Safety and Efficacy Phase 3 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children

Pediatric Growth Hormone Deficiency Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02968004
• Other study ID #: CP-4-006
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: June 2024

Study information

• Verified date: February 2024
• Source: OPKO Health, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 224
• Est. completion date: June 2024
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Pediatric Growth Hormone Deficiency

Intervention

Drug:
• MOD-4023
Once weekly subcutaneous injection using pre-filled pen device.
• Somatropin
Once daily subcutaneous injection of Genotropin using pre-filled pen device.

Locations

Country	Name	City	State
Argentina	Hospital de Ninos de la Santisima Trinidad Cordoba	Córdoba
Argentina	Hospital Materno Infantil San Roque	Paraná	Entre Rios
Australia	John Hunter Children's Hospital	New Lambton Heights	New South Wales
Australia	PM Hospital for Children	Subiaco	Western Australia
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Belarus	Health Institution- 2nd City Pediatric Hospital	Minsk
Bulgaria	MHAT Sveta Marina	Varna
Canada	Centre de recherche du CHU Sainte-Justine	Montréal	Quebec
Colombia	Dexa Diab	Bogotá
Colombia	Uniendo	Bogotá
Colombia	Hospital Pablo Tobon Uribe	Medellín
Georgia	Maritime Hospital JSC	Batumi
Georgia	Vere XXI JSC	Tbilisi
Greece	Aghia Sophia Children's Hospital	Athens
Greece	General Children's Hospital of Athens P&A Kyriakou	Athens
India	Manipal Hospital	Bengaluru	Karnataka
India	Postgraduate Institute of Medical Education and Research	Chandigarh	Punjab
India	Care Hospital	Hyderabad	Telangna
India	Getwell Health & Research Institute	Nagpur	Maharashtra
India	Meditrina Institute of Medical Sciences	Nagpur
India	All India Institute of Medical Sciences	New Delhi
India	Sir Gangaram Hospital	New Delhi
India	Jehangir Clinical Development Centre	Pune	Maharashtra
Israel	Haemek Medical Center	Afula
Israel	Soroka Medical Center	Be'er Sheva
Israel	Assaf Harofeh Medical Center	Be'er Ya'aqov
Israel	Bnei Zion Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Scheider Children's Medical Center	Petach Tikva
Israel	Tel Hashomer Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Re?ovot
Israel	Sourasky Medical Center	Tel Aviv
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	KyungPook National University Hospital	Daegu
Korea, Republic of	Chosun University Hospital	Gwangju
Korea, Republic of	Bundang Cha Hospital	Seongnam	Gyeonggi-do
Korea, Republic of	Severance Hospital	Seoul
Mexico	Hospital Angeles de Puebla	Puebla	Reserva Territorial Atilxcayotl
New Zealand	The Liggins Institute	Grafton	Auckland
New Zealand	Wellington Children's Hospital	Newtown	Wellington
Poland	Uniwersyteckie Centrum Kliniczne in Gdansk	Gdansk
Poland	Centrum Zdrowia Matki Polki	Lódz
Russian Federation	Kazan State Medical Univeristy/Pediatric Republic Clinical Hospital	Kazan	Tatarstan Republic
Russian Federation	Endocrinology Scientific Center	Moscow
Russian Federation	Pediatric City Clinical Hospital/Russian Medical Academy of Continuous Education	Moscow
Russian Federation	Saint Petersburg State Pediatric Medical University	Saint Petersburg
Russian Federation	Bashkirian State Medical University	Ufa	Bashlortostan Republic
Russian Federation	Voronezh State Medical University	Voronezh
Spain	Hospital Josep Trueta	Girona	Cataluna
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital de Navarra	Pamplona	Navarra
Spain	Parc Tauli	Sabadell
Spain	Hospital Universitario de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Miguel Servet	Zaragoza	Aragon
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Ukraine	Institute of Endocrinology and Metabolism/VP Komisarenko of Academy of Medical Science of Ukraine	Kyiv
Ukraine	Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine	Kyiv
Ukraine	Odesa Regional Clinical Children's Hospital	Odesa
Ukraine	Vinnitsa Regional Clinical Highly Specialized Endocrinology Centre	Vinnitsa
Ukraine	Zaporizhzhya Regional Clinical Child Hospital	Zaporizhzhya
United Kingdom	Royal Hospital for Children	Glasgow
United Kingdom	St. George's University Hospital	London
United States	Children's Hospital- Colorado	Aurora	Colorado
United States	St Luke's Children's Specialty Center	Boise	Idaho
United States	Tufts Medical Center	Boston	Massachusetts
United States	Buffalo Children's Hospital	Buffalo	New York
United States	Rocky Mountain Pediatrics	Centennial	Colorado
United States	Children's Hospital of Cincinnati / Cincinnati Center for Growth Disorders	Cincinnati	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Children's Hospital of Iowa	Iowa City	Iowa
United States	Nemours Children's Health System	Jacksonville	Florida
United States	The Diabetes & Obesity Clinical Specialist	Las Vegas	Nevada
United States	University of Miami Medical Center	Miami	Florida
United States	Albert Einstein College of Medicine at Yeshiva University	Mineola	New York
United States	University of Minnesota	Minneapolis	Minnesota
United States	Goryeb Children's Hospital	Morristown	New Jersey
United States	Children's Hospital of Orange County- Children's Clinic	Orange	California
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mary Bridge Children's Hospital & Health Center	Tacoma	Washington
United States	University of Massachusettes	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
OPKO Health, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belarus,  Bulgaria,  Canada,  Colombia,  Georgia,  Greece,  India,  Israel,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Russian Federation,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Device	Proportion of successful single injections out of total number of single injections using the MOD-4023 Pen in the USA	6 weeks
Other	Device	Proportion of successful single injections out of total number of single injections using the MOD-4023 Pen in the USA at Week 1 based on the Observer Assessment Tool (OAT)	1 week
Primary	Annual Height Velocity	Annual Height Velocity in cm. Annual Height Velocity at 12 months is based on the difference between the heights at 12 months and baseline.	52 weeks
Secondary	Height Velocity at 6 Months	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.	After 6 months of treatment
Secondary	Change in Height Standard Deviation Score (SDS)	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.	After 6 and 12 months
Secondary	Change in Bone Maturation (BM)	Annual change in bone age measurements as per Gruelich-Pyle method	52 weeks
Secondary	Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS)	Via central lab analysis	Baseline and at 12 months