Treatment for short stature in girls with Turner syndrome

Vosoritide for Treatment of Short Stature in Girls With Turner Syndrome

This study is testing if a new treatment called vosoritide can help pre-pubertal girls with Turner syndrome grow taller over a year.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 3 Years to 11 Years
• Sex: Female
• Sponsor: Children's National Research Institute (Academic / other)
• Locations: 1 site (Washington D.C., District of Columbia)
• Trial ID: NCT05849389 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of vosoritide, a C-type natriuretic peptide analog, in increasing growth velocity in pre-pubertal girls diagnosed with Turner syndrome and short stature. Participants will be treated with vosoritide for 12 months, and their growth outcomes will be monitored and compared to their growth velocity prior to treatment. The study aims to enroll girls who are either new to growth hormone therapy or have had a poor response to it. Safety assessments will also be conducted throughout the trial.

Who should consider this trial

Good fit: Ideal candidates for this study are pre-pubertal girls aged 3 to under 11 years with a confirmed diagnosis of Turner syndrome and short stature.

Not a fit: Patients who are post-pubertal or have not been diagnosed with Turner syndrome will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve growth outcomes for girls with Turner syndrome, enhancing their overall quality of life.

How similar studies have performed: While growth hormone therapy has been the standard treatment, this approach using vosoritide is novel and has not been extensively tested in this specific population.

Eligibility criteria

Inclusion Criteria:

1. 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. Also, subjects under the age of 18 are willing and able to provide assent (if required) after the nature of the study has been explained and prior to performance of any research-related procedure.
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Age \>3 years 0 days AND \<10 years 364 days
4. Pre-pubertal defined as Tanner Stage 1 breasts in females.
5. Patient height \<-2 SDS. All height SDS values are calculated using the CDC growth charts/data tables.
6. Patients must have a confirmed diagnosis of Turner Syndrome based on a karyotype with a minimum of 30 cells or on a chromosomal microarray. Subjects with Turner Syndrome mosaicism (such as a 46,XX/45,X karyotype) must have a minimum of 10% mosaicism of 45,X cell line in order to participate in the study.
7. Subjects must either be naïve to growth hormone or have a poor response to growth hormone therapy defined as either:

   1. Subjects completed at least one year of treatment with GH and first year height velocity (HV) below -1 SD according to the National Cooperative Growth Study TS 1st year response to growth hormone height velocity curve.
   2. Subjects receiving GH for more than a year with AGV in the last 6 months \< 50%ile for US girls for age/sex). Subjects meeting this criterion are no longer showing catch up growth and may benefit from an alternative form of therapy.

Exclusion Criteria:

1. Growth plate fusion - Defined as a bone age via the Greulich and Pyle method of 13 years. These patients have limited remaining growth potential.
2. Concomitant treatment with growth hormone or recombinant insulin-like growth factor-1 (IGF-1). Patients may have been previously treated with growth hormone or IGF-1 therapy. If the patient is currently on one of these therapies, they will be required to discontinue at least 1 week prior to the screening visit. That decision will be deferred to their treating clinical endocrinologists in conjunction with the patient's guardians. We anticipate that only patients who are having a poor response to their therapy will be interested in enrolling in the current study as there is no rationale for a patient who is receiving growth hormone therapy and having a positive response to enroll in the current study.
3. Prior or concomitant treatment with any form of estrogen, gonadotropin-releasing hormone (GnRH) analog, aromatase inhibitor or oxandrolone
4. History of any type of malignancy
5. Subjects known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia
6. Chronic medical condition known to affect growth including but not limited to:

   A. Cystic fibrosis B. Diabetes C. Inflammatory Bowel Disease D. Untreated Celiac Disease - If a subject has been diagnosed with celiac disease and has been on a gluten free diet for \>12 months and has a tissue transglutaminase antibody within the normal range at screening, then they are eligible for the trial.

   E. Asthma requiring a daily inhaled steroid dose \> 400 micrograms of inhaled budesonide per day or equivalent F. Taking daily oral glucocorticoids for any reason G. Note - Attention Deficit hyperactivity Disorder (ADHD) treated with a stimulant and treated hypothyroidism with a normal thyroid stimulating hormone (TSH) will NOT exclude the subject from participating in the trial. Subjects on either stimulant medication or thyroid hormone replacement must be on a stable dose for 3 months prior to the screening visit.

   H. Congenital heart disease which places the subject at increased risk of an adverse cardiac outcome in the setting of hypotension including but not limited to: hypertrophic cardiomyopathy, aortic stenosis with peak gradient \>50mmHg, severe aortic regurgitation (defined as pressure half time \>500ms by echocardiogram), coronary insufficiency, or any anatomy with a need for an afterload reducing agent. Any patient with baseline abnormalities on echocardiogram will be reviewed with a pediatric cardiologist for appropriateness for inclusion in the study.
7. Malnutrition - Defined as a BMI \<5th percentile (CDC growth charts)
8. Any clinically significant abnormality on screening tests as determined by the principal investigator. Abnormal screening labs may be repeated up to 3 months after the screening visit. If those labs are normal on repeat, the subject may proceed into the trial.
9. Known or suspected allergy to trial medication, excipients, or related products
10. The receipt of any investigational drug within 90 days prior to this trial

Where this trial is running

Washington D.C., District of Columbia

• Children's National Hospital — Washington D.C., District of Columbia, United States (Recruiting)

Study contacts

• Principal investigator: Roopa Kanakatti Shankar, MBBS, MS — Children's National Research Institute
• Study coordinator: Roopa Kanakatti Shankar, MBBS, MS

Conditions Turner Syndrome; Short Stature; Turner syndrome; Vosoritide