Vosoritide for Turner Syndrome

Recruiting at 1 trial location

Overseen By Kimberly Boucher, RN

Age: < 18

Sex: Female

Trial Phase: Phase 2

Sponsor: Roopa Kanakatti Shankar, MBBS, MS

Must not be taking: Estrogen, GnRH analogs

Disqualifiers: Growth plate fusion, Malignancy, Y-chromosome, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether vosoritide, a medication that promotes bone cell growth, can enhance growth in girls with Turner syndrome who have short stature. Turner syndrome is a genetic condition in females where part or all of one X chromosome is missing, resulting in shorter height. The trial targets pre-pubertal girls with Turner syndrome who have not responded well to growth hormone therapy or have never tried it. Participants will receive vosoritide through daily injections for a year, and researchers will monitor changes in their growth rate. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that participants stop taking growth hormone or recombinant insulin-like growth factor-1 (IGF-1) at least one week before the screening visit. Other medications like estrogen, certain hormone analogs, and some steroids are also not allowed during the trial.

Is there any evidence suggesting that vosoritide is likely to be safe for humans?

Research has shown that vosoritide is safe for use in conditions similar to Turner syndrome. In children with achondroplasia, another growth-related condition, vosoritide was well-tolerated, and the safety results aligned with existing knowledge about the drug. In studies involving Turner syndrome, early results appear promising, but more time is needed to confirm its long-term safety. Overall, vosoritide seems to be a safe option, but ongoing research will offer more insights into its long-term effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Turner syndrome?

Vosoritide is unique because it targets the underlying growth issues in Turner Syndrome by mimicking a natural protein that helps regulate bone growth. Unlike current treatments that mainly focus on hormone replacement, vosoritide works directly on the growth plates in bones. This new mechanism of action offers the potential to enhance height outcomes beyond what is achievable with existing therapies. Researchers are excited because it opens up a new avenue for improving quality of life for those with Turner Syndrome.

What evidence suggests that vosoritide might be an effective treatment for Turner syndrome?

Research has shown that vosoritide, a treatment similar to a natural body chemical, can help children with Turner syndrome grow faster. In early studies, children who took vosoritide grew more each year than before starting the treatment. Vosoritide helps certain bone cells, called chondrocytes, to grow and multiply. This method has already succeeded in treating achondroplasia, another condition that causes short stature. These early positive results suggest that vosoritide could improve growth in children with Turner syndrome. Participants in this trial will receive vosoritide daily through subcutaneous injection for 12 months. ^{1 2 4 5 6}

Who Is on the Research Team?

Roopa Kanakatti Shankar, MBBS, MS

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for pre-pubertal girls under 11 years old with Turner Syndrome, either not treated with growth hormone or who had a poor response to it. They must be willing to follow study procedures and have a height significantly below average for their age. Girls with fused growth plates, Y-chromosome material without gonadectomy, significant unrelated health issues, allergies to the medication, or recent investigational drug use are excluded.

Inclusion Criteria

Patient height <-2 SDS. All height SDS values are calculated using the CDC growth charts/data tables

Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Subjects under the age of 18 are willing and able to provide assent if required

I am willing and able to follow all study requirements.

Exclusion Criteria

I have Y-chromosome material but have undergone surgery to have female genitalia.

Known or suspected allergy to trial medication, excipients, or related products

I am currently taking growth hormone or IGF-1 treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous injections of vosoritide for 12 months to assess growth velocity and safety

12 months

Monthly visits for safety monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Extension

Participants with a positive response to therapy may continue receiving vosoritide until growth cessation

Until growth cessation

What Are the Treatments Tested in This Trial?

Interventions

• Vosoritide

Trial Overview The trial tests Vosoritide's effectiveness in increasing growth velocity over 12 months in girls with Turner Syndrome who have short stature. It compares their growth rate on Vosoritide against historical data from before treatment. Responders can continue receiving the drug after the initial study period.

How Is the Trial Designed?

Group I: Vosoritide treatment arm Experimental Treatment 1 Intervention

Vosoritide will be administered daily via subcutaneous injection for 12 months using the FDA approved weight-based dosing band strategy for achondroplasia.

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?

Roopa Kanakatti Shankar, MBBS, MS

Lead Sponsor

Trials

1

Recruited

20+

Roopa Kanakatti Shankar

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Inotersen (Tegsedi™) is a second-generation antisense oligonucleotide that effectively inhibits the production of the misfolded transthyretin protein, addressing the underlying cause of hereditary transthyretin amyloidosis (ATTR).

In the Phase III NEURO-TTR study, inotersen demonstrated significant efficacy in stabilizing or improving peripheral neuropathy and enhancing quality of life for patients, marking it as a breakthrough therapy for this previously untreatable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotersen (transthyretin-specific antisense oligonucleotide) for treatment of transthyretin amyloidosis. Benson, MD., Dasgupta, NR., Monia, BP.[2020]

Patisiran is the first approved RNA interference therapy that effectively reduces levels of the amyloidogenic protein TTR, showing a safe clinical profile in early phase studies and significant clinical benefits in a phase III trial involving patients with hereditary transthyretin-mediated amyloidosis (ATTRv).

The treatment led to substantial improvements in polyneuropathy scores and quality of life for patients, and it has been approved for use in Stage I and II ATTRv with polyneuropathy, while its effects on ATTRv with cardiomyopathy are still being studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of patisiran: a viable treatment option for transthyretin-related hereditary amyloidosis. Milani, P., Mussinelli, R., Perlini, S., et al.[2020]

Turner syndrome, characterized by the absence of one X chromosome, leads to significant health risks, including small stature and ovarian failure, necessitating lifelong medical supervision and specialized care.

