over placebo in adult subjects with GHD
•To determine the IGF-I and IGFBP-3 serum levels
• To monitor long-term safety and efficacy of MOD-4023 in adult subjects
with GHD who completed Treatment Periods I and II of this study

Timepoint(s) of evaluation of this end point: Baseline and Week 26

Secondary Outcome(s)

Secondary end point(s): Changes in body composition:
•Change in total FM, expressed in kilograms, measured with DXA, from baseline to 26 and 52 weeks
•Change in lean body mass, expressed in kilograms measured with DXA, from baseline to 26 and 52 weeks
•Change in trunk FM, expressed in kilograms measured with DXA, from baseline to 52 weeks
•Change in trunk FM, expressed as % change from baseline, measured with DXA, from baseline to 26 and 52 weeks
Change in Biochemical markers:
•Change of IGF-I and IGF-I SDS levels across study visits
•Change of IGFBP-3 levels across study visits
•Proportion of subjects achieving normalization of IGF-I levels during
and at the end of each treatment period (week 26, week 52 and end-of-study).
Additional Measurements:
•Change in QoL from baseline across study visits
•Change in Waist-to-hip ratio from baseline across study visits
•Change in bone density from baseline on a yearly basis during Treatment Period III
•Change in fat and lean body mass from baseline on a yearly basis during Treatment Period III
•Change in lipid profile: fasting HDL cholesterol, LDL cholesterol,
triglycerides, Lp(a) from baseline on a six-monthly basis.

Safety and Tolerability
•AEs and local tolerability (injection site reaction)
•Parameters of glucose metabolism:
-Fasting insulin level
-Fasting glucose levels
-HbA1c levels
•Immunogenicity
-Anti MOD-4023 Neutralizing Antibody occurrence
•IGF-I levels
•MOD-4023 levels
•Status of other hormonal axes
-Thyroid hormones (Free T4, T3 and TSH)
-Morning cortisol levels
-Prolactin levels (screening, 6 months, 12 months)
•Other safety laboratory parameters, including serum chemistry profile, liver enzymes, hematology and urinalysis
•Vital signs including body mass index (BMI)
•ECG (screening, 6 months, 12 months and yearly thereafter)
•Fundoscopy for the occurrence of increased intracranial pressure (if PI feels it is required)

Timepoint(s) of evaluation of this end point: Changes in body composition from baseline to 26 and 52 weeks

Change in Biochemical markers across the visits

Additional Measurements

Safety and Tolerability

Secondary ID(s)

2013-000830-37-HU

CP-4-005

Source(s) of Monetary Support

OPKO Biologics Ltd.

Ethics review

Status: Approved
Approval date:
Contact: