Clinical trial NCT02968004: Safety and Efficacy Phase 3 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children
Official title: A Phase 3, Open-label, Randomized, Multicenter, 12 Months, Efficacy and Safety Study of Weekly MOD-4023 Compared to Daily Genotropin - Therapy in Pre-pubertal Children With Growth Hormone Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pediatric Growth Hormone Deficiency
Lead sponsor: OPKO Health, Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-18
Enrollment: 224
Sex: ALL
Minimum age (years): 3
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Main Study Inclusion Criteria:

1. 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.
2. Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak plasma GH level of ≤10 ng/mL.
3. Bone age (BA) is not older than chronological age and should be less than 10 for girls and less than 11 for boys.
4. Without prior exposure to any r-hGH therapy (naïve patients).
5. 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
6. Baseline IGF-I level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1)
7. Normal calculated GFR per updated bedside Schwartz formula for pediatric patients
8. 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
9. Normal 46XX karyotype for girls.
10. Willing and able to provide written informed consent of the parent or legal guardian and written assent from patient

    LT-OLE Inclusion Criteria:
11. Completion of the main study (12 months of treatment) with adequate compliance.
12. Willing and able to provide written informed consent of the parent or legal guardian and written assent from patient
13. Agree to refrain from sexual activity

Main Study Exclusion Criteria:

1. Children with prior history of leukemia, lymphoma, sarcoma or any other forms of cancer.
2. History of radiation therapy or chemotherapy
3. Malnourished children defined as BMI \< -2 SDS for age and sex
4. Children with psychosocial dwarfism
5. Children born small for gestational age (SGA - birth weight and/or birth length \<-2 SDS 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. 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.
9. Chromosomal abnormalities including Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX mutations/deletions and skeletal dysplasias.
10. 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)
11. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking chronically a dose greater than 400 μg/d of inhaled budesonide or equivalent
12. Major medical conditions and/or presence of contraindication to r-hGH treatment.
13. More than one closed epiphyses
14. Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis.
15. Drug, substance, or alcohol abuse.
16. Known hypersensitivity to the components of study medication.
17. Other causes of short stature such as celiac disease, uncontrolled primary hypothyroidism and rickets.
18. Likely non-compliance in respect to study conduct
19. Participation in any other trial of an investigational agent within 30 days prior to consent
20. Study enrollment has been met or study is closed by sponsor prior to completion of screening process.

    LT-OLE Exclusion Criteria:
21. 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)
22. 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.)
23. Positive pregnancy test
24. Unresolved drug related (Genotropin or MOD-4023) SAE from the treatment period as per medical monitor judgement.

