Vosoritide for Idiopathic Short Stature

Recruiting at 7 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

Trial Summary

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.

What data supports the effectiveness of the drug Vosoritide (Voxzogo) for idiopathic short stature?

Vosoritide has been shown to significantly increase growth velocity in children with achondroplasia, a condition that also causes short stature. This suggests it may be effective for other types of short stature, like idiopathic short stature, although direct evidence for this specific use is not provided. ^{1 2 3 4 5}

Is vosoritide safe for humans?

Vosoritide, also known as Voxzogo, has been approved for use in children with achondroplasia and is generally considered safe, but it can cause a decrease in blood pressure, which is a serious side effect. This risk is outweighed by the benefits for those with achondroplasia, according to regulatory agencies. ^{1 2 4 6 7}

How is the drug vosoritide unique for treating idiopathic short stature?

Vosoritide is unique because it is a daily injectable drug originally developed to treat achondroplasia, a specific form of dwarfism, by targeting a genetic mutation that affects bone growth. It works by restoring normal bone growth through a mechanism that inhibits the overactive signaling pathways caused by this mutation. ^{1 2 6 8 9}

What is the purpose of this trial?

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 human growth hormone (hGH), in children with idiopathic short stature (ISS).

Research Team

Medical Director MD

Principal Investigator

BioMarin Pharmaceutical

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 (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]

References

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

Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update. [2023]

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

Letrozole vs anastrozole for height augmentation in short pubertal males: first year data. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

Efficacy of vosoritide in the treatment of achondroplasia. [2022]

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

Vosoritide: First Approval. [2022]

7. England 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. [2023]

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

New Drug Treats Pediatric Achondroplasia. [2023]

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

Parents' Experience of Administering Vosoritide: A Daily Injectable for Children with Achondroplasia. [2023]