Growth Hormone Therapy for Growth Hormone Deficiency

Overseen By Rashida Talib, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Northwell Health

Must be taking: Growth hormone

Disqualifiers: GH resistance, Prader Willi, Turner, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

A prospective, randomized, open-label single-blinded study of 50 subjects with growth hormone deficiency, ages 5 to 15 years in which 25 subjects will initiate rhGH therapy at 0.3mg/kg/week and the remaining 25 subjects will initiate their rhGH treatment at 0.2 mg/kg/week for the first 12 months of treatment. Safety parameters, height velocity, and adult height prediction by bone age determination will be assessed at 4-month intervals for 1 year following the initiation of rhGH therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Somatropin for treating growth hormone deficiency?

Research shows that Omnitrope, a form of Somatropin, is effective in treating growth hormone deficiency in both children and adults, improving growth and quality of life. ^{1 2 3 4 5}

Is growth hormone therapy generally safe for humans?

Growth hormone therapy, including treatments like Omnitrope and Genotropin, has been studied for safety in both children and adults with growth hormone deficiency. Most side effects reported were mild or moderate, and serious issues like diabetes were not observed. Some patients experienced benign (non-cancerous) growths, but these were not linked to the therapy. ^{3 6 7 8 9}

How is the drug Somatropin unique for treating growth hormone deficiency?

Somatropin is a recombinant human growth hormone that mimics the natural hormone in the body, and it is available in various forms like Omnitrope, which has been shown to be safe and effective for long-term use in both children and adults with growth hormone deficiency. It offers different administration options, such as the Norditropin NordiFlex pen, which is designed to be user-friendly and may improve adherence to daily injections. ^{1 2 4 10 11}

Research Team

Benjamin Nwosu, MD

Principal Investigator

NORTHWELL HEALTH, INC.

Eligibility Criteria

This trial is for children aged 5-15 with growth hormone deficiency who are in good health or have no other major illnesses. They must be willing to follow the study rules and take nightly GH injections. Kids with GH resistance, syndromic short stature like Prader Willi or Turner syndrome, cancer, or serious heart, kidney, or liver issues can't join.

Inclusion Criteria

I am willing and able to follow all study rules and attend all appointments.

According to your medical history, you are in good health or have been diagnosed with growth hormone deficiency.

I am between 5 and 15 years old.

Exclusion Criteria

Subjects will be excluded if they have syndromic short stature such as Prader Willi syndrome and Turner syndrome

I do not have growth hormone resistance.

I do not have any other active cancers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rhGH therapy at either 0.3 mg/kg/week or 0.2 mg/kg/week for 12 months

12 months

Visits at 0, 4, 8, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Somatropin

Trial Overview The study tests two different starting doses of growth hormone (Somatropin) in kids: one group gets a higher dose (0.3mg/kg/week), the other a lower dose (0.2 mg/kg/week). Their growth speed and predicted adult height will be checked every four months for a year.

Participant Groups

Group I: Arm 2: Growth hormone 0.3 mg/kg/week Active Control 1 Intervention

Twenty-five subjects will initiate rhGH therapy at 0.3 mg/kg/week for the first 12 months of treatment

Group II: Arm 1: Growth hormone 0.2 mg/kg/week Active Control 1 Intervention

Twenty-five subjects will initiate rhGH therapy at 0.2 mg/kg/week for the first 12 months of treatment

Somatropin is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Genotropin for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease
• Short stature homeobox-containing gene (SHOX) deficiency
• Small for gestational age (SGA) with no catch-up growth

Approved in United States as Humatrope for:

• Growth hormone deficiency
• Turner syndrome
• Idiopathic short stature
• Short stature associated with Noonan syndrome
• Short stature associated with Turner syndrome in pediatric patients whose epiphyses are closed

Approved in Canada as Norditropin for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease
• Short stature homeobox-containing gene (SHOX) deficiency
• Small for gestational age (SGA) with no catch-up growth

Approved in Japan as Nutropin for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease

Approved in Switzerland as Omnitrope for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease
• Short stature homeobox-containing gene (SHOX) deficiency
• Small for gestational age (SGA) with no catch-up growth

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Findings from Research

In a phase III study involving 70 prepubertal children with growth hormone deficiency, long-term treatment with Omnitrope (0.03 mg/kg/day) resulted in significant growth improvements over 4 years, including an average height increase of 31.1 cm.

Omnitrope was found to be safe and well tolerated, with significant increases in serum levels of IGF-1 and IGFBP-3, indicating effective stimulation of growth-related hormones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of the recombinant human growth hormone Omnitrope® in the treatment of Spanish growth hormone deficient children: results of a phase III study. López-Siguero, J., Borrás Pérez, MV., Balser, S., et al.[2013]

The PATRO Adults study is a large, long-term observational study designed to assess the safety and efficacy of somatropin (Omnitrope(®)) in adults with growth hormone deficiency, involving multiple centers across Europe.

This study will provide valuable insights into the long-term effects of Omnitrope(®) on various health factors, including diabetes development, tumor recurrence, and overall quality of life, while monitoring adverse events and safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) for the treatment of adult patients with growth hormone deficiency. Beck-Peccoz, P., Minuto, F., Leal-Cerro, A., et al.[2021]

In a study of 67 Italian patients with growth hormone deficiency, Omnitrope® was found to be effective in improving health markers like insulin-like growth factor-1 levels and body composition over an average treatment duration of 45.4 months.

