Achondroplasia
Conditions
Keywords
ACH, Achondroplasia, Bone Diseases, Bone Diseases, Developmental, Dwarfism, Genetic Diseases, Inborn, Musculoskeletal Diseases, Natriuretic Agents, Natriuretic Peptide, C-Type, Osteochondrodysplasias, Physiological Effects of Drugs, Skeletal Dysplasias
Brief summary
The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for the treatment of children with Achondroplasia
Interventions
DRUGBMN 111
Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have completed Study 111-301 * Female \>= 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, willing to use a highly effective method of contraception while participating in the study * Are willing and able to perform all study procedures * 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. Also, subjects under the age of majority are willing and able to provide written assent (if required by local regulations or the IRB/IEC) after the nature of the study has been explained and prior to performance of any research-related procedure. Subjects who reach the age of majority in their country while the study is ongoing will be asked to provide their own written consent again upon reaching the legal age of majority.
Exclusion criteria
* Permanently discontinued BMN 111 or placebo prior to completion of the 111-301 study * Have a clinically significant finding or arrhythmia on Baseline ECG that indicates abnormal cardiac function * Evidence of decreased growth velocity (\<1.5 cm/year) as assessed over a period of at least 6 months or of growth plate closure (proximal tibia, distal femur) through bilateral lower extremity X-rays. * Require any investigational agent prior to completion of study period * Current therapy with medications known to alter renal function * Pregnant or breastfeeding or plan to become pregnant during study * Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason. * Have a condition or circumstance that, in the view of the investigator, places the subject at high risk for poor treatment compliance or for not completing the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baselines in mean annualized growth velocity | Through study completion, an average of 1 year | Long term efficacy as measured by change in annualized growth velocity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) | Through study completion, every 12 months | — |
| Characterize the elimination half-life of BMN 111 (t1⁄2) | Through study completion, every 12 months | — |
| Characterize the apparent clearance of drug | Through study completion, every 12 months | — |
| Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) | Through study completion, every 12 months | — |
| Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) | Through study completion, every 12 months | — |
| Characterize maximum concentration (Cmax) of BMN 111 in plasma | Through study completion, every 12 months | — |
| Changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire | Through study completion, every 6-12 months | — |
| Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire | Through study completion, every 12 months | — |
| BMN 111 Activity Biomarkers | Through study completion, every 12 months | BMN 111 activity will be assessed by measuring bone and collagen metabolism |
| Evaluate change from baseline in body proportion ratios of the extremities | Through study completion, every 6 months | — |
| Effect of BMN 111 on bone morphology and quality | Through study completion, every 12 months for DXA or 2 years for X-ray | The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via X-Ray and Dual X-ray Absorptiometry |
| Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) | Through study completion, every 12 months | — |
| Final Adult Height | Up to at least 16 years of age for females and 18 years of age for males | Height at 16 years for females and 18 years for males |
Countries
Australia, Germany, Japan, Spain, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed