A Phase 2 Basket Study of Vosoritide in Children With Turner Syndrome, SHOX Deficiency and Noonan Syndrome With an Inadequate Response to Human Growth Hormone
Phase 2
Recruiting
- Conditions
- Short Stature Homeobox- Containing Gene SHOX DeficiencyNoonan SyndromeTurner Syndrome
- Interventions
- Registration Number
- NCT06668805
- Lead Sponsor
- BioMarin Pharmaceutical
- Brief Summary
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.
- Detailed Description
This is a Phase 2, randomized, active-controlled, multicenter, basket study of vosoritide in children with Turner syndrome, short stature homeobox-containing gene (SHOX) deficiency, or Noonan syndrome who have an inadequate response to human growth hormone (hGH) treatment. 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 vosoritide therapeutic dose will be further evaluated, with a comparison to hGH after 2 years of treatment, and an analysis of the impact of vosoritide on final adult height (FAH).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
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
- A genetically confirmed diagnosis of Turner syndrome, SHOX deficiency or Noonan syndrome.
- A height assessment corresponding to a height Z-score of > -2.00 SDs and ≤ -1.75 SDs (up to 20% of participants)/≤ -2.00 SDs (at least 80% of participants) in reference to the general population of the same age and sex.
- Tanner Stage 1, at time of signing the ICF.
- Have been receiving continuous hGH for the treatment of short stature associated with their condition for a minimum of 1 year immediately prior to enrollment and be receiving a dose of ≥ 0.35 mg/kg weekly, with no weight-based dosing changes in the last 6 months and none planned in the future.
- Are willing to continue on hGH at their current dose for the Baseline Growth Phase, and for 2 years post randomization if randomized to the hGH arm.
- Inadequate response to prior hGH treatment.
Exclusion Criteria
- Participants with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia.
- 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.
- Bone age advanced beyond chronological age by more than 2 years.
- Uncorrected congenital heart disease which places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension,
- Have an unstable condition likely to require surgical intervention during the study.
- 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.
- Previous limb-lengthening surgery, or planned or expected to have limb lengthening surgery during the study period.
- Planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vosoritide Dose 1 - Low Dose Vosoritide Injection Drug: Vosoritide - Dose 1 Injection • Experimental Drug Lyophilized powder for reconstitution Vosoritide Dose 2 - Medium Dose Vosoritide Injection Drug: Vosoritide - Dose 2 Injection • Experimental Drug Lyophilized powder for reconstitution Vosoritide Dose 3- High Dose Vosoritide Injection Drug: Vosoritide Dose 3 Injection • Experimental Drug Lyophilized powder for reconstitution Human Growth Hormone Human Growth Hormone Drug: Human Growth Hormone
- Primary Outcome Measures
Name Time Method Change from baseline in Annualized Growth Velocity (AGV) At 6 months
- Secondary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events Until the end of the study, up to 15 years Incidence of new diagnosis of hypertrophic cardiomyopathy in children with Noonan syndrome Every 12 months through the end of the study, up to 15 years Incidence of cardiac conditions requiring discontinuation of study treatment Every 12 months through the end of the study, up to 15 years Change from baseline in height At 6 months and at 24 months Change from baseline in height Z-score At 6 months and at 24 months Change from baseline in 12-month interval AGV 24 months Change from baseline in upper to lower body segment ratio At 12 and 24 months Change from baseline in arm span to height ratio At 12 and 24 months Change from baseline in height up to Final Adult Height (FAH) Every 6 months through the end of the study, up to 15 years Change from baseline in height Z-score up to FAH Every 6 months through the end of the study, up to 15 years 12-month interval AGV summarized by age and sex up to FAH Every 12 months through the end of the study, up to 15 years Tanner stage over the course of the study Every 6 months through the end of the study, up to 15 years Time vosoritide is present at maximum concentration (Tmax) Every 6 months through the end of the study, up to 15 years Maximum vosoritide observed plasma concentration (Cmax) Every 6 months through he end of the study, up to15 years Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t) Every 6 months through the end of the study, up to 15 years Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞) Every 6 months through the end of the study, up to 15 years Elimination half-life of vosoritide (t½) Every 6 months through the end of the study, up to 15 years Apparent clearance of vosoritide (CL/F) Every 6 months through the end of the study, up to 15 years Apparent volume of distribution of vosoritide (Vz/F) Every 6 months through the end of the study, up to 15 years Change from pre-dose in urine cyclic guanine monophosphate (cGMP) Every 6 months through the end of the study, up to 15 years Change from baseline in serum collagen X marker (CXM) Every 6 months through the end of the study, up to 15 years Change from baseline in bone age/chronological age Every 12 months through the end of the study, up to 15 years Change from baseline in total body (less head) BMD Z-score Every 12 months through the end of the study, up to 15 years Change from baseline in lumbar spine bone mineral density (BMD) Z-score Every 12 months through the end of the study, up to 15 years Change from baseline in total body (less head) bone mineral content (BMC) Every 12 months through the end of the study, up to 15 years Change from baseline in lumbar spine BMC Every 12 months through the end of the study, up to 15 years Change in bone morphology based on whole length lower extremity X-rays Every 6 months through the end of the study, up to 15 years Incidence of bone-related events of special interest (fracture, slipped capital femoral epiphysis and avascular necrosis or osteonecrosis) Throughout study Change from baseline in the physical domain score and total score of the QoLISSY At 24 months Change from baseline in the physical and social domain scores and total score of the PedsQL At 24 months Change from baseline in PGI-S and CaGI-S item scores At 24 months PGI-C and CaGI-C item scores At 24 months Change from baseline in PROMIS-SF Physical Activity score At 24 months Change from baseline in KABC-II NVI scores At 24 months
Trial Locations
- Locations (17)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Children's Medical Center Dallas
🇺🇸Dallas, Texas, United States
Hôpital de la Timone
🇫🇷Marseille, Bouches-du-Rhône, France
IRCCS Istituto Giannina Gaslini
🇮🇹Genova, Genoa, Italy
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Nemours Children's Hospital, Delaware (Alfred I. Dupont Hospital for Children)
🇺🇸Wilmington, Delaware, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
St. Luke's Children's Endocrinology and Diabetes
🇺🇸Boise, Idaho, United States
Kentucky Children's Hospital
🇺🇸Lexington, Kentucky, United States
New York Medical College
🇺🇸Boston, Massachusetts, United States
Scroll for more (7 remaining)Icahn School of Medicine at Mount Sinai🇺🇸New York, New York, United StatesCassie MintzContactcassie.mintz@mssm.edu