Vosoritide for Turner syndrome | SHOX deficiency | Noonan syndrome

Stratification factors

• Condition (Turner syndrome, SHOX deficiency, Noonan syndrome)
• Past versus current human growth hormone (hGH) treatment

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 2. A genetically confirmed diagnosis of Turner syndrome, SHOX deficiency or Noonan syndrome."}
• {"criterion_text":"- 3. A height assessment corresponding to a height Z-score of ≤ -1.28 SDs (below the 10th percentile in height) in reference to the general population of the same age and sex."}
• {"criterion_text":"- 4. Tanner Stage 1, at time of signing the ICF."}
• {"criterion_text":"- 5. Previous or current hGH for the treatment of short stature associated with their condition"}
• {"criterion_text":"- 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

• {"criterion_text":"- 1. Participants with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 3. Bone age advanced beyond chronological age by more than 2 years."}
• {"criterion_text":"- 4. Uncorrected congenital heart disease which places the participant at increased risk of adverse cardiac outcome in the setting of hypotension."}
• {"criterion_text":"- 5. Have an unstable condition likely to require surgical intervention during the study."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 7. Previous limb-lengthening surgery, or planned or expected to have limb-lengthening surgery during the study period."}
• {"criterion_text":"- 8. Planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in AGV at 6 months","definition_or_measurement_approach":"Change from baseline in AGV (annualized growth velocity) at 6 months. AGV referenced in trial documents and inclusion criteria; inadequate growth confirmed using AGV determined using median heights from CDC growth charts."}

Secondary endpoints

• {"endpoint_text":"- 1. Change from baseline in height and height Z score at 6 months","definition_or_measurement_approach":"Change from baseline in height and height Z-score at 6 months (standard anthropometric measurements / Z-score calculations)."}
• {"endpoint_text":"- 2. Incidence of treatment-emergent adverse events, and results of laboratory and imaging assessments, over the course of the study","definition_or_measurement_approach":"Incidence of TEAEs collected over course of study; laboratory and imaging assessments as per schedule (no further detail provided in JSON)."}
• {"endpoint_text":"- 3. Incidence of new diagnosis of hypertrophic cardiomyopathy in children with Noonan syndrome; Incidence of cardiac conditions requiring discontinuation of study treatment","definition_or_measurement_approach":"Incidence assessed during study; cardiac parameters evaluated (secondary objective notes measurement by echocardiography)."}
• {"endpoint_text":"- 4. Change from baseline in height, height Z-score, and 12-month internal AGV over the course of the study","definition_or_measurement_approach":"Change from baseline in height, height Z-score and 12-month interval AGV summarized during study visits."}
• {"endpoint_text":"- 5. Change from baseline in upper to lower body segment ratio over the course of the study; Change from baseline in arm span to height, ratio over the course of the study","definition_or_measurement_approach":"Anthropometric ratios measured at scheduled visits and compared to baseline."}
• {"endpoint_text":"- 6. Change from baseline in height at each visit up to FAH; Change from baseline in height Z-score at each visit up to FAH; 12-month interval AGV summarized by age and sex up to FAH","definition_or_measurement_approach":"Repeated height and Z-score measurements at each visit up to final adult height (FAH); 12-month AGV intervals summarized by age and sex."}
• {"endpoint_text":"- 7. Tanner stage over the course of the study","definition_or_measurement_approach":"Assessment of Tanner stage at scheduled visits."}
• {"endpoint_text":"- 8. PK parameters (eg, Tmax, Cmax, AUC0-t, AUC0-inf, t1/2, CL/F, and Vz/F)","definition_or_measurement_approach":"Pharmacokinetic sampling to determine parameters such as Tmax, Cmax, AUC0-t, AUC0-inf, t1/2, CL/F and Vz/F."}
• {"endpoint_text":"- 9. Change from pre-dose at prespecified timepoints in urine cGMP; Change from baseline at prespecified timepoints in serum CXM","definition_or_measurement_approach":"Biomarker sampling at prespecified timepoints for urine cGMP (pre-dose changes) and serum CXM (change from baseline)."}
• {"endpoint_text":"- 10. Change from baseline in bone age/chronological age at prespecified timepoints","definition_or_measurement_approach":"Bone age assessments at prespecified timepoints compared to chronological age and baseline."}
• {"endpoint_text":"- 11a. Change from baseline in bone mineralization based on the following, as measured by DXA: • total body (less head) BMD Z-score, • lumbar spine BMD Z-score, • total body (less head) BMC, • lumbar spine BMC, • lower extremity BMD/BMC","definition_or_measurement_approach":"DXA measurements to assess BMD Z-scores and BMC at specified sites."}
• {"endpoint_text":"- 11b. Change in the growth plates (ie, monitoring for closure), long bone growth and bone morphology in X-rays of the lower extremities (bilateral, whole length); Incidence of bone-related events of special interest (fracture, slipped capital femoral epiphysis and avascular necrosis or osteonecrosis)","definition_or_measurement_approach":"Bilateral whole-length lower extremity X-rays to monitor growth plate status, long bone growth and morphology; adverse bone events tracked."}
• {"endpoint_text":"- 12. Change from baseline in the physical domain score and total score of the QoLISSY; Change from baseline in the physical and social domain scores and total score of the PedsQL; Change from baseline in PGI-S and CaGI S item scores; PGI-C and CaGI-C item scores; Change from baseline in PROMIS-SF Physical Activity score","definition_or_measurement_approach":"Patient- and caregiver-reported outcome instruments (QoLISSY, PedsQL, PGI-S/C, CaGI-S/C, PROMIS-SF) administered per schedule; change from baseline evaluated."}
• {"endpoint_text":"- 13. Change from baseline in KABC-II NVI scores","definition_or_measurement_approach":"KABC-II NVI cognitive assessment scores compared to baseline."}
• {"endpoint_text":"- 14. (Listed as secondary endpoint 6 earlier numbering) (see full secondary endpoints list)","definition_or_measurement_approach":"Other secondary endpoints are measured as specified in the protocol and include repeated anthropometrics, PK/PD, biomarker and imaging assessments."}