While 55.2% of patients experienced adverse events, none were deemed related to Omnitrope®, indicating that it is generally safe for long-term use in adults with growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope&#174; in adults with growth hormone deficiency: Italian interim analysis of the PATRO Adults study. Ferone, D., Profka, E., Gasco, V., et al.[2018]

In a Phase IV study involving 103 children aged 6 to 17, Norditropin NordiFlex was found to be significantly easier to use than previous growth hormone therapy devices, with a median ease-of-use score of 7.5 (P < 0.001).

Approximately 64.4% of patients preferred Norditropin NordiFlex, and 41% were able to self-inject, indicating that this device may enhance patient autonomy and improve adherence to growth hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

User assessment of Norditropin NordiFlex(®), a new prefilled growth hormone pen: a Phase IV multicenter prospective study. Tauber, M., Jaquet, D., Jesuran-Perelroizen, M., et al.[2022]

In a 12-month phase 3 clinical trial involving 117 treatment-naïve prepubertal children with pediatric growth hormone deficiency (pGHD), both once-weekly somatrogon and once-daily somatropin significantly improved health-related quality of life (HRQoL) as measured by the QoLISSY questionnaire.

Children aged 7 and older reported greater HRQoL improvements with somatrogon compared to somatropin, suggesting that the once-weekly treatment may offer advantages in perceived quality of life, while parents tended to underestimate these improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Loftus, J., Quitmann, J., Valluri, SR.[2023]

In a study involving 186 children with various growth disturbances, Omnitrope® was found to be well tolerated, with 35.6% of patients reporting adverse events, mostly mild, such as headaches and abdominal pain.

The treatment with Omnitrope® led to significant improvements in height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), indicating its effectiveness in promoting growth in children, consistent with previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope®, a somatropin biosimilar, in children requiring growth hormone treatment: Italian interim analysis of the PATRO Children study. Iughetti, L., Tornese, G., Street, ME., et al.[2018]

The PATRO Children study, involving 1837 patients across 184 sites in 10 European countries, is monitoring the long-term safety and efficacy of somatropin (Omnitrope(®)) in children requiring growth hormone treatment, with initial results showing no confirmed cases of diabetes or malignancies.

Efficacy data from the study are consistent with previous findings, indicating that Omnitrope(®) is safe for use in children, including those with specific conditions like Prader-Willi syndrome, and will provide further insights into its long-term safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) in children requiring growth hormone treatment. Pfäffle, R., Schwab, KO., Marginean, O., et al.[2021]

In a study involving 199 children with growth hormone deficiency, treatment with Genotropin significantly increased height velocity from 3-4 cm/year to about 10 cm/year after 6 to 9 months.

The study found that administering the hormone in 6-7 injections per week resulted in greater height gains (2-3 cm/year more) compared to 3 injections, and the treatment showed low immunogenicity, with only 2% of children developing detectable antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with Genotropin worldwide: an update March 1987. Gunnarsson, R., Wilton, P.[2019]

A study involving 294 patients in the USA and 6206 patients in 13 other countries found that treatment with Omnitrope® (rhGH) is well tolerated, with most adverse events being mild or moderate and no cases of diabetes or hyperglycemia reported.

After 3 years of treatment, both US and international rhGH-naïve patients showed significant improvements in height, with mean height SD scores increasing by +1.25 in the US and +1.35 internationally, indicating the efficacy of Omnitrope® in promoting growth in children with growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of Omnitrope&#174; (somatropin) in PATRO Children: a multi-center, post-marketing surveillance study comparison of US and international cohort data. Backeljauw, P., Kanumakala, S., Loche, S., et al.[2022]

Recombinant human growth hormone remains a key treatment for children with short stature, but new therapies like recombinant IGF-1 and C-type natriuretic peptide (CNP) are emerging as effective alternatives for specific conditions.

Other growth-promoting strategies, such as growth hormone-releasing peptide analogues and gonadotropin-releasing hormone analogues, show promise in enhancing growth and potentially improving final height in children by managing bone age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress on growth promoting therapies other than growth hormone. Xue, C., Fu, J.[2023]

In a study involving 3180 adult patients with growth hormone deficiency followed for up to 12.2 years, growth hormone replacement therapy showed significant improvements in body composition, including reductions in waist circumference and body mass index (BMI).

The long-term use of growth hormone replacement was found to be safe, with no new safety concerns identified, supporting its effectiveness and safety in clinical practice over more than 10 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth hormone replacement in adults: Real-world data from two large studies in US and Europe. Weber, MM., Gordon, MB., Höybye, C., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of the recombinant human growth hormone Omnitrope® in the treatment of Spanish growth hormone deficient children: results of a phase III study. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) for the treatment of adult patients with growth hormone deficiency. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope&#174; in adults with growth hormone deficiency: Italian interim analysis of the PATRO Adults study. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

User assessment of Norditropin NordiFlex(®), a new prefilled growth hormone pen: a Phase IV multicenter prospective study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope®, a somatropin biosimilar, in children requiring growth hormone treatment: Italian interim analysis of the PATRO Children study. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) in children requiring growth hormone treatment. [2021]

8. Sweden pubmed.ncbi.nlm.nih.gov

Clinical experience with Genotropin worldwide: an update March 1987. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of Omnitrope&#174; (somatropin) in PATRO Children: a multi-center, post-marketing surveillance study comparison of US and international cohort data. [2022]

10. China pubmed.ncbi.nlm.nih.gov

Progress on growth promoting therapies other than growth hormone. [2023]

11. Scotland pubmed.ncbi.nlm.nih.gov

Growth hormone replacement in adults: Real-world data from two large studies in US and Europe. [2021]