Clinical trial NCT06668805: 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
Official title: A Phase 2, Randomized, Human Growth Hormone-Controlled, Multicenter, Basket Study of Vosoritide in Children With Turner Syndrome, Short Stature Homeobox-Containing Gene Deficiency, and Noonan Syndrome With an Inadequate Response to Human Growth Hormone. (CANOPY NS, TS, SHOX-D-2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Short Stature Homeobox- Containing Gene SHOX Deficiency
Noonan Syndrome
Turner Syndrome
Keywords: Short Stature
Musculoskeletal Diseases
Bone Diseases
Developmental Endocrine System Diseases Natriuretic Peptide, C-Type
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2024-10-31
Enrollment: 72
Sex: ALL
Minimum age (years): 3
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Participants must be ≥ 3 years old, and \< 10 years old (females) or \< 11 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 ≤ -2.00 SDs in reference to the general population of the same age and sex.
4. Tanner Stage 1, at time of signing the ICF.
5. 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.
6. Are willing to continue on hGH for the Baseline Growth Phase, and for 2 years post randomization if randomized to the hGH arm.
7. Inadequate response to prior hGH treatment.

Exclusion Criteria:

1. 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. 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.

Primary outcomes:
measure: Change from baseline in Annualized Growth Velocity (AGV)
timeFrame: At 6 months
Secondary outcomes:
measure: Change from baseline in Height
timeFrame: 24 months
measure: Change in baseline height Z-score
timeFrame: 24 months
measure: Change in baseline height in AGV
timeFrame: 24 months
measure: Incidence of treatment-emergent adverse events
timeFrame: Until the end of the study, up to 15 years
measure: Change from baseline in height
timeFrame: At 6 months
measure: Change from baseline in height Z-score
timeFrame: At 6 months
measure: Change from baseline in height up to Final Adult Height (FAH)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Change from baseline in height Z-score up to FAH
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Time vosoritide is present at maximum concentration (Tmax)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Maximum vosoritide observed plasma concentration (Cmax)
timeFrame: Every 6 months through he end of the study, up to15 years
measure: Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Elimination half-life of vosoritide (t½)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Apparent clearance of vosoritide (CL/F)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Apparent volume of distribution of vosoritide (Vz/F)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Change from baseline on bone growth biomarkers
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Change from baseline in urine cyclic guanine monophosphate (cGMP)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Change from baseline in serum collagen X marker (CXM)
timeFrame: Every 6 months through the end of the study, up to 15 years
measure: Change from baseline in bone age/chronological age
timeFrame: Every 12 months through the end of the study, up to 15 years
measure: Change from baseline in total body (less head) BMD Z-score
timeFrame: Every 12 months through the end of the study, up to 15 years
measure: Change from baseline in lumbar spine bone mineral density (BMD) Z-score
timeFrame: Every 12 months through the end of the study, up to 15 years
measure: Change from baseline in total body (less head) bone mineral content (BMC)
timeFrame: Every 12 months through the end of the study, up to 15 years
measure: Change from baseline in lumbar spine BMC
timeFrame: Every 12 months through the end of the study, up to 15 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours Children's Hospital, Delaware (Alfred I. Dupont Hospital for Children)
state: Delaware
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Boise
country: United States
facility: St. Luke's Children's Endocrinology and Diabetes
state: Idaho
city: Lexington
country: United States
facility: Kentucky Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: New York Medical College
state: Massachusetts
city: Minneapolis
country: United States
facility: M Health Fairview Pediatric Specialty Clinic - Explorer
state: Minnesota
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Charlotte
country: United States
facility: Atrium Health Carolinas Medical Center
state: North Carolina
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston (UT Health)
state: Texas
city: Angers
country: France
facility: Angers University Hospital Center
state: Maine-et-Loire
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital des Enfants
state: Occitanie
city: Oviedo
country: Spain
facility: Central University Hospital of Asturias
state: Asturias
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD, PhD
role: STUDY_DIRECTOR
References: