A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Vosoritide in Infants and Young Children with Hypochondroplasia, Aged 0 to < 36 Months

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biomarin Pharmaceutical Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Genetic Phenomena [G05]

Trial duration

22 Dec 2025 → ongoing

Decision date (initial)

2025-10-31

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioMarin Pharmaceutical Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenomic, Others, Pharmacokinetic, Efficacy, Pharmacodynamic

To evaluate the safety and tolerability of vosoritide versus placebo in children with HCH aged 0 to < 36 months
To evaluate the effect on linear growth of vosoritide versus placebo

Secondary objectives 9

1. To evaluate the effect of vosoritide versus placebo on height gain
2. To evaluate the effect of vosoritide versus placebo on growth
3. To evaluate the effect of vosoritide versus placebo on body proportions
4. To evaluate the effect of vosoritide versus placebo on arm span
5. To evaluate the effect of vosoritide versus placebo on bone quality by DXA
6. To evaluate the PK profile of vosoritide
7. To evaluate the effect of vosoritide versus placebo on PD biomarkers
8. To monitor the incidence of otitis media
9. To monitor the frequency of seizures

Conditions and MedDRA coding

Hypochondroplasia

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002033-PIP02-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Participants must be 0 to < 36 months of age at randomization.
2. 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).
3. 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.
4. 4. Participant’s weight at the Day 1 visit (pre-treatment) must be ≥ 3 kg.
5. 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.
6. 6. Parent(s) or caregiver(s) are willing to administer daily injections to the participants and willing to complete the required training.

Exclusion criteria 25

1. 1. Short stature condition other than HCH (eg, ACH, trisomy 21, pseudoachondroplasia).
2. 10. Have had regular long-term treatment (> 1 month) with oral corticosteroids in the 12 months prior to Screening.
3. 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.
4. 12. Have had a fracture of the long bones or spine within 6 months prior to Screening.
5. 13. Require any investigational agent prior to completion of study period.
6. 14. Have received another investigational product or investigational medical device within 30 days prior to the Screening visit.
7. 15. Have used any other investigational product or investigational medical device for the treatment of HCH or short stature at any time
8. 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).
9. 17. Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy.
10. 18. Have known hypersensitivity to vosoritide or its excipients.
11. 19. Have a history of hip surgery or severe hip dysplasia.
12. 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.
13. 20. Have a history of clinically significant hip injury in the 30 days prior to Screening.
14. 21. Have a history of slipped capital femoral epiphysis or avascular necrosis of the femoral head.
15. 22. Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant.
16. 23. Have a condition or circumstance that places the participant at high risk for poor treatment compliance or for not completing the study.
17. 24. Have any concurrent disease or condition that will interfere with study participation or safety evaluations, for any reason.
18. 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.
19. 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
20. 5. Have an unstable medical condition likely to require surgical intervention during the study period.
21. 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.
22. 7. Taking any of the prohibited medications.
23. 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.
24. 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.
25. Please see protocol for complete details.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. • Incidence of TEAEs versus placebo over the course of the study
2. • Incidence of SAEs versus placebo over the course of the study
3. • Changes in standard clinical laboratory values (urinalysis, chemistry, hematology) versus placebo over the course of the study
4. • Changes in vital signs versus placebo over the course of the study
5. • Change from baseline at Week 52 versus placebo in height Z-score

Secondary endpoints 12

1. Change (Chg) baseline (bl) – Week (W)52 vs placebo (plcb) in height
2. 6-month interval AGV at W52 vs plcb
3. Chg bl - W52 vs plcb in upper to lower body segment ratio
4. Chg bl - W52 vs plcb in arm span
5. Chg bl - W52 vs plcb in total body BMD Zscore by DXA
6. Chg bl - W52 vs plcb in lumbar spine BMD Zscore by DXA
7. Chg bl - W52 vs plcb in tot. body BMC by DXA
8. Chg bl - W52 vs plcb in lumbar spine BMC by DXA
9. PK
10. Chg from pre-dose vs plcb in cGMP
11. Incidence of otitis media vs plcb
12. Seizure freq. vs plcb

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biomarin Pharmaceutical Inc.

Sponsor organisation

Biomarin Pharmaceutical Inc.

Address

105 Digital Drive

City

Novato

Postcode

94949-8703

Country

United States

Scientific contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

BioMarin Pharmaceutical Inc.

Public contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

BioMarin Pharmaceutical Inc.

Third parties 17

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications