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

NCT ID: NCT02968004

Last Updated: 2025-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2024-05-31

Brief Summary

This is 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 consists 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.

Conditions

Pediatric Growth Hormone Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MOD-4023

Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)

Group Type: EXPERIMENTAL

MOD-4023

Intervention Type: DRUG

Once weekly subcutaneous injection using pre-filled pen device.

Genotropin

Once daily subcutaneous injection of somatropin (r-hGH; Genotropin)

Group Type: ACTIVE_COMPARATOR

Somatropin

Intervention Type: DRUG

Once daily subcutaneous injection of Genotropin using pre-filled pen device.

Interventions

MOD-4023

Once weekly subcutaneous injection using pre-filled pen device.

Intervention Type: DRUG

Somatropin

Once daily subcutaneous injection of Genotropin using pre-filled pen device.

Intervention Type: DRUG

Other Intervention Names

Somatrogon; Genotropin

Eligibility Criteria

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-1 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.

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.

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.

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OPKO Health, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tony Cruz

Role: STUDY_DIRECTOR

Sponsor GmbH

Locations

Health Institution- 2nd City Pediatric Hospital

Minsk, , Belarus

MHAT Sveta Marina

Varna, , Bulgaria

Children's Hospital of Orange County- Children's Clinic

Orange, California, United States

Children's Hospital- Colorado

Aurora, Colorado, United States

Rocky Mountain Pediatrics

Centennial, Colorado, United States

Nemours Children's Health System

Jacksonville, Florida, United States

University of Miami Medical Center

Miami, Florida, United States

St Luke's Children's Specialty Center

Boise, Idaho, United States

Children's Hospital of Iowa

Iowa City, Iowa, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Massachusettes

Worcester, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

The Diabetes & Obesity Clinical Specialist

Las Vegas, Nevada, United States

Goryeb Children's Hospital

Morristown, New Jersey, United States

Buffalo Children's Hospital

Buffalo, New York, United States

Albert Einstein College of Medicine at Yeshiva University

Mineola, New York, United States

Children's Hospital of Cincinnati / Cincinnati Center for Growth Disorders

Cincinnati, Ohio, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Mary Bridge Children's Hospital & Health Center

Tacoma, Washington, United States

Hospital Materno Infantil San Roque

Paraná, Entre Ríos Province, Argentina

Hospital de Ninos de la Santisima Trinidad Cordoba

Córdoba, , Argentina

John Hunter Children's Hospital

New Lambton Heights, New South Wales, Australia

Children's Hospital at Westmead

Westmead, New South Wales, Australia

PM Hospital for Children

Subiaco, Western Australia, Australia

Centre de recherche du CHU Sainte-Justine

Montreal, Quebec, Canada

Dexa Diab

Bogotá, , Colombia

Uniendo

Bogotá, , Colombia

Hospital Pablo Tobon Uribe

Medellín, , Colombia

Maritime Hospital JSC

Batumi, , Georgia

Vere XXI JSC

Tbilisi, , Georgia

Aghia Sophia Children's Hospital

Athens, , Greece

General Children's Hospital of Athens P&A Kyriakou

Athens, , Greece

Manipal Hospital

Bengaluru, Karnataka, India

Getwell Health & Research Institute

Nagpur, Maharashtra, India

Jehangir Clinical Development Centre

Pune, Maharashtra, India

Postgraduate Institute of Medical Education and Research

Chandigarh, Punjab, India

Care Hospital

Hyderabad, Telangna, India

Meditrina Institute of Medical Sciences

Nagpur, , India

All India Institute of Medical Sciences

New Delhi, , India

Sir Gangaram Hospital

New Delhi, , India

Haemek Medical Center

Afula, , Israel

Soroka Medical Center

Beersheba, , 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

Petah Tikva, , Israel

Tel Hashomer Medical Center

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

Hospital Angeles de Puebla

Puebla City, Reserva Territorial Atilxcayotl, Mexico

The Liggins Institute

Grafton, Auckland, New Zealand

Wellington Children's Hospital

Newtown, Wellington Region, New Zealand

Uniwersyteckie Centrum Kliniczne in Gdansk

Gdansk, , Poland

Centrum Zdrowia Matki Polki

Lodz, , Poland

Bashkirian State Medical University

Ufa, Bashlortostan Republic, Russia

Kazan State Medical Univeristy/Pediatric Republic Clinical Hospital

Kazan', Tatarstan Republic, Russia

Endocrinology Scientific Center

Moscow, , Russia

Pediatric City Clinical Hospital/Russian Medical Academy of Continuous Education

Moscow, , Russia

Saint Petersburg State Pediatric Medical University

Saint Petersburg, , Russia

Voronezh State Medical University

Voronezh, , Russia

Bundang Cha Hospital

Seongnam-si, Gyeonggi-do, South Korea

Inje University Busan Paik Hospital

Busan, , South Korea

KyungPook National University Hospital

Daegu, , South Korea

Chosun University Hospital

Gwangju, , South Korea

Severance Hospital

Seoul, , South Korea

Hospital Miguel Servet

Zaragoza, Aragon, Spain

Hospital Josep Trueta

Girona, Catalonia, Spain

Hospital de Navarra

Pamplona, Navarre, Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Parc Tauli

Sabadell, , Spain

Hospital Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Taipei Veterans General Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine

Kyiv, , Ukraine

Institute of Endocrinology and Metabolism/VP Komisarenko of Academy of Medical Science 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, , Ukraine

Royal Hospital for Children

Glasgow, , United Kingdom

St. George's University Hospital

London, , United Kingdom

Countries

United States; Argentina; Australia; Belarus; Bulgaria; Canada; Colombia; Georgia; Greece; India; Israel; Mexico; New Zealand; Poland; Russia; South Korea; Spain; Taiwan; Ukraine; United Kingdom

References

Gomez R, Khadilkar V, Shembalkar J, Chu DM, Ko CW, Wajnrajch MP, Wang R. Post hoc subgroup analysis of Asian children with paediatric GHD from the global phase 3 efficacy and safety study of once-weekly somatrogon vs. once-daily somatropin. J Pediatr Endocrinol Metab. 2024 May 9;37(6):525-531. doi: 10.1515/jpem-2023-0512. Print 2024 Jun 25.

Reference Type: DERIVED

PMID: 38717038 (View on PubMed)

Loftus J, Quitmann J, Valluri SR. Health-related quality of life in pre-pubertal children with pediatric growth hormone deficiency: 12-month results from a phase 3 clinical trial of once-weekly somatrogon versus once-daily somatropin. Curr Med Res Opin. 2024 Feb;40(2):175-184. doi: 10.1080/03007995.2023.2290623. Epub 2024 Jan 24.

Reference Type: DERIVED

PMID: 38053515 (View on PubMed)

Gomez R, Lamoureux R, Turner-Bowker DM, Loftus J, Maghnie M, Miller BS, Polak M, Yaworsky A. Physician experience with once-weekly somatrogon versus once-daily rhGH regimen in pediatric patients with growth hormone deficiency: a cross-sectional survey of physicians from the global phase 3 study. Front Endocrinol (Lausanne). 2023 Oct 17;14:1254424. doi: 10.3389/fendo.2023.1254424. eCollection 2023.

Reference Type: DERIVED

PMID: 37955005 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35405011 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CP-4-006

Identifier Type: -

Identifier Source: org_study_id