Safety and Efficacy Study of MOD-4023 to Treat Children With Growth Hormone Deficiency

NCT03874013 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CP-4-009
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 46

Brief Summary

Treatment of children with growth failure due to growth hormone deficiency (GHD). Primary • To evaluate the efficacy and safety of weekly MOD-4023 administration compared to daily Genotropin® administration in Japanese pre-pubertal children with GHD. Secondary • To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of three different doses of MOD-4023 in Japanese pre-pubertal children with GHD.

Conditions

Growth Hormone Deficiency

Outcome Measures

Primary Outcomes (1)

• Annual Height Velocity (HV) After 12 Months

  Annual Height Velocity in cm/year after 12 months of treatment.

  12 months

Secondary Outcomes (3)

• Height Velocity at 6 Months

  6 months

• Change in Height Standard Deviation Score (SDS) Compared to Baseline After 12 Months

  12 months

• Change in Bone Maturation (BM) After 12 Months

  12 months

Other Outcomes (1)

• Biochemical

  Baseline, Visit 6 (Month 3), Visit 7 (Month 6), Visit 8 (Month 9) and Visit 9 (12 months)

Study Arms (2)

MOD-4023 Treatment Arm

EXPERIMENTAL

MOD-4023 (investigational treatment): weekly MOD-4023 SC injections for 12 months; initially over the first 6 weeks, MOD-4023 will be administered in 3 stepwise escalating doses (0.25 mg/kg/week, 0.48 mg/kg/week and 0.66 mg/kg/week), each for two weeks sequentially. For the remaining 46 weeks, patients will continue to receive MOD-4023 at a dose of 0.66 mg/kg/week.

Drug: MOD-4023

Genotropin Treatment Arm

ACTIVE COMPARATOR

Genotropin® (reference treatment): daily Genotropin® (0.025 mg/kg/day).

Drug: Genotropin

Interventions

MOD-4023 DRUG

MOD-4023 is a long-acting modified recombinant human growth hormone (r-hGH) which utilizes C-terminal peptide (CTP) technology. It will be provided as a solution for injection containing 20 or 50 mg/mL MOD-4023 in a multi-dose disposable pre-filled PEN. MOD-4023 will be administered as a SC injection once weekly, using a delivery device.

Also known as: Somatrogon

MOD-4023 Treatment Arm

Genotropin DRUG

Genotropin® is dispensed in a 2-chamber cartridge. The front compartment contains recombinant somatropin, glycine, mannitol, sodium dihydrogen phosphate anhydrous and disodium phosphate anhydrous. The rear compartment contains m-Cresol and mannitol in water for injections. A delivery device (Genotropin®) will be used for daily (evening/bedtime) SC administration of Genotropin® into the region of the upper arms, buttocks, thighs or abdomen (8 locations). Injection sites should be rotated. Dose regimen for Genotropin®: 0.025 mg/kg/day (or 0.175 mg/kg/w divided equally to 7 injections over a week).

Genotropin Treatment Arm

Eligibility Criteria

• Age: 3 Years - 11 Years
• Gender Eligibility Details: Pre-pubertal child aged ≥ 3 years old, and not yet 10 years for girls (9 years and 364 days) or not yet 11 years for boys (10 years and 364 days), on the date of ICF signature.
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pre-pubertal child aged ≥ 3 years old, and not yet 10 years for girls (9 years and 364 days) or not yet 11 years for boys (10 years and 364 days), on the date of ICF signature, with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone deficiency.
• Confirmed diagnosis of GHD by 2 different types of GH provocation tests (standardized on growth foundation data): defined as a peak serum GH level of ≤ 6.0 ng/mL or ≤ 16 ng/mL when conducting GHRP-2 provocation test.
• Prior local laboratory results will be accepted subject to pre-approval by the study medical monitor and if the tests were conducted as specified in the protocol.
• 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.
• Height SD score ≤ -2.0 at screening
• Impaired height velocity defined as:
• Annualized height velocity (HV) below the 25th percentile for CA (HV \< -0.7 SDS) and gender according to the local primary care provider standard.
• BMI must be within ±2 SDS of mean BMI for the chronological age and sex.
• Baseline IGF-1 level of at least 1 SDS below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤ -1) according to the central laboratory reference values. A single re-test will be allowed (subject to discussion with the study medical monitor) if all other criteria are met.
• Normal creatinine levels according to common practice reference ranges per age.
• 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 to ICF signing
• Normal 46 XX karyotype for girls.
• Willing and able to provide written informed consent of the parent or legal guardian of the patient and written assent from pediatric patients (when applicable based on age and Japan regulation).

You may not qualify if:

• 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 suspected psychosocial dwarfism by the discretion of the investigator
• Children born small for gestational age (SGA - birth weight and/or birth length \< -2 SDS for gestational age)
• Presence of anti-hGH antibodies at screening
• 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.
• Children with diabetes mellitus
• Chromosomal abnormalities including Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX (short stature homeobox) mutations/deletions and skeletal dysplasia's, with the exception of septo-optic dysplasia.
• Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, sex steroids, with the exception of ADHD drugs or hormone replacement therapies (thyroxin, hydrocortisone, desmopressin \[DDAVP\])
• Children requiring glucocorticoid therapy (e.g. for asthma) that are taking chronically a dose greater than 400 µg/d of inhaled budesonide or equivalent as provided in Appendix J.
• Major medical conditions and/or presence of contraindication to r-hGH treatment.
• Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis.
• Drug substance or alcohol abuse.
• Known hypersensitivity to the components of study medication.

Sponsors & Collaborators

• OPKO Health, Inc.: lead

Study Sites (46)

Aichi Medical University Hospital

Nagakute, Aichi-ken, 480-1195, Japan

Location

Seirei Sakura Citizen Hospital

Sakura, Chiba, 285-8765, Japan

Location

Hospital of the University of Occupational and Environmental Health

Kitakyushu, Fukuoka, 807-8556, Japan

Location

Gunma University Hospital

Maebashi, Gunma, 371-8511, Japan

Location

Fukuyama City Hospital

Fukuyama, Hiroshima, 721-8511, Japan

Location

National Hospital Organization Kure Medical Center & Chugoku Cancer Center

Kure, Hiroshima, 737-0023, Japan

Location

Onomichi General Hospital

Onomichi, Hiroshima, 722-8508, Japan

Location

Hokkaido P.W.F.A.C. Asahikawa-Kosei General Hospital

Asahikawa, Hokkaido, 078-8211, Japan

Location

Asahikawa Medical University Hospital

Asahikawa, Hokkaido, 078-8510, Japan

Location

KKR Sapporo Medical Center

Sapporo, Hokkaido, 062-0931, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Takahashi Clinic

Kobe, Hyōgo, 657-0846, Japan

Location

Takarazuka City Hospital

Takarazuka, Hyōgo, 665-0827, Japan

Location

St. Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

National Hospital Organization Minami Kyoto Hospital

Jōyō, Kyoto, 610-0013, Japan

Location

East Japan Railway Company Sendai Branch Office JR Sendai Hospital

Sendai, Miyagi, 980-8508, Japan

Location

National University Corporation Tohoku University Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Igarashi childrens clinic

Sendai, Miyagi, 981-3203, Japan

Location

Oita University Hospital

Yufu, Oita Prefecture, 879-5593, Japan

Location

Osaka Women's and Children's Hospital

Izumi, Osaka, 594-1101, Japan

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Saitama Medical University Hospital

Iruma-Gun, Saitama, 350-0495, Japan

Location

Saitama Medical Center

Kawagoe, Saitama, 350-8550, Japan

Location

Shimane University Hospital

Izumo, Shimane, 693-8501, Japan

Location

Tokyo Metropolitan Childrens Medical Center

Fuchū, Tokyo, 183-8561, Japan

Location

National Center for Child Health and Development

Setagaya-Ku, Tokyo, 157-8535, Japan

Location

Keio University Hospital

Shinjuku, Tokyo, 160-8582, Japan

Location

Teikyo University Hospital

tabashi City, Tokyo, 173-8606, Japan

Location

Tottori University Hospital

Yonago, Tottori, 683-8504, Japan

Location

Akita University Hospital

Akita, 010-8543, Japan

Location

Fukuoka Children's Hospital

Fukuoka, 813-0017, Japan

Location

Gifu University Hospital

Gifu, 501-1194, Japan

Location

Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital

Hiroshima, 730-8518, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Miyazaki Prefectural Miyazaki Hospital

Miyazaki, 880-8510, Japan

Location

Arakawa Children's Clinic

Nagano, 381-0025, Japan

Location

Nara Prefecture General Medical Center

Nara, 630-8054, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, 951-8520, Japan

Location

Okayama Saiseikai General Hospital Outpatient Center

Okayama, 700-0013, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, 701-1192, Japan

Location

Osaka City General Hospital

Osaka, 534-0021, Japan

Location

Osaka City University Hospital

Osaka, 545-8586, Japan

Location

Saitama Childrens Medical Center

Saitama, 330-8777, Japan

Location

Saitama City Hospital

Saitama, 336-8522, Japan

Location

Shizuoka Childrens Hospital

Shizuoka, 420-8660, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Related Publications (1)

• Horikawa R, Tanaka T, Hasegawa Y, Yorifuji T, Ng D, Rosenfeld RG, Hoshino Y, Okayama A, Ebata N, Hosoi M, Nakamuta S, Gomez R, Pastrak A, Castellanos O. Efficacy and safety of once-weekly somatrogon following up to 4 years of treatment in Japanese children with growth hormone deficiency: results from an open-label extension of a phase 3 study. Endocr J. 2025 Oct 31. doi: 10.1507/endocrj.EJ24-0625. Online ahead of print.

  PMID: 41183961 DERIVED

MeSH Terms

Conditions

Dwarfism, Pituitary

Interventions

MOD-4023; somatrogon; Human Growth Hormone

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: OPKO Health Inc
• Organization: OPKO Health Inc

contact@opko.com

3055754100

Study Officials

• Reiko Horikawa, M.D, Ph. D.

  National Center for Child Health and Development

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: March 14, 2019
• Study Start: December 7, 2017
• Primary Completion: March 6, 2020
• Study Completion: March 6, 2020
• Last Updated: August 12, 2021
• Results First Posted: August 12, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (46)