Safety and Efficacy Phase 3 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children
- Conditions
- Pediatric Growth Hormone Deficiency
- Interventions
- Registration Number
- NCT02968004
- Lead Sponsor
- OPKO Health, Inc.
- Brief Summary
This will be an open-label, randomized, multicenter, efficacy and safety study of weekly MOD-4023 compared to daily Genotropin therapy in pre-pubertal children with growth hormone deficiency.
- Detailed Description
The study will consist of a 12 month, open-label, randomized, active controlled, parallel group study comparing the efficacy and safety of weekly MOD-4023 to daily growth hormone (GH), Genotropin. After 12 months, subjects will have the option to enter the long term open-label extension.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 224
-
Pre-pubertal children aged ≥3 years , and not yet 11 years for girls or not yet 12 years for boys with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone deficiency.
-
Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak plasma GH level of ≤10 ng/mL.
-
Bone age (BA) is not older than chronological age and should be less than 10 for girls and less than 11 for boys.
-
Without prior exposure to any r-hGH therapy (naïve patients).
-
Impaired height and height velocity defined as:
- Annualized height velocity (HV) below the 25th percentile for CA (HV < -0.7 SDS) and gender according to sponsor calculator
- The interval between 2 height measurements should be at least 6 months, but should not exceed 18 months prior to inclusion
-
Baseline IGF-I level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1)
-
Normal calculated GFR per updated bedside Schwartz formula for pediatric patients
-
Children with multiple hormonal deficiencies must be on stable replacement therapies (no change in dose) for other hypothalamo-pituitary-organ axes for at least 3 months prior ICF signing
-
Normal 46XX karyotype for girls.
-
Willing and able to provide written informed consent of the parent or legal guardian and written assent from patient
LT-OLE Inclusion Criteria:
-
Completion of the main study (12 months of treatment) with adequate compliance.
-
Willing and able to provide written informed consent of the parent or legal guardian and written assent from patient
-
Agree to refrain from sexual activity
Main Study
-
Children with prior history of leukemia, lymphoma, sarcoma or any other forms of cancer.
-
History of radiation therapy or chemotherapy
-
Malnourished children defined as BMI < -2 SDS for age and sex
-
Children with psychosocial dwarfism
-
Children born small for gestational age (SGA - birth weight and/or birth length <-2 SDS for gestational age)
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Presence of anti-hGH antibodies at screening
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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.
-
T2 and T1 diabetic patients, who in the opinion of the investigator are not receiving standard of care treatment or are non-compliant with their prescribed treatment or who are in poor metabolic control.
-
Chromosomal abnormalities including Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX mutations/deletions and skeletal dysplasias.
-
Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, or sex steroids, with the exception of ADHD drugs or hormone replacement therapies (thyroxin, hydrocortisone, desmopressin)
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Children requiring glucocorticoid therapy (e.g. for asthma) that are taking chronically a dose greater than 400 μg/d of inhaled budesonide or equivalent
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Major medical conditions and/or presence of contraindication to r-hGH treatment.
-
More than one closed epiphyses
-
Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis.
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Drug, substance, or alcohol abuse.
-
Known hypersensitivity to the components of study medication.
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Other causes of short stature such as celiac disease, uncontrolled primary hypothyroidism and rickets.
-
Likely non-compliance in respect to study conduct
-
Participation in any other trial of an investigational agent within 30 days prior to consent
-
Study enrollment has been met or study is closed by sponsor prior to completion of screening process.
LT-OLE Exclusion Criteria:
-
Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, or sex steroids, with the exception of ADHD drugs or HRT (thyroxin, hydrocortisone, desmopressin)
-
Change in medical condition during the treatment period (such as, but not limited to, development of a serious inter-current critical illness, a severe adverse drug reaction, etc.)
-
Positive pregnancy test
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Unresolved drug related (Genotropin or MOD-4023) SAE from the treatment period as per medical monitor judgement.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MOD-4023 MOD-4023 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023) Genotropin Somatropin Once daily subcutaneous injection of Somatropin (r-hGH; Genotropin)
- Primary Outcome Measures
Name Time Method Annual Height Velocity 52 weeks Annual Height Velocity in cm. Annual Height Velocity at 12 months is based on the difference between the heights at 12 months and baseline.
- Secondary Outcome Measures
Name Time Method Height Velocity at 6 Months After 6 months of treatment Height velocity in cm measured after 6 months of treatment. Annualized Height velocity after 6 months is calculated based on the difference between the heights at 6 months and baseline.
Change in Height Standard Deviation Score (SDS) After 6 and 12 months Change in height Standard Deviation Score (SDS) after 6 and 12 months is calculated based on the difference between the heights at 6 and 12 months and baseline.
Change in Bone Maturation (BM) 52 weeks Annual change in bone age measurements as per Gruelich-Pyle method
Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) Baseline and at 12 months Via central lab analysis
Trial Locations
- Locations (81)
Manipal Hospital
🇮🇳Bengaluru, Karnataka, India
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
University of Massachusettes
🇺🇸Worcester, Massachusetts, United States
Children's Hospital of Iowa
🇺🇸Iowa City, Iowa, United States
Dexa Diab
🇨🇴Bogotá, Colombia
General Children's Hospital of Athens P&A Kyriakou
🇬🇷Athens, Greece
Meditrina Institute of Medical Sciences
🇮🇳Nagpur, India
Hospital de Navarra
🇪🇸Pamplona, Navarra, Spain
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne in Gdansk
🇵🇱Gdańsk, Poland
Zaporizhzhya Regional Clinical Child Hospital
🇺🇦Zaporizhzhya, Ukraine
St Luke's Children's Specialty Center
🇺🇸Boise, Idaho, United States
Getwell Health & Research Institute
🇮🇳Nagpur, Maharashtra, India
Jehangir Clinical Development Centre
🇮🇳Pune, Maharashtra, India
Health Institution- 2nd City Pediatric Hospital
🇧🇾Minsk, Belarus
Maritime Hospital JSC
🇬🇪Batumi, Georgia
Vere XXI JSC
🇬🇪Tbilisi, Georgia
Buffalo Children's Hospital
🇺🇸Buffalo, New York, United States
Care Hospital
🇮🇳Hyderabad, Telangna, India
Centre de recherche du CHU Sainte-Justine
🇨🇦Montréal, Quebec, Canada
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Hospital Angeles de Puebla
🇲🇽Puebla, Reserva Territorial Atilxcayotl, Mexico
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Bnei Zion Medical Center
🇮🇱Haifa, Israel
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Odesa Regional Clinical Children's Hospital
🇺🇦Odesa, Ukraine
Voronezh State Medical University
🇷🇺Voronezh, Russian Federation
Scheider Children's Medical Center
🇮🇱Petach Tikva, Israel
Bundang Cha Hospital
🇰🇷Seongnam, Gyeonggi-do, Korea, Republic of
The Liggins Institute
🇳🇿Grafton, Auckland, New Zealand
All India Institute of Medical Sciences
🇮🇳New Delhi, India
Tel Hashomer Medical Center
🇮🇱Ramat Gan, Israel
Assaf Harofeh Medical Center
🇮🇱Be'er Ya'aqov, Israel
Endocrinology Scientific Center
🇷🇺Moscow, Russian Federation
Institute of Endocrinology and Metabolism/VP Komisarenko of Academy of Medical Science of Ukraine
🇺🇦Kyiv, Ukraine
Vinnitsa Regional Clinical Highly Specialized Endocrinology Centre
🇺🇦Vinnitsa, Ukraine
Hospital Josep Trueta
🇪🇸Girona, Cataluna, Spain
Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine
🇺🇦Kyiv, Ukraine
Royal Hospital for Children
🇬🇧Glasgow, United Kingdom
Wellington Children's Hospital
🇳🇿Newtown, Wellington, New Zealand
Hospital Miguel Servet
🇪🇸Zaragoza, Aragon, Spain
Children's Hospital of Cincinnati / Cincinnati Center for Growth Disorders
🇺🇸Cincinnati, Ohio, United States
PM Hospital for Children
🇦🇺Subiaco, Western Australia, Australia
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Children's Hospital- Colorado
🇺🇸Aurora, Colorado, United States
Children's Hospital of Orange County- Children's Clinic
🇺🇸Orange, California, United States
Nemours Children's Health System
🇺🇸Jacksonville, Florida, United States
Rocky Mountain Pediatrics
🇺🇸Centennial, Colorado, United States
University of Miami Medical Center
🇺🇸Miami, Florida, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Goryeb Children's Hospital
🇺🇸Morristown, New Jersey, United States
The Diabetes & Obesity Clinical Specialist
🇺🇸Las Vegas, Nevada, United States
Hospital de Ninos de la Santisima Trinidad Cordoba
🇦🇷Córdoba, Argentina
Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Hospital Pablo Tobon Uribe
🇨🇴Medellín, Colombia
Uniendo
🇨🇴Bogotá, Colombia
Aghia Sophia Children's Hospital
🇬🇷Athens, Greece
Sir Gangaram Hospital
🇮🇳New Delhi, India
Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, Punjab, India
KyungPook National University Hospital
🇰🇷Daegu, Korea, Republic of
Chosun University Hospital
🇰🇷Gwangju, Korea, Republic of
Centrum Zdrowia Matki Polki
🇵🇱Łódź, Poland
Bashkirian State Medical University
🇷🇺Ufa, Bashlortostan Republic, Russian Federation
Saint Petersburg State Pediatric Medical University
🇷🇺Saint Petersburg, Russian Federation
Pediatric City Clinical Hospital/Russian Medical Academy of Continuous Education
🇷🇺Moscow, Russian Federation
St. George's University Hospital
🇬🇧London, United Kingdom
Haemek Medical Center
🇮🇱Afula, Israel
Kazan State Medical Univeristy/Pediatric Republic Clinical Hospital
🇷🇺Kazan, Tatarstan Republic, Russian Federation
Albert Einstein College of Medicine at Yeshiva University
🇺🇸Mineola, New York, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mary Bridge Children's Hospital & Health Center
🇺🇸Tacoma, Washington, United States
Hospital Materno Infantil San Roque
🇦🇷Paraná, Entre Rios, Argentina
MHAT Sveta Marina
🇧🇬Varna, Bulgaria
John Hunter Children's Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
Parc Tauli
🇪🇸Sabadell, Spain
Hospital Universitario de Santiago de Compostela
🇪🇸Santiago De Compostela, Spain
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan