Vosoritide for Short Stature

Recruiting at 22 trial locations

Overseen By Study Manager

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: BioMarin Pharmaceutical

Must be taking: hGH

Disqualifiers: Systemic disease, Congenital heart disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests vosoritide, a treatment that might help children grow taller. It targets children with Turner syndrome, SHOX deficiency, or Noonan syndrome, conditions that can cause short stature. The study compares three doses of vosoritide with human growth hormone (hGH) to determine which is most effective for increasing growth over six months. Children who have been on hGH for at least a year and aren't experiencing sufficient growth may be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires participants to continue taking their current human growth hormone (hGH) medication for the baseline growth phase and for 2 years if they are in the hGH group.

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

Research has shown that vosoritide is generally safe for children with achondroplasia, a condition affecting bone growth. In these studies, most children experienced no serious side effects, which is encouraging for its potential use in other conditions related to short stature, such as Turner syndrome and Noonan syndrome. Although the treatment remains under testing, these results suggest that vosoritide is usually safe for children. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Vosoritide is unique because it offers a new approach to treating short stature by specifically targeting a growth pathway that is different from traditional methods. Unlike the standard human growth hormone treatments, which aim to increase growth hormone levels, vosoritide directly addresses the underlying genetic causes of short stature by enhancing the natural growth signals in the body. This direct action on the growth plate could potentially result in more effective height gains for individuals with certain growth deficiencies. Researchers are excited about vosoritide because it represents a targeted therapy with the potential to improve outcomes for those who do not respond adequately to existing treatments.

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

Studies have shown that vosoritide can significantly help children with conditions like achondroplasia and hypochondroplasia grow taller. Research indicates that children treated with vosoritide experience faster growth over time. In trials, vosoritide was well-tolerated and led to continued growth improvements for up to six years. This trial will compare different doses of vosoritide with Human Growth Hormone to evaluate their effectiveness. These findings suggest that vosoritide could also help children with Turner syndrome, SHOX deficiency, and Noonan syndrome grow taller by increasing their growth rate. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director, MD, PhD

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for children aged 3-10 (females) or 3-11 (males) with a confirmed diagnosis of Turner syndrome, SHOX deficiency, or Noonan syndrome. They should be in the earliest stage of physical development and have had an inadequate response to human growth hormone treatment which they've been on for at least a year.

Inclusion Criteria

I am between 3 and 9 years old if female, or between 3 and 10 years old if male.

I have a genetic diagnosis of Turner syndrome, SHOX deficiency, or Noonan syndrome.

A height assessment corresponding to a height Z score of ≤ -2.00 SDs in reference to the general population of the same age and sex

Exclusion Criteria

I might need surgery for an unstable condition during the study.

I have Turner syndrome with Y-chromosome material and have had a gonadectomy.

I have had or plan to have surgery to lengthen my limbs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three doses of vosoritide or human growth hormone for 6 months to evaluate growth as measured by AGV

6 months

Extended Treatment

Further evaluation of the efficacy and safety of the vosoritide therapeutic dose compared to hGH over 2 years

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with an analysis of the impact on final adult height (FAH)

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Human Growth Hormone
• Vosoritide

Trial Overview The study tests three doses of Vosoritide against human growth hormone in promoting growth over six months. It aims to determine long-term effectiveness and safety up to final adult height by comparing average growth velocity between treatments.

How Is the Trial Designed?

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

Drug: Vosoritide Dose 3 Injection • Experimental Drug Lyophilized powder for reconstitution

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

Drug: Vosoritide - Dose 2 Injection • Experimental Drug Lyophilized powder for reconstitution

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

Drug: Vosoritide - Dose 1 Injection • Experimental Drug Lyophilized powder for reconstitution

Group IV: Human Growth Hormone Active Control 1 Intervention

Drug: Human Growth Hormone

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

In a phase 3 extension study involving children with achondroplasia, daily treatment with vosoritide led to a significant increase in growth velocity, from 4.26 cm/year at baseline to 5.52 cm/year after two years.

The study found that vosoritide was safe, with no new adverse effects reported, demonstrating its potential as a long-term treatment option for promoting growth in children with achondroplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Savarirayan, R., Tofts, L., Irving, M., et al.[2022]

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]

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 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]

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]

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 (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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39864410/

Real-World Safety and Effectiveness of Vosoritide in ... In clinical trials, vosoritide has shown a positive safety profile and increased height in children with achondroplasia.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666634024004604

Sustained growth-promoting effects of vosoritide in children ... Vosoritide treatment was well tolerated and had sustained growth-promoting effects in children with achondroplasia treated for up to 6 years.

4. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00170-6/fulltext

Vosoritide treatment for children with hypochondroplasia Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been ...

5. academic.oup.com academic.oup.com/jes/article/9/5/bvaf041/8064591

Real-world Outcome of Vosoritide Treatment in Children With ... In a real-world setting, children with ACH showed significant improvements in growth and physical function after 12 months of treatment with vosoritide.

6. 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.

7. pedsendo.org pedsendo.org/clinical-study/vosoritide-for-selected-genetic-causes-of-short-stature/

Vosoritide for Selected Genetic Causes of Short Stature This is a single arm prospective interventional trial of vosoritide, a CNP analog, for the treatment of five genetic causes of short stature.