Somapacitan vs Norditropin for Growth Disorders

(REAL 8 Trial)

Not currently recruiting at 378 trial locations

Overseen By Novo Nordisk

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must not be taking: Systemic corticosteroids, Inhaled glucocorticoids, Methylphenidate, Sex hormones

Disqualifiers: ADHD, Malignancy, Hepatitis B/C, 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

Compensation: Varies

Number of Visits: 3

Duration: 273 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments for children with growth disorders, including those born small or with conditions like Turner Syndrome, Noonan Syndrome, or idiopathic short stature. It evaluates how a new medicine, somapacitan (a growth hormone therapy), compares to Norditropin®, a treatment some doctors already prescribe. Participants will receive either somapacitan weekly for up to 5.5 years or Norditropin® daily for one year, followed by somapacitan weekly for up to 4.5 years. The trial seeks children who haven't received growth treatments before and have significant growth challenges, such as being notably shorter than peers. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot have had prior growth-promoting therapy, and certain medications affecting growth, like systemic corticosteroids or treatments for ADHD, are not allowed. Thyroid hormone therapy must be stable for 90 days if applicable.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking treatments that affect growth, like certain ADHD medications, or if you are on sex hormones or aromatase inhibitors.

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

Research has shown that somapacitan is generally well-tolerated, with a safety profile similar to other treatments and no major safety issues identified. It is already approved for some patients with growth hormone deficiency, indicating its safety for similar conditions.

Doctors have prescribed Norditropin® for a long time, and it has a well-known safety record, demonstrating its safe use in many patients.

Both treatments in this trial have supporting safety data. Although somapacitan is newer, studies confirm its safety. Norditropin® is already trusted by doctors. Participants can feel confident about the safety of these treatments based on existing research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Somapacitan for growth disorders because it offers a new approach to treatment with its long-acting formulation. Unlike the standard daily injections of growth hormone treatments like Norditropin®, Somapacitan is designed for less frequent dosing, potentially improving convenience and adherence for patients. Additionally, this treatment maintains effective hormone levels over a longer period, which could enhance overall outcomes and quality of life for those with growth disorders.

What evidence suggests that this trial's treatments could be effective for growth disorders?

This trial will compare Somapacitan with Norditropin® for growth disorders. Research has shown that Somapacitan holds promise for aiding children's growth. In earlier studies, children who took Somapacitan grew about 3.4 inches per year on average, similar to the growth seen with daily treatments like Norditropin®. Another study found that Somapacitan matched Norditropin® in boosting growth rates. Norditropin® is already a trusted treatment for growth disorders, and Somapacitan offers a once-a-week option, which might be easier to manage. Both treatments have proven effective in supporting growth in children with conditions like Turner Syndrome, Noonan Syndrome, or idiopathic short stature. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Transparency dept. 2834

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for children who were born small and remain small, or have Turner Syndrome, Noonan Syndrome, or idiopathic short stature. They must not have had growth-promoting therapy before and meet specific criteria related to age, puberty status, BMI, and height. Children with certain medical conditions or on conflicting medications are excluded.

Inclusion Criteria

My son is between 2.5 and 11 years old with small testes.

I, or my legal guardian, have given permission for me to participate in this study.

My son is between 2.5 and 11 years old with small testes.

Exclusion Criteria

Any disorder, which in the investigator's opinion, might jeopardize participant's safety or compliance with the protocol

The participant or the parent/legally acceptable representative is likely to be non-compliant in respect to study conduct, as judged by the investigator

My child has been on high-dose asthma medication for more than a month in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Somapacitan once a week for up to 5.5 years or Norditropin® once a day for 1 year followed by Somapacitan once a week for up to 4.5 years

273 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Extension

Participants in the Norditropin® group transition to Somapacitan for an additional 221 weeks

221 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Norditropin®
• Somapacitan

Trial Overview The study compares somapacitan (a new medicine given once a week) with Norditropin® (an existing treatment taken daily). Over three years, participants will either receive somapacitan the whole time or start with Norditropin® for one year followed by somapacitan for two years. The assignment of treatments is random.

How Is the Trial Designed?

Group I: Somapacitan Experimental Treatment 1 Intervention

Participants will receive Somapacitan for 273 weeks

Group II: Norditropin® Active Control 1 Intervention

Participants will receive Norditropin® for 52 weeks (main treatment period) and Somapacitan for 221 weeks (extension period)

Norditropin® is already approved in United States, European Union for the following indications:

Approved in United States as Norditropin for:

• Pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH)
• Short stature associated with Noonan syndrome
• Short stature associated with Turner syndrome
• Short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years
• Idiopathic Short Stature (ISS)
• Growth failure due to Prader-Willi syndrome (PWS)
• Replacement of endogenous GH in adults with growth hormone deficiency (GHD)

Approved in European Union as Norditropin for:

• Pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH)
• Short stature associated with Noonan syndrome
• Short stature associated with Turner syndrome
• Short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years
• Idiopathic Short Stature (ISS)
• Growth failure due to Prader-Willi syndrome (PWS)
• Replacement of endogenous GH in adults with growth hormone deficiency (GHD)

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Norditropin(R) SimpleXx(TM), a liquid formulation of human growth hormone, significantly improved the ease of injection for 64% of children compared to the traditional freeze-dried version, which may enhance patient compliance in long-term treatment.

The new auto-insertion device, PenMate(TM), was found to be safe and easy to use, with 88% of children preferring it for future treatments, indicating a positive impact on the overall treatment experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device. Müller, J., Skakkebaek, NE., Jacobsen, BB., et al.[2022]

Norditropin® (somatropin) significantly increases height in Japanese children with short stature due to Noonan syndrome, with a greater effect observed at the higher dose of 0.066 mg/kg/day compared to 0.033 mg/kg/day over a 104-week treatment period.

The treatment demonstrated a favorable safety profile, with most adverse events being mild and unlikely related to the medication, and no withdrawals due to adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two doses of Norditropin&#174; (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients. Ozono, K., Ogata, T., Horikawa, R., et al.[2022]

In clinical trials involving 1061 subjects, the varenicline solution nasal spray (VNS) showed a high treatment completion rate of 93.5%, indicating it is well-tolerated despite some adverse events.

Compared to conventional dry eye treatments like cyclosporine and lifitegrast, which had lower completion rates (80% and 91% respectively), VNS appears to be a more favorable option for managing dry eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, adherence and discontinuation in varenicline solution nasal spray clinical trials for dry eye disease. Hauswirth, SG., Kabat, AG., Hemphill, M., et al.[2023]

Beraprost sodium significantly improves exercise capacity in patients with pulmonary arterial hypertension (PAH), with a notable increase in the 6-minute walking distance by an average of 25.1 meters compared to placebo after 12 weeks.

The treatment is particularly effective in patients with primary pulmonary hypertension, showing an even greater improvement of 46.1 meters in walking distance, while drug-related side effects were more common during the initial titration phase but decreased during maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. Galiè, N., Humbert, M., Vachiéry, JL., et al.[2021]

Omidenepag isopropyl (OMDI) significantly reduced intraocular pressure (IOP) in untreated open-angle glaucoma patients, dropping from a baseline of 15.7 mmHg to 13.7 mmHg after 3 months, indicating its efficacy as a first-line treatment.

Switching from prostaglandin F receptor agonists to OMDI in patients already on treatment did not result in significant changes in IOP, suggesting that while OMDI is effective as a new treatment, it may not provide additional benefits when replacing existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newly or switching effect of a selective EP2 agonist on intraocular pressure in Japanese patients with open-angle glaucoma. Ueda, K., Sakata, R., Fujishiro, T., et al.[2022]

Somapacitan, a long-acting growth hormone derivative, demonstrated sustained efficacy in promoting height velocity in children with growth hormone deficiency over a 2-year period, with similar growth rates observed after switching from daily growth hormone treatment.

The treatment was well tolerated with no safety issues reported, and a significant majority (90%) of patients and caregivers preferred the once-weekly somapacitan regimen over daily injections, indicating a favorable patient experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH. Miller, BS., Blair, JC., Rasmussen, MH., et al.[2023]

Bimatoprost ophthalmic solution 0.03% significantly reduced intraocular pressure (IOP) in Japanese patients with normal-tension glaucoma, demonstrating its efficacy in managing this condition.

The treatment was generally well tolerated, with only a few patients discontinuing due to side effects, although some experienced conjunctival hyperemia and eyelash disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bimatoprost ophthalmic solution 0.03% lowered intraocular pressure of normal-tension glaucoma with minimal adverse events. Tsumura, T., Yoshikawa, K., Suzumura, H., et al.[2021]

In a clinical trial with 107 participants suffering from allergic conjunctivitis, bepotastine besilate ophthalmic solution 1.5% significantly reduced ocular itching and tearing compared to placebo 16 hours after administration.

Both concentrations of bepotastine besilate (1.0% and 1.5%) were effective in reducing ocular itching, but only the 1.5% solution showed significant improvement in tearing, while no significant effect was observed on conjunctival redness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged effectiveness of bepotastine besilate ophthalmic solution for the treatment of ocular symptoms of allergic conjunctivitis. Williams, JI., Kennedy, KS., Gow, JA., et al.[2017]

Somapacitan, a long-acting growth hormone derivative, shows increased exposure in patients with kidney or hepatic impairment, indicating that dosage adjustments may be necessary for these individuals.

In trials involving 44 subjects with kidney impairment and 34 with hepatic impairment, no new safety issues were identified, suggesting that somapacitan is well-tolerated even in patients with compromised organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Kidney or Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Somapacitan: Two Open-Label, Parallel-Group Trials. Bentz Damholt, B., Dombernowsky, SL., Dahl Bendtsen, M., et al.[2021]

Somapacitan, a long-acting growth hormone for treating growth hormone deficiency, allows for effective monitoring of insulin-like growth factor-I (IGF-I) levels through reliable linear models that predict mean and peak IGF-I levels based on blood samples taken after dosing.

The study simulated 39,200 IGF-I profiles from 49 patients (26 adults and 23 children) and found that samples taken on day 2 and day 4 after dosing provided the most accurate estimates for peak and mean IGF-I levels, respectively, indicating a robust method for monitoring treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan. Juul Kildemoes, R., Højby Rasmussen, M., Agersø, H., et al.[2021]

In a study of 4,582 children receiving two years of growth hormone treatment, those born small for gestational age (SGA) and with idiopathic short stature (ISS) showed significant height gains, with SGA children experiencing a height standard deviation score (SDS) increase of +1.03, compared to +0.84 for ISS and +0.97 for isolated growth hormone deficiency (IGHD).

The results suggest that early treatment with growth hormone is beneficial, especially in pre-pubertal children, as they exhibited the greatest height increases, indicating that starting treatment early can optimize growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of response to 2-years' growth hormone treatment in children with isolated growth hormone deficiency, born small for gestational age, idiopathic short stature, or multiple pituitary hormone deficiency: combined results from two large observational studies. Lee, PA., Sävendahl, L., Oliver, I., et al.[2022]

During the COVID-19 pandemic, 17% of pediatric patients were switched to Norditropin® growth hormone therapy, with two-thirds of these switches attributed to its ease of use and positive feedback from patients and caregivers.

Clinicians reported that 66% of patients preferred Norditropin® over their previous therapy, highlighting the importance of user-friendly devices and effective training, especially in the context of virtual consultations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicians' Feedback on Patient/Carer Experience After Switching of Growth Hormone Treatment in Pediatric Patients During COVID-19. Blair, J., Warth, K., Suvarna, Y., et al.[2022]

In a 26-week phase 3 trial involving 92 adults with growth hormone deficiency, once-weekly somapacitan was found to be well tolerated, with no significant safety issues or severe injection site reactions reported.

Patients using somapacitan reported significantly higher treatment satisfaction regarding convenience compared to those using the once-daily Norditropin, indicating a preference for the less frequent dosing schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial. Johannsson, G., Feldt-Rasmussen, U., Håkonsson, IH., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40400262/

Efficacy, safety, and insulin-like growth factor I of weekly ... This study aims to evaluate the efficacy and tolerability of somapacitan after 3 years of treatment and 2 years after switch from daily GH in children with GHD.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK599837/

Somapacitan (Sogroya) - NCBI Bookshelf - NIH CDEC concluded that somapacitan may meet some of the needs identified by patients and their caregivers, including comparable growth results to existing ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02616562

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® ...

4. sogroya.com sogroya.com/results-and-safety/for-children.html

Growth Hormone Treatment for Children Children switching to Sogroya® grew ~3.4 inches per year (8.7 cm), on average, at 2 years. These results are from the REAL4 main trial phase ( ...

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/novo-nordisk-sogroya-demonstrates-favorable-outcomes-trial-children-growth-disorders

Novo Nordisk's Sogroya Demonstrates Favorable ... The REAL8 basket study showed Sogroya (somapacitan) was non-inferior to Norditropin (somatropin) in improving yearly growth rate.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761156s005lbl.pdf

SOGROYA (somapacitan-beco) - accessdata.fda.gov The safety and effectiveness of SOGROYA have been established for the treatment of growth failure due to inadequate secretion of endogenous growth hormone (GH) ...

7. novomedlink.com novomedlink.com/growth-related-disorders/products/treatments/sogroya/efficacy-safety/adult-ghd.html

Adult Growth Hormone Deficiency | Sogroya® ... EFFICACY AND SAFETY IN ADULT PATIENTS WITH GHD. See the data on changes from baseline at 34 weeks in truncal fat and body composition with once-weekly Sogroya ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/761156s000lbl.pdf

SOGROYA (somapacitan-beco) - accessdata.fda.gov There are no available data on SOGROYA use in pregnant women; however, published studies with short-acting recombinant growth hormone (rhGH) use in pregnant ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10505532/

Weekly Somapacitan in GH Deficiency: 4-Year Efficacy, ... Somapacitan showed similar efficacy and safety in patients who continued somapacitan treatment and those who switched from daily GH to somapacitan.