A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment

May 7, 2026 updated by: BioMarin Pharmaceutical

A Phase 2, Randomized, Multicenter, Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment

The purpose of this study in children with 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 2, randomized, multicenter, study of vosoritide in children with 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).

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Saint Leonards, New South Wales, Australia, 2065
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
    • Victoria
      • Parkville, Victoria, Australia, 3052
  • Canada
    • Alberta
  • France
    • Bouches-du-Rhône
      • Marseille, Bouches-du-Rhône, France, 13385
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49 933
    • Occitanie
      • Toulouse, Occitanie, France
    • Paris
      • Le Kremlin-Bicêtre, Paris, France, 94270
        • Recruiting
        • South Paris University Hospitals - Bicetre Hospital
        • Contact:
      • Paris, Paris, France, 75019
  • Germany
    • Saarland
      • Homburg, Saarland, Germany, 66421
        • Recruiting
        • Universitätsklinikum des Saarlandes
        • Contact:
          • Tilman Rohrer
          • Phone Number: +49 (0) 68-41-16-2-83-01
  • Italy
    • Florence
      • Florence, Florence, Italy, Firenze
        • Recruiting
        • Azienda Ospedaliero Universitaria - Ospedale Pediatrico Meyer
        • Contact:
    • Genoa
      • Genova, Genoa, Italy, 16147
  • Spain
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spain, 33011
        • Not yet recruiting
        • Central University Hospital of Asturias
        • Contact:
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Childrens Hospital Los Angeles
        • Contact:
      • Orange, California, United States, 92868
        • Recruiting
        • Children's Hospital of Orange County Main Campus - Orange
        • Contact:
    • Colorado
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Nemours Children's Hospital, Delaware (Alfred I. Dupont Hospital for Children)
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
    • Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University School Of Medicine
        • Contact:
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • St. Luke's Children's Endocrinology and Diabetes
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Contact:
          • Carlos Prada
          • Phone Number: 312-227-6120
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Hospital for Children at Indiana University Health
        • Contact:
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Contact:
          • Michael Tansey
          • Phone Number: (319) 356-4443
    • Kentucky
      • Lexington, Kentucky, United States, 40506
        • Recruiting
        • Kentucky Children's Hospital
        • Contact:
    • Massachusetts
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • Recruiting
        • M Health Fairview Pediatric Specialty Clinic - Explorer
        • Contact:
    • New York
      • New York, New York, United States, 10029
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Children's Hospital at Montefiore
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3026
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
          • Gajanthan Muthuvel
          • Phone Number: (513) 636-8444
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Childrens Hospital of Philadelphia
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2578
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75235
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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:

  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. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vosoritide Dose 1 - Low Dose

Drug: Vosoritide - Dose 1 Injection

• Experimental Drug Lyophilized powder for reconstitution
Drug: Vosoritide Injection
Modified recombinant human C-type natriuretic peptide Vosoritide
Experimental: Vosoritide Dose 2 - Medium Dose

Drug: Vosoritide - Dose 2 Injection

• Experimental Drug Lyophilized powder for reconstitution
Drug: Vosoritide Injection
Modified recombinant human C-type natriuretic peptide Vosoritide
Experimental: Vosoritide Dose 3- High Dose

Drug: Vosoritide Dose 3 Injection

• Experimental Drug Lyophilized powder for reconstitution
Drug: Vosoritide Injection
Modified recombinant human C-type natriuretic peptide Vosoritide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in Annualized Growth Velocity (AGV)
Time Frame: At 6 months
At 6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of treatment-emergent adverse events
Time Frame: Until the end of the study, up to 15 years
Until the end of the study, up to 15 years
Change from baseline in height up to Final Adult Height (FAH)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from baseline in height Z-score up to FAH
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Time vosoritide is present at maximum concentration (Tmax)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Maximum vosoritide observed plasma concentration (Cmax)
Time Frame: Every 6 months through he end of the study, up to15 years
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)
Time Frame: Every 6 months through the end of the study, up to 15 years
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-∞)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Elimination half-life of vosoritide (t½)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Apparent clearance of vosoritide (CL/F)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Apparent volume of distribution of vosoritide (Vz/F)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from baseline in serum collagen X marker (CXM)
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from baseline in bone age/chronological age
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Change from baseline in total body (less head) BMD Z-score
Time Frame: Every 12 months through the end of the study, up to 15 years
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
Time Frame: Every 12 months through the end of the study, up to 15 years
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)
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Incidence of new diagnosis of hypertrophic cardiomyopathy in children with Noonan syndrome
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Incidence of cardiac conditions requiring discontinuation of study treatment
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
12-month interval AGV summarized by age and sex up to FAH
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Tanner stage over the course of the study
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from pre-dose in urine cyclic guanine monophosphate (cGMP)
Time Frame: Every 6 months through the end of the study, up to 15 years
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)
Time Frame: Throughout study
Throughout study
Change from baseline in height
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from baseline in height Z-score
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from baseline in 12-month interval AGV
Time Frame: Until the end of the study, up to 15 years
Until the end of the study, up to 15 years
Change from baseline in upper to lower body segment ratio
Time Frame: Until the end of the study, up to 15 years
Until the end of the study, up to 15 years
Change from baseline in arm span to height ratio
Time Frame: Until the end of the study, up to 15 years
Until the end of the study, up to 15 years
Change from baseline in lumbar spine BMC. Change from baseline in lower extremity BMD/BMC [Time Frame: Every 12 months through the end of the study, up to 15 years].
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Change in the growth plates, long bone growth and bone morphology based on whole length lower extremity X-rays [Time Frame: Every 12 months through the end of the study, up to 15 years]
Time Frame: Every 6 months through the end of the study, up to 15 years
Every 6 months through the end of the study, up to 15 years
Change from baseline in the physical domain score and total score of the QoLISSY
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Change from baseline in the physical and social domain scores and total score of the PedsQL
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Change from baseline in PGI-S and CaGI-S item scores
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
PGI-C and CaGI-C item scores
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Change from baseline in PROMIS-SF Physical Activity score
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years
Change from baseline in KABC-II NVI scores
Time Frame: Every 12 months through the end of the study, up to 15 years
Every 12 months through the end of the study, up to 15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BioMarin Pharmaceutical

Investigators

  • Study Director: Medical Director, MD, PhD, BioMarin Pharmaceutical

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 22, 2024

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

September 1, 2041

Study Registration Dates

First Submitted

October 30, 2024

First Submitted That Met QC Criteria

October 30, 2024

First Posted (Actual)

October 31, 2024

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 111-211

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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