Primary outcomes:
measure: Annual Height Velocity
timeFrame: 52 weeks
Secondary outcomes:
measure: Height Velocity at 6 Months
timeFrame: After 6 months of treatment
measure: Change in Height Standard Deviation Score (SDS)
timeFrame: After 6 and 12 months
measure: Change in Bone Maturation (BM)
timeFrame: 52 weeks
measure: Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS)
timeFrame: Baseline and at 12 months
Other outcomes:
measure: Device
timeFrame: 6 weeks
measure: Device
timeFrame: 1 week
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County- Children's Clinic
state: California
city: Aurora
country: United States
facility: Children's Hospital- Colorado
state: Colorado
city: Centennial
country: United States
facility: Rocky Mountain Pediatrics
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Health System
state: Florida
city: Miami
country: United States
facility: University of Miami Medical Center
state: Florida
city: Boise
country: United States
facility: St Luke's Children's Specialty Center
state: Idaho
city: Iowa City
country: United States
facility: Children's Hospital of Iowa
state: Iowa
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusettes
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Las Vegas
country: United States
facility: The Diabetes & Obesity Clinical Specialist
state: Nevada
city: Morristown
country: United States
facility: Goryeb Children's Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Buffalo Children's Hospital
state: New York
city: Mineola
country: United States
facility: Albert Einstein College of Medicine at Yeshiva University
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital of Cincinnati / Cincinnati Center for Growth Disorders
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital & Health Center
state: Washington
city: Paraná
country: Argentina
facility: Hospital Materno Infantil San Roque
state: Entre Rios
city: Córdoba
country: Argentina
facility: Hospital de Ninos de la Santisima Trinidad Cordoba
city: New Lambton Heights
country: Australia
facility: John Hunter Children's Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
state: New South Wales
city: Subiaco
country: Australia
facility: PM Hospital for Children
state: Western Australia
city: Minsk
country: Belarus
facility: Health Institution- 2nd City Pediatric Hospital
city: Varna
country: Bulgaria
facility: MHAT Sveta Marina
city: Montréal
country: Canada
facility: Centre de recherche du CHU Sainte-Justine
state: Quebec
city: Bogotá
country: Colombia
facility: Dexa Diab
city: Bogotá
country: Colombia
facility: Uniendo
city: Medellín
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Batumi
country: Georgia
facility: Maritime Hospital JSC
city: Tbilisi
country: Georgia
facility: Vere XXI JSC
city: Athens
country: Greece
facility: Aghia Sophia Children's Hospital
city: Athens
country: Greece
facility: General Children's Hospital of Athens P&A Kyriakou
city: Bengaluru
country: India
facility: Manipal Hospital
state: Karnataka
city: Nagpur
country: India
facility: Getwell Health & Research Institute
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre
state: Maharashtra
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
state: Punjab
city: Hyderabad
country: India
facility: Care Hospital
state: Telangna
city: Nagpur
country: India
facility: Meditrina Institute of Medical Sciences
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: New Delhi
country: India
facility: Sir Gangaram Hospital
city: Afula
country: Israel
facility: Haemek Medical Center
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Be'er Ya'aqov
country: Israel
facility: Assaf Harofeh Medical Center
city: Haifa
country: Israel
facility: Bnei Zion Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Scheider Children's Medical Center
city: Ramat Gan
country: Israel
facility: Tel Hashomer Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Seongnam
country: Korea, Republic of
facility: Bundang Cha Hospital
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: KyungPook National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Puebla
country: Mexico
facility: Hospital Angeles de Puebla
state: Reserva Territorial Atilxcayotl
city: Grafton
country: New Zealand
facility: The Liggins Institute
state: Auckland
city: Newtown
country: New Zealand
facility: Wellington Children's Hospital
state: Wellington
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne in Gdansk
city: Łódź
country: Poland
facility: Centrum Zdrowia Matki Polki
city: Ufa
country: Russian Federation
facility: Bashkirian State Medical University
state: Bashlortostan Republic
city: Kazan
country: Russian Federation
facility: Kazan State Medical Univeristy/Pediatric Republic Clinical Hospital
state: Tatarstan Republic
city: Moscow
country: Russian Federation
facility: Endocrinology Scientific Center
city: Moscow
country: Russian Federation
facility: Pediatric City Clinical Hospital/Russian Medical Academy of Continuous Education
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical University
city: Voronezh
country: Russian Federation
facility: Voronezh State Medical University
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
state: Aragon
city: Girona
country: Spain
facility: Hospital Josep Trueta
state: Cataluna
city: Pamplona
country: Spain
facility: Hospital de Navarra
state: Navarra
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sabadell
country: Spain
facility: Parc Tauli
city: Santiago De Compostela
country: Spain
facility: Hospital Universitario de Santiago de Compostela
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Kyiv
country: Ukraine
facility: Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine
city: Kyiv
country: Ukraine
facility: Institute of Endocrinology and Metabolism/VP Komisarenko of Academy of Medical Science of Ukraine
city: Odesa
country: Ukraine
facility: Odesa Regional Clinical Children's Hospital
city: Vinnitsa
country: Ukraine
facility: Vinnitsa Regional Clinical Highly Specialized Endocrinology Centre
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya Regional Clinical Child Hospital
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: London
country: United Kingdom
facility: St. George's University Hospital
Study officials:
affiliation: Sponsor GmbH
name: Tony Cruz
role: STUDY_DIRECTOR
References:
citation: Deal CL, Steelman J, Vlachopapadopoulou E, Stawerska R, Silverman LA, Phillip M, Kim HS, Ko C, Malievskiy O, Cara JF, Roland CL, Taylor CT, Valluri SR, Wajnrajch MP, Pastrak A, Miller BS. Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2717-e2728. doi: 10.1210/clinem/dgac220.