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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prolor Biotech, Inc.
ClinicalTrials.gov Identifier:
NCT01225666
First received: October 19, 2010
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Adult Growth Hormone Deficiency
Drug: MOD-4023
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Dose and Frequency Finding Study of MOD-4023 in Growth Hormone Deficient Adults (GHDA)

Resource links provided by NLM:


Further study details as provided by Prolor Biotech, Inc.:

Primary Outcome Measures:
  • 1. Safety and Tolerability [ Time Frame: Following 4 weeks of MOD-4023 treatment ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Following 4 weeks MOD-4023 treatment ] [ Designated as safety issue: No ]
    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:
  • Change of IGF-I levels over time expressed in absolute and SDS values [ Time Frame: Following 4 and 16 weeks of MOD-4023 treatment ] [ Designated as safety issue: No ]
  • Change of IGFBP-3 over time expressed in absolute values [ Time Frame: Following 4 and 16 weeks of MOD-4023 treatment ] [ Designated as safety issue: No ]
  • Number of IGF-1 normalized patients in stage II [ Time Frame: Following 16 weeks of MOD-4023 treatment ] [ Designated as safety issue: No ]
    Number of patients achieving normalization of IGF-1 levels during dose titration 16-week treatment extension


Enrollment: 52
Study Start Date: August 2010
Study Completion Date: April 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Weekly low dose Drug: MOD-4023
liquid solution for subcutaneous injection - 30% of the cumulative weekly dose achieved with daily rhGH, Once weekly
Experimental: Weekly middle dose Drug: MOD-4023
liquid solution for subcutaneous injection - 45% of the cumulative weekly dose achieved with daily rhGH, Once weekly
Experimental: Weekly high dose Drug: MOD-4023
liquid solution for subcutaneous injection - 100% of the cumulative weekly dose achieved with daily rhGH, Once weekly
Experimental: Every-other week dose Drug: MOD-4023
liquid solution for subcutaneous injection - 100% of the cumulative weekly dose achieved with daily rhGH, every-other week (50% of the two-weekly cumulative dose)

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.

  Eligibility

Ages Eligible for Study:   23 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225666

Locations
Czech Republic
Internal Clinic in University Hospital St. Anna
Brno, Czech Republic, 656 91
University Hospital, 2nd Department of Internal Medicine
Hradec Kralove, Czech Republic, 500 05
Hungary
Semmelweis University, 2nd Clinic of Internal Medicine
Budapest, Hungary, 1088
State Health Center, 2nd department of internal medicine
Budapest, Hungary, 1062
Petz Aladár County Teaching Hospital, Department of Endocrinology, Metabolism and Diabetology
Gyor, Hungary, 9023
University of Pécs, Medical School, 1st Department of Internal Medicine
Pécs, Hungary, 7624
Szeged University, 1st Internal Medicine Clinic, Endocrinology
Szeged, Hungary, 6720
Hetényi Géza Hospital and Out-Patient Clinic, 1st Department of Internal Medicine
Szolnok, Hungary, 5004
Israel
Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center
Jerusalem, Israel, 91120
Institute of Endocrinology, Tel Aviv-Sourasky Medical Center
Tel Aviv, Israel, 64239
Serbia
Clinical Center of Serbia, Institute for endocrinology, diabetes and metabolism disease
Belgrade, Serbia, 11000
Slovakia
. Department of Internal Medicine V, University Hospital Ruzinov
Bratislava, Slovakia, 82104
Slovak Health University, Division of Endocrinology
Bratislava, Slovakia, 83307
National Institute of Endocrinology and Diabetology
Lubochna, Slovakia, 034 91
Slovenia
University Medical Centre Ljubljana, Department of Endocrinology, Diabetes and Metabolic Diseases
Ljubljana, Slovenia, 1525
Sponsors and Collaborators
Prolor Biotech, Inc.
  More Information

No publications provided

Responsible Party: Prolor Biotech, Inc.
ClinicalTrials.gov Identifier: NCT01225666     History of Changes
Other Study ID Numbers: CP-4-003, 2010-019374-32
Study First Received: October 19, 2010
Last Updated: December 23, 2013
Health Authority: United States: Food and Drug Administration
Hungary: National Institute of Pharmacy
Czech Republic: State Institute for Drug Control
Slovakia: State Institute for Drug Control
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovenia: Agency for Medicinal Products - Ministry of Health
Israel: Ministry of Health

Keywords provided by Prolor Biotech, Inc.:
MOD-4023
Growth Hormone Deficient Adults
Phase II

Additional relevant MeSH terms:
Dwarfism, Pituitary
Bone Diseases
Bone Diseases, Developmental
Bone Diseases, Endocrine
Brain Diseases
Central Nervous System Diseases
Dwarfism
Endocrine System Diseases
Hypopituitarism
Hypothalamic Diseases
Musculoskeletal Diseases
Nervous System Diseases
Pituitary Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014