Hypochondroplasia
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety and efficacy of daily doses of vosoritide in participants with HCH
Interventions
DRUGVosoritide
Open-label administration of vosoritide using weight-band dosing
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Participants must have completed the Week 52 visit for 111-303 or 111-212 and have open epiphyses as assessed by left hand antero-posterior (AP) X-rays * Parent(s) or guardian(s) must be willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any study-related procedure * Females ≥ 10 years old or who have begun menses must have a negative pregnancy test at the Baseline visit and be willing to have additional pregnancy tests during the study * If sexually active, participants must be willing to use a highly effective method of contraception while participating in the study * Participants are willing and able to perform all study procedures as physically possible * Parent(s) or caregiver(s) are willing to administer daily injections to the participants and willing to complete the required training
Exclusion criteria
* Permanently discontinued study treatment in the studies 111-303 or 111-212 * 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 as per standard of care * Taking or planning to take any prohibited medications * Planned or expected to have limb-lengthening surgery during the study period * Planned or expected bone-related surgery during the study period * Require any investigational agent prior to completion of study period * Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy * Have known hypersensitivity to vosoritide or its excipients * Is pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study * Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the long-term efficacy of vosoritide treatment until final adult height (FAH) | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | As measured by change from baseline in height Z-score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate long-term changes in Health-Related Quality of Life (HRQoL) | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | Change from baseline as measured by Quality of Life In Short-Statured Youth (QoLISSY) total score |
| Evaluate long-term effect of vosoritide treatment on bone quality | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | Change from baseline in bone mineral density (BMD) as measured by Dual X-Ray Absorptiometry |
| Evaluate long-term effect of vosoritide treatment on pubertal growth as measured by Tanner Staging | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | — |
| To monitor the incidence of otitis media | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | — |
| To monitor the frequency of seizures | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | — |
| Evaluate the maintenance effect of vosoritide treatment on standing height | Baseline to week 52 | change from baseline in height at Week 52 |
| Evaluate the maintenance effect of vosoritide treatment on standing height Z-score | Baseline to week 52 | Change from baseline in height Z-score at Week 52 |
| Evaluate long-term effect of vosoritide treatment on growth velocity | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | Absolute 6- or 12-month interval AGV |
| Evaluate long-term effect of vosoritide treatment on body proportionality | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | Change from baseline in upper to lower body segment ratio |
| Evaluate long-term effect of vosoritide treatment on bone metabolism biomarkers | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | Change from baseline in serum collagen X marker |
| Evaluate long-term effect of vosoritide treatment on bone age versus chronological age | Annually from enrollment through Final Adult Height, defined as 16 years of age for females and 18 years of age for males | As measured by left-hand and wrist x-ray |
Countries
Australia, Canada, France, Germany, Italy, Japan, Spain, United Kingdom, United States
Outcome results
None listed