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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a growth hormone treatment called somatropin for children with growth hormone deficiency, a condition where the body produces insufficient growth hormone, resulting in slower growth. Researchers compare two different dosage levels to determine which one better improves growth over a year. They will monitor participants for growth progress and overall treatment safety. Children aged 5 to 15, diagnosed with growth hormone deficiency and able to handle nightly injections, are suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that somatropin, a type of growth hormone treatment, can cause side effects. Common side effects include pain, redness, or swelling at the injection site. More serious concerns include a 30% higher risk of death compared to the general population.

Somatropin is typically used for individuals who do not naturally produce enough growth hormone. As this treatment is in the later stages of research, more information is available about its safety and potential risks. It is crucial to discuss any concerns with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Somatropin for growth hormone deficiency because it offers a more tailored dosing approach. Unlike other treatments that might have a one-size-fits-all dosage, Somatropin in this trial is administered in specific doses of either 0.2 mg/kg/week or 0.3 mg/kg/week, providing flexibility to optimize patient outcomes. This personalized dosing could potentially improve growth responses in children, offering a significant advantage over current therapies. Additionally, the treatment aims to maintain effectiveness over a full year, which could enhance long-term management of the condition.

What is the effectiveness track record for Somatropin in treating growth hormone deficiency?

Research has shown that somatropin effectively treats growth hormone deficiency. Studies have found that children taking somatropin grow faster and approach their expected height. This treatment is generally safe and has side effects similar to other growth hormone treatments. Previous trials demonstrated that both weekly and daily doses of growth hormone, such as somatropin, aid in children's growth. Overall, the evidence supports somatropin as a reliable method to help children with growth hormone deficiency achieve a more typical height. ^{6 7 8 9 10}

Who Is on the Research Team?

Benjamin Nwosu, MD

Principal Investigator

NORTHWELL HEALTH, INC.

Are You a Good Fit for This Trial?

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.

You must submit a signed and dated consent form.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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 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 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]

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]

Citations

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Developments in administration of growth hormone treatment

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We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) ...

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NCT02616562 | Investigating Efficacy and Safety of Once- ...

The aim of the trial is to investigate efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® ...

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hhs.texas.gov

hhs.texas.gov/sites/default/files/documents/oct-2023-durb-agenda-item4q.pdf

Growth Hormone

adverse maternal or fetal outcomes, but historical data for somatropin have not identified a drug- associated risk of major birth defect ...

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Ongoing safety review of Recombinant Human Growth ...

The investigators report a 30% increased risk of death with recombinant human growth hormone therapy compared to the general population.

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Safety & Side Effects

Side effects included injection site reactions, such as pain, redness/swelling, inflammation, bleeding, scarring, lumps, or rash.

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Somatropin, e-coli derived (subcutaneous route)

Somatropin injection is used to treat growth hormone deficiency (inability to produce enough growth hormone), chronic kidney disease, idiopathic short stature.