VOSORITIDE for Hypochondroplasia

Inclusion criteria

• {"criterion_text":"- 1. Participants must be 0 to < 36 months of age at randomization.\n- 2. Participants must have a confirmed genetic diagnosis of HCH (obtained via whole genome sequencing; presence of a FGFR3 pathogenic variant associated with HCH). Genetic confirmation of disease can be obtained either in Study 111-902 or during the Screening period of 111-212 (Appendix 4).\n- 3. Participants aged 0 to < 12 months must have a height Z-score of ≤ −1.0 SDS and participants aged ≥ 12 to < 36 months must have a height Z-score of ≤ −2.0 SDS in reference to the average stature of the same sex and age, as calculated using the Center for Disease Control and Prevention (CDC) growth charts (https://www.cdc.gov/growthcharts/zscore.htm) as assessed at Screening.\n- 4. Participant’s weight at the Day 1 visit (pre-treatment) must be ≥ 3 kg.\n- 5. Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure.\n- 6. Parent(s) or caregiver(s) are willing to administer daily injections to the participants and willing to complete the required training."}

Exclusion criteria

• {"criterion_text":"- 1. Short stature condition other than HCH (eg, ACH, trisomy 21, pseudoachondroplasia).\n- 18. Have known hypersensitivity to vosoritide or its excipients.\n- 19. Have a history of hip surgery or severe hip dysplasia.\n- 2. Have any of the following: • Hypothyroidism or hyperthyroidism, growth hormone deficiency, hypercortisolism or hypopituitarism, or other endocrine cause of short stature. • Insulin-requiring diabetes mellitus. • Autoimmune inflammatory disease (e.g., systemic lupus erythematosus, juvenile dermatomyositis, scleroderma). • Other chronic diseases that per investigator determination may be causative of a participant’s short stature, including conditions causing malnutrition (e.g., inflammatory bowel disease, cystic fibrosis, celiac disease, eating disorders). • Autonomic neuropathy.\n- 20. Have a history of clinically significant hip injury in the 30 days prior to Screening.\n- 21. Have a history of slipped capital femoral epiphysis or avascular necrosis of the femoral head.\n- 22. Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant.\n- 23. Have a condition or circumstance that places the participant at high risk for poor treatment compliance or for not completing the study.\n- 24. Have any concurrent disease or condition that will interfere with study participation or safety evaluations, for any reason.\n- 3. Have a history of any of the following: • Renal insufficiency defined as estimated glomerular filtration rate (eGFR) of < 60 ml/min/1.73 m2 using the revised Schwartz Pediatric Bedside eGFR formula. • Chronic anemia or hemoglobin (Hgb) < 10.0 g/dL (Screening lab test). • Recurrent symptomatic hypotension (i.e., dizziness, fainting, postural tachycardia) or recurrent symptomatic orthostatic hypotension.\n- 4. History of cardiac or vascular disease, including the following: • Cardiac dysfunction • Hypertrophic cardiomyopathy • Pulmonary hypertension • Congenital heart disease with ongoing cardiac dysfunction • Cerebrovascular disease • Aortic insufficiency or other clinically significant valvular dysfunction • Clinically significant atrial or ventricular arrhythmia\n- 10. Have had regular long-term treatment (> 1 month) with oral corticosteroids in the 12 months prior to Screening.\n- 5. Have an unstable medical condition likely to require surgical intervention during the study period.\n- 6. Have documented uncorrected vitamin D deficiency: 25-hydroxy-vitamin D ≤ 15 ng/mL (37.5 nmol/L). Note: participants with deficiency may receive supplementation and re-screen after 8 weeks.\n- 7. Taking any of the prohibited medications.\n- 8. Require current chronic therapy with antihypertensive medication or any medication that may compromise the safety or ability of the participant to participate in this clinical study.\n- 9. Have been treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time.\n- Please see protocol for complete details.\n- 11. Have condition(s) requiring a daily inhaled steroid dose > 400 µg of inhaled budesonide per day or equivalent. Low-dose ongoing inhaled steroids for asthma, or intranasal steroids, are acceptable.\n- 12. Have had a fracture of the long bones or spine within 6 months prior to Screening.\n- 13. Require any investigational agent prior to completion of study period.\n- 14. Have received another investigational product or investigational medical device within 30 days prior to the Screening visit.\n- 15. Have used any other investigational product or investigational medical device for the treatment of HCH or short stature at any time\n- 16. Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN or total bilirubin ≥ 1.5 × ULN at screening (except for participants with a known history of Gilberts).\n- 17. Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy."}

Primary endpoints

• {"endpoint_text":"- • Incidence of TEAEs versus placebo over the course of the study","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events recorded during the study and compared versus placebo over the study duration."}
• {"endpoint_text":"- • Incidence of SAEs versus placebo over the course of the study","definition_or_measurement_approach":"Incidence of serious adverse events recorded during the study and compared versus placebo over the study duration."}
• {"endpoint_text":"- • Changes in standard clinical laboratory values (urinalysis, chemistry, hematology) versus placebo over the course of the study","definition_or_measurement_approach":"Change from baseline in standard clinical laboratory parameters (urinalysis, clinical chemistry, hematology) versus placebo as assessed during scheduled study visits."}
• {"endpoint_text":"- • Changes in vital signs versus placebo over the course of the study","definition_or_measurement_approach":"Change from baseline in vital signs versus placebo as measured at study visits."}
• {"endpoint_text":"- • Change from baseline at Week 52 versus placebo in height Z-score","definition_or_measurement_approach":"Change from baseline in height Z-score at Week 52 versus placebo; Z-score calculated using CDC growth charts as referenced in eligibility criteria."}

