Safety and Efficacy Phase 2 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children

Study Overview

Brief Summary

This is a phase II, open label, active-controlled, randomized safety and dose finding study of different MOD-4023 dose levels compared to daily r-hGH therapy in pre-pubertal growth hormone deficient children.

Official Title

Safety and Dose Finding Study of Different MOD-4023 Dose Levels Compared to Daily r-hGH Therapy in Pre-pubertal Growth Hormone Deficient Children

Conditions 

Pediatric Growth Hormone Deficiency

Intervention / Treatment 

• Drug: MOD-4023
• Drug: Somatropin

Other Study ID Numbers 

• CP-4-004
• 2011-004553-60 ( EudraCT Number )

Study Start 

2012-02

Primary Completion (Actual) 

2015-07

Study Completion (Actual) 

2015-07

Enrollment (Actual) 

56

Study Type Interventional

Phase Phase 2

Resource links provided by the National Library of Medicine 

MedlinePlus Genetics

 related topics:  Isolated growth hormone deficiencyDrug Information

 available for:  SomatrogonFDA Drug and Device Resources

Contacts and Locations

This section provides contact details for people who can answer questions about joining this study, and information on where this study is taking place.

To learn more, please see the Contacts and Locations section in How to Read a Study Record.

This study has 4 locations

Greece

Athens, Greece

Children’s Hospital “P. A. Kyriakou”

Hungary

Budapest, Hungary

Buda Children’s Hospital

Budapest, Hungary

Heim Pal Children’s Hospital

Slovakia

Košice, Slovakia

Children’s University Hospital

Click to view interactive map

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

Description

Inclusion Criteria:

1. Pre-pubertal child aged ≥ 3 yrs old and not above 10 years for girls or 11 years for boys with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone deficiency.
2. Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak plasma GH level of ≤7 ng/ml, determined by central laboratory using a validated assay .
3. Bone age (BA) is not older than chronological age and should be no greater than 9 years for girls and 10 years for boys.
4. Without prior exposure to any r-hGH therapy.
5. Normal birth size, birth weight and length for gestational age
6. Impaired height and height velocity defined as:
   1. Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age (CA) and gender according to the standards from Prader et. al, 1989 , (HT SDS ≤ -2.0).
   2. Annualized height velocity (HV) below the 25th percentile for CA (HV <-0.7 SDS) and gender according to the standards of Prader et al (1989). The interval between two height measurements should be at least 6 months before inclusion.
7. BMI must be within ±2 SD of mean BMI for the chronological age and sex according to the 2000 CDC standards.
8. Baseline IGF-I level of at least 1 SD below the mean IGF-I level standardized for age and sex (IGF-I SDS ≤ -1.0) according to the central laboratory reference values;
9. 12. Written informed consent of the parent or legal guardian of the patient and assent of the patient (if the patient can read).

Exclusion Criteria:

1. Children with past or present intracranial tumor growth as confirmed by an MRI scan (with contrast).
2. History of radiation therapy or chemotherapy.
3. Malnourished children defined as:
   1. Serum albumin below the lower limit of normal (LLN) according to the reference ranges of central laboratory;
   2. Serum iron below the lower limit of normal (LLN) according to the reference ranges of central laboratory;
   3. BMI < -2 SD for age and sex;
4. Children with psychosocial dwarfism.
5. Children born small for gestational age (SGA – birth weight and/or birth length < -2 SD for gestational age).
6. Presence of anti-hGH antibodies at screening.
7. Any clinically significant abnormality likely to affect growth or the ability to evaluate growth, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, etc.
8. Patients with diabetes mellitus.
9. Patients with impaired fasting sugar (based on WHO; fasting blood sugar >110 mg/dl or 6.1 mmol/l) after repeated blood analysis.
10. Chromosomal abnormalities and medical “syndromes” (Turner’s syndrome, Laron syndrome, Noonan syndrome, Prader-Willi Syndrome, Russell-Silver Syndrome, SHOX mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia.
11. Closed epiphyses.
12. Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids and methylphenidate for attention deficit hyperactivity disorder (ADHD), with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin (DDAVP))
13. Children requiring glucocorticoid therapy (e.g. asthma) who are taking a dose of greater than 400 µg/d of inhaled budesonide or equivalents for longer than 1 month during a calendar year.
14. Major medical conditions and/or presence of contraindication to r-hGH treatment.
15. Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis.
16. Drug, substance, or alcohol abuse.
17. Known hypersensitivity to the components of study medication.
18. Other causes of short stature such as coeliac disease, hypothyroidism and rickets.
19. The patient and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct.
20. Participation in any other trial of an investigational agent within 30 days prior to Screening.

Ages Eligible for Study 3 Years to 11 Years (Child )

Sexes Eligible for Study All

Accepts Healthy Volunteers No

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.Expand all

 / Collapse allHow is the study designed?

Design Details

Primary Purpose  : Treatment

Allocation  : Randomized

Interventional Model  : Parallel Assignment

Masking  : None (Open Label)

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
Experimental: MOD-4023 low doseOnce weekly subcutaneous injection of long acting r-hGH (MOD-4023)	Drug: MOD-4023Once weekly subcutaneous injection
Experimental: MOD-4023 middle doseOnce weekly subcutaneous injection of long acting r-hGH (MOD-4023)	Drug: MOD-4023Once weekly subcutaneous injection
Experimental: MOD-4023 high doseOnce weekly subcutaneous injection of long acting r-hGH (MOD-4023)	Drug: MOD-4023Once weekly subcutaneous injection
Active Comparator: GenotropinOnce daily subcutaneous injection of Somatropin (r-hGH; Genotropin)	Drug: SomatropinOnce daily subcutaneous injection of GenotropinOther Names:Genotropin

What is the study measuring?

Primary Outcome Measures 

Outcome Measure	Measure Description	Time Frame
Annual Height Velocity	Annual Height Velocity in cm/year measured after 12 months of treatment	12 months of treatment

Secondary Outcome Measures 

Outcome Measure	Measure Description	Time Frame
Height Velocity at 6 Months	Annualized Height Velocity in cm/year measured after 6 months of treatment	After 6 months of treatment
Change in Height Standard Deviation Score (SDS)	Change in height standard deviation score from baseline (compared to normal population of same age group and sex). Height SDS was calculated as height minus reference mean height divided by SD of the reference mean height	After 6 and 12 months of treatment
Change in IGF-1 Standard Deviation Score	Change in IGF-1 standard deviation score from reference population mean of same age group and sex (WHO source). IGF-1 SDS was calculated as IGF-1 result minus reference mean IGF-1 result divided by SD of the reference mean IGF-1 value.	Once monthly on day 4 after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor 

OPKO Health, Inc.

Investigators 

• Principal Investigator:Zvi Zadik, MD,Kaplan Medical Center, Israel

Publications

From PubMed

These publications come from PubMed, a public database of scientific and medical articles. This list is automatically created by ClinicalTrials.gov Identifier (NCT Number), and these articles may or may not be about the study.

• Zelinska N, Iotova V, Skorodok J, Malievsky O, Peterkova V, Samsonova L, Rosenfeld RG, Zadik Z, Jaron-Mendelson M, Koren R, Amitzi L, Raduk D, Hershkovitz O, Hart G. Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children. J Clin Endocrinol Metab. 2017 May 1;102(5):1578-1587. doi: 10.1210/jc.2016-3547.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted 

2012-05-02

First Submitted that Met QC Criteria 

2012-05-03

First Posted (Estimated) 

2012-05-07

Results Reporting Dates

Results First Submitted 

2019-12-12

Results First Submitted that Met QC Criteria 

2020-01-22

Results First Posted 

2020-01-23

Certification/Extension Dates

Certification/Extension First Submitted 

2015-01-08

Certification/Extension First Submitted that Met QC Criteria 

2015-03-12

Certification/Extension First Posted (Estimated) 

2015-04-01

Study Record Updates

Last Update Submitted that met QC Criteria 

2020-01-22

Last Update Posted 

2020-01-23

Last Verified 

2020-01