A Basket Study of Vosoritide in Children With Turner Syndrome, Short Stature Homeobox-Containing Gene Deficiency, and Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
Purpose
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 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.
Conditions
- Short Stature Homeobox- Containing Gene SHOX Deficiency
- Noonan Syndrome
- Turner Syndrome
Eligibility
- Eligible Ages
- Between 3 Years and 11 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participants must be ≥ 3 years old, and < 11 years old (females) or < 12 years old (males), at the time of signing the informed consent form 2. A genetically confirmed diagnosis of Turner syndrome, SHOX deficiency or Noonan syndrome. 3. A height assessment corresponding to a height Z-score of ≤ -1.28 SDs (below the 10th percentile for height) in reference to the general population of the same age and sex. 4. Tanner Stage 1, at time of signing the ICF. 5. Previous or current hGH treatment for short stature associated with their condition. 6. Inadequate growth confirmed with an AGV that is less than age- and sex-matched average stature AGV determined using median heights from CDC growth charts
Exclusion Criteria
- Participants with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia. 2. Diagnosis of systemic disease or condition that may cause short stature other than Turner syndrome, SHOX deficiency, or Noonan syndrome, eg, renal, neoplastic, pulmonary, cardiac, gastrointestinal, immunologic and metabolic disease. 3. Bone age advanced beyond chronological age by more than 2 years. 4. Uncorrected congenital heart disease which places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension, 5. Have an unstable condition likely to require surgical intervention during the study. 6. Evidence of decreased growth velocity (AGV < 1.5 cm/year) as assessed over a period of at least 6 months and growth plate closure assessed using bilateral lower extremity X-rays. 7. Previous limb-lengthening surgery, or planned or expected to have limb lengthening surgery during the study period. 8. Planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Vosoritide Dose 1 - Low Dose |
Drug: Vosoritide - Dose 1 Injection • Experimental Drug Lyophilized powder for reconstitution |
|
|
Experimental Vosoritide Dose 2 - Medium Dose |
Drug: Vosoritide - Dose 2 Injection • Experimental Drug Lyophilized powder for reconstitution |
|
|
Experimental Vosoritide Dose 3- High Dose |
Drug: Vosoritide Dose 3 Injection • Experimental Drug Lyophilized powder for reconstitution |
|
Recruiting Locations
Vanderbilt University Medical Center
Nashville, Tennessee 37232-2578
Nashville, Tennessee 37232-2578
More Details
- Status
- Recruiting
- Sponsor
- BioMarin Pharmaceutical
Detailed Description
This is a Phase 2, randomized, multicenter, basket study of vosoritide in children with Turner syndrome, short stature homeobox-containing gene (SHOX) deficiency, or Noonan syndrome who have inadequate growth during or after human growth hormone (hGH) treatment. The study is intended to characterize the short-term efficacy and safety of 3 dosing regimens of vosoritide. The efficacy and safety of the vosoritide therapeutic dose will be further evaluated, and an analysis of the impact of vosoritide on final adult height (FAH).