Hypochondroplasia
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of daily administration of vosoritide in participants with HCH aged 0 to \< 36 months over a 52-week period.
Detailed description
Study 111-212 is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of vosoritide versus placebo in infants and young children with HCH. Eligible participants with documented HCH confirmed by genetic testing will be randomized in a 1:1 ratio to receive vosoritide or placebo. Participants will receive study treatment daily for 52 weeks by subcutaneous (SC) injection, followed by a 2-week safety follow-up visit. Vosoritide dosing will follow a weight-band regimen.
Interventions
DRUGVosoritide
The vosoritide dose administered will be based on the participant's weight and will follow the weight-band dosing regimen approved for ACH
DRUGPlacebo
Subcutaneous injection of recommended dose of placebo
Sponsors
BioMarin Pharmaceutical
ICON Clinical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Months to 36 Months
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants must be 0 to \< 36 months of age at randomization. 2. Participants must have a confirmed genetic diagnosis of HCH (obtained via whole genome sequencing; presence of a FGFR3 pathogenic variant associated with HCH). 3. Participants aged 0 to \< 12 months must have a height Z-score of ≤ -1.0 SDS andparticipants 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. 4. Participant's weight at the Day 1 visit (pre-treatment) must be ≥ 3 kg. Key
Exclusion criteria
1. Short stature condition other than HCH (eg, ACH, trisomy 21, pseudoachondroplasia). 2. Have an unstable medical condition likely to require surgical intervention during the study period. 3. Taking any of the prohibited medications. 4. 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. 5. Require any investigational agent prior to completion of study period. 6. Have received another investigational product or investigational medical device within 30 days prior to the Screening visit. 7. Have used any other investigational product or investigational medical device for the treatment of HCH or short stature at any time. 8. Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy. 9. Have known hypersensitivity to vosoritide or its excipients. 10. Have a condition or circumstance that, in the view of the investigator, places the participant at high risk for poor treatment compliance or for not completing the study. 11. Have any concurrent disease or condition that, in the view of the investigator, will interfere with study participation or safety evaluations, for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | From baseline to end of treatment at 52 weeks | — |
| Incidence of serious adverse events versus placebo over the course of the study | From baseline to end of treatment at 52 weeks | — |
| Changes from baseline in standard clinical laboratory values (hematology, urinalysis, and chemistry) | At week 26, at week 52 | — |
| Changes from baseline in heart rate | At week 13, at week 26, at week 39, at week 52 | Units of measure: bpm |
| Change from baseline in height Z-score | At week 52 | — |
| Changes from baseline in respiratory rate | At week 13, at week 26, at week 39, at week 52 | Units of measure: breaths/min |
| Changes from baseline in temperature | At week 13, at week 26, at week 39, at week 52 | Units of measure: celsius |
| Changes from baseline in blood pressure | At week 13, at week 26, at week 39, at week 52 | Units of measure: mmHg |
Secondary
| Measure | Time frame |
|---|---|
| Change in height | At week 52 |
| Cumulative annualized growth velocity (AGV) | At week 52 |
| 6-month interval AGV | At week 26, at week 52 |
| Change from baseline in upper to lower body segment ratio | At week 52 |
| Change from baseline in arm span | At week 52 |
| Change from baseline in total body (less head) bone mineral density (BMD) Z-score | At week 52 |
| Change from baseline in lumbar spine BMD Z-score | At week 52 |
| Change from baseline in total body (less head) bone mineral content (BMC) as measured by DXA | At week 52 |
| Change from baseline in lumbar spine BMC as measured by DXA | At week 52 |
| Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞) | At week 26, at week 52 |
| Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t) | At week 26, at week 52 |
| Elimination half-life of vosoritide (t½) | At week 26, at week 52 |
| Apparent clearance of vosoritide | At week 26, at week 52 |
| Apparent volume of distribution of vosoritide based upon the terminal phase (Vz/F) | At week 26, at week 52 |
| Time vosoritide is present at maximum concentration (Tmax) | At week 26, at week 52 |
| Maximum concentration (Cmax) of vosoritide in plasma | At week 26, at week 52 |
| Change from pre-dose at pre-specified timepoints versus placebo in cyclic guanine monophosphate (cGMP) | At week 26 and week 52 |
| Incidence of otitis media | From baseline to end of treatment at 52 weeks |
| Seizure frequency over the course of the study | From baseline to end of treatment at 52 weeks |
Countries
Australia, France, Germany, Italy, Japan, United Kingdom, United States
Contacts
CONTACTTrial Specialist
Outcome results
None listed