Vosoritide for Idiopathic Short Stature

Recruiting at 8 trial locations

Overseen By Trial Specialist

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: BioMarin Pharmaceutical

Must not be taking: Growth promoters

Disqualifiers: Genetic syndromes, Skeletal dysplasias, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests vosoritide, a treatment that could benefit children with idiopathic short stature (unexplained short height). Researchers aim to compare different doses of vosoritide to human growth hormone (hGH) in promoting growth. The study includes multiple groups: some will receive varying doses of vosoritide, others will get hGH, and some will receive a placebo (a non-active treatment). Children who are noticeably shorter than their peers and have not undergone any previous growth treatments might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have previously used a growth-promoting agent, you may not be eligible to participate.

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

Research has shown that vosoritide, also known as Voxzogo, is generally safe for children. It is approved for those with achondroplasia, a condition affecting bone growth. Studies found that vosoritide was well-tolerated, with most participants not experiencing serious side effects. The safety results align with existing knowledge from its use in achondroplasia, confirming its safety. For those considering joining a trial, vosoritide has also been tested in other conditions with positive safety outcomes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about vosoritide because it targets a different mechanism than traditional treatments for idiopathic short stature. Unlike human growth hormone (hGH), which stimulates growth broadly, vosoritide specifically inhibits a protein that slows bone growth, potentially leading to more effective height increase. This targeted approach could offer a more direct way to enhance growth in children with idiopathic short stature, providing a promising alternative to current therapies. With its novel action on bone growth, vosoritide could represent a significant advancement in treating this condition.

What evidence suggests that this trial's treatments could be effective for idiopathic short stature?

Research has shown that vosoritide may help children with certain bone conditions grow taller. One study found that children who took vosoritide for a year grew an average of 6.36 centimeters. Another study reported even more growth over two years, with an average increase of 11.86 centimeters in height. These results suggest that vosoritide could benefit children with idiopathic short stature (ISS). While most research has focused on achondroplasia, the positive growth outcomes indicate its potential for ISS. This trial will compare different doses of vosoritide with a placebo and human growth hormone to evaluate its effectiveness for ISS. ^{1 3 6 7 8}

Who Is on the Research Team?

Medical Director MD

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for children with idiopathic short stature, which means they are significantly shorter than their peers without a known cause. They should have a height Z-score ≤ -2.25 and may have had previous growth treatments. Children with certain genetic conditions causing short stature or those in later stages of puberty are not eligible.

Inclusion Criteria

My physical development is at the earliest puberty stage.

My height is significantly below average for my age and sex.

I have a genetic condition causing short stature, such as Turner syndrome or Noonan syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational

Baseline growth is assessed during a minimum 6-month observational period

6 months

Randomized Treatment

Participants receive randomized treatment with vosoritide or placebo for a minimum of 6 months

6 months

Open-label Treatment

Participants receive open-label vosoritide until near-final adult height or age threshold is reached

Variable (until near-final adult height or age threshold)

Human Growth Hormone Treatment

Participants in the hGH group receive open-label hGH for a minimum of 4 years

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Vosoritide

Trial Overview The study tests the effects of vosoritide injections compared to human growth hormone in children with ISS. Vosoritide's potential to promote growth will be evaluated over multiple doses and against the established treatment of human growth hormone.

How Is the Trial Designed?

Group I: Vosoritide Dose 3 - High Dose Experimental Treatment 1 Intervention

Vosoritide Dose 3 daily injection

Group II: Vosoritide Dose 2 - Medium Dose Experimental Treatment 1 Intervention

Vosoritide Dose 2 daily injection

Group III: Vosoritide Dose 1 - Low Dose Experimental Treatment 1 Intervention

Vosoritide Dose 1 daily injection

Group IV: Human Growth Hormone Active Control 1 Intervention

hGH daily injection

Group V: Placebo Placebo Group 1 Intervention

Placebo daily injection

Vosoritide is already approved in United States for the following indications:

Approved in United States as Voxzogo for:

• To increase linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses
• to increase linear growth in pediatric patients less than 5 years of age with achondroplasia with open epiphyses

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Published Research Related to This Trial

Vosoritide (VOXZOGO®) is a modified C-type natriuretic peptide that effectively treats achondroplasia by inhibiting the overactive FGFR3 gene, which negatively regulates bone growth.

Approved in the EU for patients aged 2 years and older with open epiphyses, vosoritide represents a significant advancement in achondroplasia treatment, with ongoing regulatory reviews in the USA and further clinical development worldwide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosoritide: First Approval. Duggan, S.[2022]

Vosoritide, administered at a recommended dose of 15 μg/kg, was shown to be effective in increasing growth velocity in children with achondroplasia over a 52-week phase III study involving 60 patients, with no significant safety concerns noted.

The pharmacokinetics of vosoritide indicated rapid absorption and consistent exposure without accumulation, and the development of anti-vosoritide antibodies in 42% of patients did not adversely affect growth outcomes or drug exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Chan, ML., Qi, Y., Larimore, K., et al.[2022]

Vosoritide (Voxzogo) has received accelerated approval from the FDA for treating children aged five and older with achondroplasia, a common form of dwarfism.

To ensure safety and prevent hypotensive episodes, children taking vosoritide should consume a meal and 240 to 300 mL of fluid within an hour before administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Treats Pediatric Achondroplasia. Aschenbrenner, DS.[2023]

Vosoritide is the first approved treatment for achondroplasia, and parents of children using it reported a strong motivation to manage the daily injectable treatment for potential long-term benefits, such as improved height and independence.

The study highlighted the need for better support and consistent training for families, as experiences with treatment initiation varied significantly, impacting their ability to manage the treatment effectively at home.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parents' Experience of Administering Vosoritide: A Daily Injectable for Children with Achondroplasia. NiMhurchadha, S., Butler, K., Argent, R., et al.[2023]

In a study of 39 short pubertal boys treated for one year, letrozole was found to be more effective in increasing levels of luteinizing hormone (LH) and testosterone while lowering estradiol and IGF-1 compared to anastrozole.

Although both treatments resulted in similar growth velocities, anastrozole showed a greater increase in predicted adult height (PAH) after one year, suggesting it may have a more favorable impact on height potential in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole vs anastrozole for height augmentation in short pubertal males: first year data. Neely, EK., Kumar, RB., Payne, SL., et al.[2018]

Voxzogo (vosoritide) is the first drug approved by the FDA and EMA specifically for treating achondroplasia, a leading cause of dwarfism, marking a significant advancement in addressing this rare condition.

Despite the risk of decreased blood pressure as a severe adverse event, the benefits of Voxzogo in fulfilling an unmet medical need for patients with achondroplasia led to its accelerated approval in the U.S. as a treatment for a rare pediatric disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update. Simran, ., S, KDS., Dushantrao, SC., et al.[2023]

Vosoritide is the first approved therapy specifically designed to increase growth velocity in children with achondroplasia, and early experiences from experts indicate a generally positive reception in clinical practice.

Effective management of vosoritide treatment requires multidisciplinary support, patient education on administration, and monitoring for adherence, as these factors significantly influence treatment outcomes and patient satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice. Semler, O., Cormier-Daire, V., Lausch, E., et al.[2023]

In a phase 2 trial involving 75 children with achondroplasia aged 0-59 months, vosoritide was found to have a mild adverse event profile, primarily consisting of transient injection-site reactions, indicating it is generally safe for this age group.

After 52 weeks of treatment, children receiving vosoritide showed a slight increase in height Z score compared to those on placebo, suggesting potential efficacy in promoting growth in young children with achondroplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial. Savarirayan, R., Wilcox, WR., Harmatz, P., et al.[2023]

Achondroplasia, the most common form of dwarfism, is caused by a mutation in the FGFR3 gene that leads to increased inhibition of cartilage formation, resulting in characteristic phenotypic features.

Vosoritide, a modified version of C-type natriuretic peptide (CNP) with a longer half-life, has been shown in clinical trials to significantly increase growth velocity in children with achondroplasia before their growth plates fuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vosoritide in the treatment of achondroplasia. Paton, DM.[2022]

Citations

1. investors.biomarin.com investors.biomarin.com/news/news-details/2025/BioMarin-Presents-New-Data-for-VOXZOGO-vosoritide-in-Children-with-Achondroplasia-and-Other-Skeletal-Conditions-at-Two-International-Endocrinology-Meetings/default.aspx

BioMarin Presents New Data for VOXZOGO® (vosoritide) ... Children who received VOXZOGO had a significant reduction in the magnitude of tibial bowing compared to children who received placebo.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06382155

NCT06382155 | A Phase 2 Study of Vosoritide in Children ... The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to ...

3. rarediseaseadvisor.com rarediseaseadvisor.com/news/real-world-studies-demonstrated-vosoritides-growth-benefits-achondroplasia/

Real-World Data Support Efficacy of Vosoritide in Children ... Those treated for 24 months exhibited even greater growth, with an average height gain of 11.86 cm and a Z-score improvement of 1.15. These ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9625806/

OR18-5 A Prospective Clinical Trial of Vosoritide ... 14 subjects have initiated on vosoritide, and 10 completed 6 months of therapy. Median increase in AGV was 3.9 cm/yr (IQR 2.2, 4.6). The two subjects with NPR2 ...

5. prnewswire.com prnewswire.com/news-releases/biomarin-presents-real-world-evidence-further-supporting-safety-and-efficacy-of-voxzogo-vosoritide-in-children-with-achondroplasia-at-the-european-society-for-paediatric-endocrinology-espe-meeting-2024-302307377.html

BioMarin Presents Real-World Evidence Further ... Among 143 participants treated with VOXZOGO for 12 months, the average height increase was 6.36 centimeters (cm), with a height Z-score ...

6. investors.biomarin.com investors.biomarin.com/news/news-details/2024/New-Data-for-BioMarins-VOXZOGO-vosoritide-for-Multiple-Growth-Related-Conditions-in-Children-Presented-at-Pediatric-Endocrine-Society-PES-Annual-Meeting/default.aspx

New Data for BioMarin's VOXZOGO® (vosoritide) ... Investigator-Sponsored Phase 2 Study Demonstrated Positive Results in Children with Noonan Syndrome, Idiopathic Short Stature and Other ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04219007

Vosoritide for Selected Genetic Causes of Short Stature This study will enroll patients with short stature in selected genetic categories and will follow them for a 6 month observation period.

8. withpower.com withpower.com/trial/vosoritide-for-idiopathic-short-stature-47f8e

Vosoritide for Idiopathic Short Stature Is vosoritide safe for humans? Vosoritide, also known as Voxzogo, has been approved for use in children with achondroplasia and is generally considered safe, ...