Vosoritide for Short Stature

Recruiting at 9 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

Trial Summary

What is the purpose of this trial?

The purpose of this basket study in children with Turner syndrome, SHOX deficiency, and Noonan syndrome is to evaluate the effect of 3 doses of vosoritide versus hGH on growth as measured by AGV after 6 months of treatment. The long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to FAH.

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.

What data supports the effectiveness of the drug Vosoritide for short stature?

Vosoritide has been shown to increase growth velocity in children with achondroplasia, a condition that causes short stature, according to multiple studies. It is the first approved treatment specifically for this purpose, demonstrating its effectiveness in promoting bone growth in affected children. ^{1 2 3 4 5}

How is the drug Vosoritide unique for treating short stature in achondroplasia?

Vosoritide is unique because it is the first approved drug specifically designed to increase growth in children with achondroplasia by targeting the underlying genetic cause. It works by mimicking a natural peptide to counteract the effects of a gene mutation that slows bone growth, and it is administered as a daily injection at home. ^{1 2 3 6 7}

Research Team

Medical Director, MD, PhD

Principal Investigator

BioMarin Pharmaceutical

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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, 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®) 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]

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

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

3. 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]

4. United States 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. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Vosoritide: First Approval. [2022]