Secondary endpoints

• {"endpoint_text":"- Change (Chg) baseline (bl) – Week (W)52 vs placebo (plcb) in height","definition_or_measurement_approach":"Change from baseline to Week 52 in absolute height versus placebo."}
• {"endpoint_text":"- 6-month interval AGV at W52 vs plcb","definition_or_measurement_approach":"Annualized growth velocity (AGV) measured at 6-month intervals, compared at Week 52 versus placebo."}
• {"endpoint_text":"- Chg bl - W52 vs plcb in upper to lower body segment ratio","definition_or_measurement_approach":"Change from baseline to Week 52 in upper-to-lower body segment ratio versus placebo."}
• {"endpoint_text":"- Chg bl - W52 vs plcb in arm span","definition_or_measurement_approach":"Change from baseline to Week 52 in arm span versus placebo."}
• {"endpoint_text":"- Chg bl - W52 vs plcb in total body BMD Zscore by DXA","definition_or_measurement_approach":"Change from baseline to Week 52 in total body bone mineral density (BMD) Z-score measured by DXA versus placebo."}
• {"endpoint_text":"- Chg bl - W52 vs plcb in lumbar spine BMD Zscore by DXA","definition_or_measurement_approach":"Change from baseline to Week 52 in lumbar spine BMD Z-score measured by DXA versus placebo."}
• {"endpoint_text":"- Chg bl - W52 vs plcb in tot. body BMC by DXA","definition_or_measurement_approach":"Change from baseline to Week 52 in total body bone mineral content (BMC) measured by DXA versus placebo."}
• {"endpoint_text":"- Chg bl - W52 vs plcb in lumbar spine BMC by DXA","definition_or_measurement_approach":"Change from baseline to Week 52 in lumbar spine BMC measured by DXA versus placebo."}
• {"endpoint_text":"- PK","definition_or_measurement_approach":"Pharmacokinetic analyses of vosoritide (PK) as defined in the study's PK sampling and analysis plan."}
• {"endpoint_text":"- Chg from pre-dose vs plcb in cGMP","definition_or_measurement_approach":"Change from pre-dose in cGMP (cyclic guanosine monophosphate) versus placebo."}
• {"endpoint_text":"- Incidence of otitis media vs plcb","definition_or_measurement_approach":"Incidence of otitis media events recorded during the study compared to placebo."}
• {"endpoint_text":"- Seizure freq. vs plcb","definition_or_measurement_approach":"Frequency of seizures recorded during the study compared to placebo."}

Methods

• Digital advertisements (web ad banners, digital ad templates) targeting parents/caregivers (documents: K2_*_Recruiment Material_Web_Ad_Banner) with country-specific versions for Germany, France, Italy.
• Website content (Growth Disorder Trials web text) in multiple languages to inform and recruit families (documents: K2_*_Recruitment Material_Growth Disorder Trials Website).
• Advocacy flyers and patient brochure distribution (documents: K2_*_Recruitment Material_Advocacy Flyer, Patient Brochure) targeted to patient/parent communities and advocacy channels (country versions present).
• Clinical trial material packets distributed to sites and families (documents: K2_*_Clinical Trial Material Packet).
• Site-level recruitment procedures (K1_*_Recruitment Procedure) used by investigators and sites.

France

Earliest CTIS Part Ii Submission Date

23-10-2025

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

8

Number Of Sites

2

Number Of Participants

10

Germany

Earliest CTIS Part Ii Submission Date

01-10-2025

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

110

Number Of Sites

3

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

04-08-2025

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

212

Number Of Sites

2

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

Medpace Belgium

Responsibilities

code 4

Name

Icon Clinical Research Limited

Responsibilities

codes 1,12,2,5

Name

Imperial Clinical Research Services International Ltd.

Responsibilities

Printing

Name

Longboat Clinical Limited

Responsibilities

Site training portal

Name

Clinilabs LLC

Responsibilities

sleep study analysis

Name

Suvoda LLC

Responsibilities

code 3

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Hpg LLC","duties_or_roles":"Subject recruitment support","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Medpace Belgium","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Longboat Clinical Limited","duties_or_roles":"Site training portal","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Clinilabs LLC","duties_or_roles":"sleep study analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Imperial Clinical Research Services International Ltd.","duties_or_roles":"Printing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Trulab Inc.","duties_or_roles":"Sample tracking technology","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Accellacare Limited","duties_or_roles":"Home nursing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"sample storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"Equipment rental","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Ncs Pearson Inc.","duties_or_roles":"Cognitive Development Assessment","organisation_type":"Pharmaceutical company"}