About this trial
Turner syndrome (TS) is characterized by a missing whole or part of the second sex chromosome in a phenotypic female, resulting in short stature due to haploinsufficiency of the short-stature homeobox-containing (SHOX) gene. Growth hormone (GH) is an approved therapy for this condition, although not associated with GH deficiency, and benefits are modest. Vosoritide, a C-type natriuretic peptide (CNP) analog, targets chondrocytes within the growth plate leading to increased cell proliferation and hypertrophy. We hypothesize that patients with TS and short stature will respond to vosoritide treatment leading to increased growth velocity. This study will enroll pre-pubertal girls with TS who are either naïve to GH or have had a poor response to GH therapy. All subjects will be treated with vosoritide for 12 months and will be assessed for safety monitoring and improvement in height outcomes. Annualized growth velocity (AGV) on vosoritide will be compared to AGV in the 6-18 months prior to initiation of vosoritide based on historical data available in the medical record. Subjects with a positive response to therapy will be given the option to continue in the extension phase of the study during which they will continue to receive vosoritide until growth cessation.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Stated willingness to comply with all study procedures and availability for the duration of the study
Age >3 years 0 days AND <10 years 364 days
Pre-pubertal defined as Tanner Stage 1 breasts in females.
Disqualifiers
Growth plate fusion - Defined as a bone age via the Greulich and Pyle method of 13 years. These patients have limited remaining growth potential.
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.
Prior or concomitant treatment with any form of estrogen, gonadotropin-releasing hormone (GnRH) analog, aromatase inhibitor or oxandrolone
History of any type of malignancy
Trial design
Single group
Treatments tested in this trial
Vosoritide
DrugVosoritide administered daily via subcutaneous injection for 12 months using the FDA approved weight-based dosing band strategy for achondroplasia.
Treatment groups
Trial outcomes
Primary outcomes
Incidence of treatment-emergent adverse events
Number of treatment-emergent adverse events or serious adverse events per study participant
Change from baseline in annualized growth velocity
To evaluate the change from baseline in annualized growth velocity after 12 months of daily subcutaneous injections of vosoritide
Change from baseline in age-sex standardized height standard deviation score
To evaluate the change from baseline in age-sex standardized height standard deviation score (SDS) after 12 months of daily subcutaneous injections of vosoritide
Secondary outcomes
Changes in seated height ratio
To evaluate the seated height ratio as a measure of body proportions compared to baseline after daily subcutaneous injections of vosoritide
Changes in arm span minus standing height
To evaluate the arm span minus standing height as a measure of body proportion compared to baseline after daily subcutaneous injections of vosoritide
Change in Bone Age
To evaluate changes from baseline in bone age/chronological age after 12 months of daily subcutaneous injections of vosoritide
Sponsors and contacts
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Roopa Kanakatti Shankar, MBBS, MS
Lead sponsor
Children's National Research Institute
Sponsor institution