Recent advancements in treatment include improved fertility options like egg donation and vitrification, as well as enhanced monitoring for cardiovascular issues, particularly aortic dissection, through regular cardiac ultrasounds and MRIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical guideline 'Turner syndrome']. van den Akker, EL., van Alfen, AA., Sas, T., et al.[2022]

In a study of 31 adult patients with Turner's Syndrome, significant differences in final height were observed based on karyotype, indicating that genetic variations may influence clinical outcomes.

The analysis revealed that many patients had additional health issues, such as congenital cardiac and renal malformations, hypercholesterolemia, and abnormal liver function, highlighting the need for comprehensive management strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Turner's syndrome in adult life: case-series and systematic review. Ros, C., Castelo-Branco, C.[2023]

A survey of 155 North American endocrinologists and gynecologists revealed that while 87% felt confident in prescribing hormone replacement therapy (HRT) for adolescents and young adults with Turner syndrome, only half were aware of existing guidelines.

Provider preferences for HRT varied significantly by specialty, with gynecologists less likely to choose hormonal contraceptives and more likely to prefer a higher transdermal estradiol dose, highlighting the need for standardized, evidence-based treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormone Replacement Therapy After Pubertal Induction in Adolescents and Young Adults with Turner Syndrome: A Survey Study. Dowlut-McElroy, T., Kanakatti Shankar, R.[2023]

Turner syndrome, affecting 25-50 per 100,000 females, requires a multidisciplinary approach to care due to its impact on multiple organs throughout life, as highlighted by recent advances in treatment guidelines.

An international consensus meeting led to updated guidelines addressing key areas of care, including growth, cardiovascular health, and hormonal therapy, with formal evaluations of treatment efficacy for conditions like short stature and infertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Gravholt, CH., Andersen, NH., Conway, GS., et al.[2022]

A study of 29 individuals with Turner syndrome (ages 15-26) showed that those receiving standard estrogen doses had normal uterine growth, with uterine length and volume actually larger than in a control group of 292 females without Turner syndrome.

The findings suggest that current international guidelines for estrogen dosing in Turner syndrome are effective, as they support adequate uterine development during pubertal induction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Recommended Estrogen Dosing for Pubertal Induction in Turner Syndrome Results in Normal Uterine Growth. Lindsay Mart, F., Gutmark-Little, I., Streich-Tilles, T., et al.[2023]

Up to 83% of patients with TTR amyloidosis (ATTR) experience lower urinary tract dysfunction, with voiding symptoms being the most common, affecting 34.8-87.5% of patients.

Over 40% of ATTR patients suffer from sexual dysfunction, with erectile dysfunction in men and sexual arousal disorder in women being the most prevalent symptoms, highlighting the need for comprehensive assessment and tailored management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of urinary and sexual dysfunction in hereditary TTR amyloidosis. Bentellis, I., Amarenco, G., Gamé, X., et al.[2020]

In a study using a V30M TTR transgenic mouse model, TTR siRNA treatment effectively cleared TTR deposits from the meninges and brain blood vessels, suggesting a potential therapeutic approach for managing CNS-related complications in familial amyloid polyneuropathy (FAP).

Despite the significant reduction of TTR in the blood, cerebrospinal fluid levels remained unchanged, indicating that TTR siRNA does not disrupt the protective functions of TTR in the central nervous system, which is an important consideration for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficiency of silencing RNA for removal of transthyretin V30M in a TTR leptomeningeal animal model. Gonçalves, P., Martins, H., Costelha, S., et al.[2017]

Hereditary transthyretin-related amyloidosis (ATTRv) is a serious genetic condition that leads to severe nerve and heart problems, but treatments like patisiran and inotersen can significantly reduce the levels of the harmful transthyretin protein, improving patient outcomes.

Both patisiran and inotersen have been shown to slow the progression of neuropathy and enhance quality of life in patients, and they have been approved for use in Germany since August 2018 for specific stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gene therapy options for hereditary transthyretin-related amyloidosis]. Schilling, M.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12544845/

SAT-213 Trial of Vosoritide for Treatment of Short Stature in ... The primary outcomes are change in AGV and height SD from baseline (efficacy) and incidence of adverse events (AEs) (safety). We report on ...

2. 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.

3. innovationdistrict.childrensnational.org innovationdistrict.childrensnational.org/encouraging-early-results-for-vosoritide-in-turner-syndrome/

Encouraging early results for vosoritide in Turner syndrome In the world's first clinical trial of vosoritide for Turner Syndrome, preliminary results show an increase in annualized growth velocity.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05849389

Vosoritide for Short Stature in Turner Syndrome All subjects will be treated with vosoritide for 12 months and will be assessed for safety monitoring and improvement in height outcomes. Annualized growth ...

5. clinicaltrials.eu clinicaltrials.eu/inn/vosoritide/

Vosoritide – Application in Therapy and Current Clinical ... This article explores the ongoing clinical trials investigating the safety and efficacy of vosoritide in treating conditions such as Turner syndrome, SHOX ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06668805

NCT06668805 | A Phase 2 Basket Study of Vosoritide in ... The study is intended to characterize the short-term efficacy and safety of 3 dosing regimens of vosoritide versus hGH. The efficacy and safety of the ...