MOD-4023 (Long-Lasting Human Growth Hormone (hGH)) Study in Growth Hormone Deficient Adults (GHDA)

Phase 2

Completed

Conditions: Adult Growth Hormone Deficiency

Interventions: Drug: MOD-4023

Registration Number: NCT01225666

Lead Sponsor: OPKO Health, Inc.

Brief Summary: This study aims 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 every-other-week regime administered for a period of 4 weeks in Growth Hormone Deficient Adult (GHDA) patients who previously were on a stable r-hGH treatment. An additional extension period of 16 weeks once-weekly administration of MOD-4023 aims to confirm the dose selection for future trials.

Detailed Description: The study is a phase II, randomized, open-label, parallel, 4 active treatment arms study to evaluate the safety, tolerability and PK/PD profile of MOD-4023 in pre-treated, normalized, GHD adults.

The study is conducted in 2 stages. Stage I is a 4-week treatment period with 4 different dose levels/dosing regimens.

Stage II is a 16-week treatment-extension period in which all the patients will start with the same dose (derived from stage I) and will be dose titrated to maintain IGF-1 levels within the normal range.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 52

Inclusion Criteria

Genders Eligible for Study: Both
Ages Eligible for Study: Males - 23 to 60 years, Females - 23 to 50 years.
GHDA subjects as defined in the Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II (2007).
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:
- Temporary adjustment of glucocorticoid replacement therapy, as appropriate, is acceptable.
- Peripheral thyroid hormones (FT4, FT3) within the normal range.
Fertile females must agree to use appropriate contraceptive methods
Female patients must have a negative serum pregnancy test at inclusion.
Growth Hormone (GH) replacement therapy for more than 6 months with registered GH product.
The IGF-I level at screening within -1.5 to +1.5 SDS of the age and sex normal ranges according to the central laboratory measurements.
Body Mass Index (BMI, kg/m2) of 22.0 to 35.0 kg/m2, both inclusive
Confirmed to be negative for anti r-hGH antibodies at the time of screening.
Willing and able to provide written informed consent prior to performing any study procedures.

Exclusion Criteria

Females who are pregnant or breast-feeding
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).
History of malignancy other than i) cranial irradiation (for cranial tumor or leukemia) causing GHD or ii) fully treated basal cell carcinoma
Signs of intracranial hypertension at screening
Heart insufficiency, NYHA class greater than 2
History of impaired glucose tolerance, insulin resistance or overt diabetes mellitus defined according to the American Diabetes Association (ADA) Criteria
Impaired liver function defined as elevation of liver enzymes >2 x upper limit of normal
Impaired kidney function defined as increased serum creatinine levels >1.5 x upper limit of normal
Active acromegaly in the last 18 months and less than 6 months of active r- hGH replacement therapy
Active Carpal tunnel syndrome
Prader-Willi syndrome
Active Cushing's syndrome within the last 12 months
Systemic corticosteroids other than in replacement doses within the 3 months before study entry (temporary adjustment of glucocorticoids, as appropriate, is acceptable)
Anabolic steroids other than gonadal steroid replacement therapy within 2 months before study entry
History of non-compliance with medications, un-cooperativeness or drug abuse
Blood donation or any major blood loss >500 mL within the past 90 days prior to study entry
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
Patients who participated in any investigational medicinal product (IMP) study within the last 2 months
History of positive serology to HBC, HBV and HIV

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Weekly low dose	MOD-4023	MOD-4023
Every-other week dose	MOD-4023	MOD-4023
Weekly middle dose	MOD-4023	MOD-4023
Weekly high dose	MOD-4023	MOD-4023

Primary Outcome Measures

Name	Time	Method
1. Safety and Tolerability	Following 4 weeks of MOD-4023 treatment	Adverse events (AE's), vital signs, electrocardiogram (ECG), laboratory tests, local reaction
Maintenance of normal Insulin-like-Growth-Factor-1 (IGF-1)levels in GHDA	Following 4 weeks MOD-4023 treatment	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 (4w treatment) expressed in hours.

Secondary Outcome Measures

Name	Time	Method
Change of IGF-I levels over time expressed in absolute and SDS values	Following 4 and 16 weeks of MOD-4023 treatment
Number of IGF-1 normalized patients in stage II	Following 16 weeks of MOD-4023 treatment	Number of patients achieving normalization of IGF-1 levels during dose titration 16-week treatment extension
Change of IGFBP-3 over time expressed in absolute values	Following 4 and 16 weeks of MOD-4023 treatment

Trial Locations

Locations (15): Hetényi Géza Hospital and Out-Patient Clinic, 1st Department of Internal Medicine
🇭🇺
Szolnok, Hungary
Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center
🇮🇱
Jerusalem, Israel
Semmelweis University, 2nd Clinic of Internal Medicine
🇭🇺
Budapest, Hungary
University of Pécs, Medical School, 1st Department of Internal Medicine
🇭🇺
Pécs, Hungary
Slovak Health University, Division of Endocrinology
🇸🇰
Bratislava, Slovakia
National Institute of Endocrinology and Diabetology
🇸🇰
Lubochna, Slovakia
University Medical Centre Ljubljana, Department of Endocrinology, Diabetes and Metabolic Diseases
🇸🇮
Ljubljana, Slovenia
State Health Center, 2nd department of internal medicine
🇭🇺
Budapest, Hungary
Internal Clinic in University Hospital St. Anna
🇨🇿
Brno, Czechia
University Hospital, 2nd Department of Internal Medicine
🇨🇿
Hradec Kralove, Czechia
Petz Aladár County Teaching Hospital, Department of Endocrinology, Metabolism and Diabetology
🇭🇺
Gyor, Hungary
Szeged University, 1st Internal Medicine Clinic, Endocrinology
🇭🇺
Szeged, Hungary
Institute of Endocrinology, Tel Aviv-Sourasky Medical Center
🇮🇱
Tel Aviv, Israel
Clinical Center of Serbia, Institute for endocrinology, diabetes and metabolism disease
🇷🇸
Belgrade, Serbia
. Department of Internal Medicine V, University Hospital Ruzinov
🇸🇰
Bratislava, Slovakia