Methods

• Facebook ads / digital social media (patient-directed digital advertising) — country-specific bilingual templates available (e.g., French, German, Spanish, Italian).
• Growth Disorder Trials website text / digital ad templates — online recruitment content.
• HCP letters and HCP factsheets — outreach to healthcare professionals to identify eligible patients.
• Advocacy flyer and advocacy outreach text — materials intended for patient advocacy groups and caregivers.
• Print ads and brochures — traditional media recruitment materials.
• Patient letters and Patient material packets — direct mail/email to potential participants or families.
• Pre-ICF telephone data consent (Scout Clinical) — telephone-based pre-screening and consent procedures.

France

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

29-12-2025

Processing Time Days

340

Number Of Sites

5

Number Of Participants

10

Germany

Earliest CTIS Part Ii Submission Date

09-01-2025

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

371

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

24-01-2025

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

362

Number Of Sites

2

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

31-12-2024

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

415

Number Of Sites

6

Number Of Participants

10

Primary sponsor

Full Name

Biomarin Pharmaceutical Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Multiple clinical trial services including Medical imaging, In-home health, Site and contract negotiation, Patient recruitment materials, Language service (sponsorDuties entries)

Name

Medpace Belgium

Responsibilities

Clinical trial services (sponsorDuties code 4)

Third parties

• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties: code 15 (value: Patient reimbursment)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Medpace Belgium","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [1,12,15 (value: Medical imaging, In-home health, Site and contract negotiation, Patient recuritment materials, Language service),2,4,5,8]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties codes: [15] (value: sample storage)","organisation_type":"Pharmaceutical company"}