Achondroplasia
Conditions
Sponsors
BioMarin Pharmaceutical Inc.(ICCC:EPS International Holdings Co. Ltd.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria Individuals eligible to participate in this study must meet all of the following inclusion criteria: 1. 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 in their country are willing and able to provide written assent (if required by local regulations or the IRB/EC) 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 18 years while the study is ongoing will be asked to provide their own written consent. 2. 5 to < 18 years old at study entry 3. Have ACH, documented by clinical grounds and confirmed by genetic testing 4. Have at least a 6-month period of pretreatment growth assessments, including standing height, and are currently active participants in 111-901 5. Females over 10 years old or who have begun menses must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study 6. If sexually active, willing to use a highly effective method of contraception while participating in the study 7. Are ambulatory and able to stand without assistance 8. Are willing and able to perform all study procedures as physically possible 9. Caregivers are willing to administer daily injections to the subjects and complete the required training
Exclusion criteria
Exclusion criteria: -Hyochondroplasia or short stature condition other than ACH -Have any of the following: *Hypothyroidism or hyperthyroidism *Insulin-requiring diabetes mellitus *Autoimmune inflammatory disease *Inflammatory bowel disease *Autonomic neuropathy -History of any of the following: *Renal insufficiency defined as serum creatinine > 2 mg/dL *Chronic anemia *Baseline systolic blood pressure (BP) 450 msec -Have an unstable condition likely to require surgical intervention during the study (including progressive cervical medullary compression or severe untreated sleep apnea) -Decreased growth velocity (<1.5 cm/yr) over a period of 6 months or evidence of growth plate closure (proximal tibia, distal femur) -Treated with growth hormone, insulin-like growth factor 1(IGF-1), or anabolic steroids in the previous 6 months or treatment greater than 6 months at any time -Greater than 1 month treatment with oral corticosteroids (low-dose ongoing inhaled steroid for asthma, or intranasal steroids, are acceptable) in the previous 12 months -Planned or expected to have limb-lengthening surgery during the study period. Subjects with previous limb- lengthening surgery may enroll if surgery occurred at least 18 months prior to the study and healing is complete without sequelae. -Planned or expected bone-related surgery (ie. surgery involving disruption of bone cortex, excluding tooth extraction), during the study period. Subjects with previous bone-related surgery may enroll if surgery occurred at least 6 months prior to the study and healing is complete without sequelae. -Had a fracture of the long bones or spine within 6 months prior to screening -History of severe untreated sleep apnea -New initiation of sleep apnea treatment (e.g. CPAP or sleep apnea-mitigating surgery) in the previous 2 months prior to screening -History of hip surgery or hip dysplasia atypical for achondroplastic subjects -History of clinically significant hip injury in the 30 days prior to screening -History of slipped capital femoral epiphysis or avascular necrosis of the femoral head -Abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant -Concurrent disease or condition that would interfere with study participation or safety evaluations, for any reason -Condition or circumstance that places the subject at high risk for poor treatment compliance or for not completing the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Evaluate change from baseline in mean annualized growth velocity at 52 weeks in subjects treated with BMN 111 compared with control subjects in the placebo group | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy pharmacokinetics -Change from baseline in height Z-scores [ Time Frame: one year ] Evaluate change from baseline in height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks -Change from baseline in upper to lower segment body ratio [ Time Frame: one year ] Evaluate change from baseline in mean upper:lower segment body ratio in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks -Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: 54 weeks ] The number of subjects who reported at least one adverse event -Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: 52 weeks ] -Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC 0-infinity) [ Time Frame: 52 weeks ] -Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: 52 weeks ] -Characterize the elimination half-life of BMN 111 (t 1/2) [ Time Frame: 52 weeks ] -Characterize the apparent clearance of drug [ Time Frame: 52 weeks ] -Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: 52 weeks ] -Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: 52 weeks ] -Change from baseline in body proportion ratios of the extremities in subjects [ Time Frame: one year ] -Effect of BMN 111 on bone morphology and quality [ Time Frame: Screening, weeks 26 and 52 ] The effect of BMN 111 on bone morphology/quality will be assessed by X-ray and dual X-ray absorptiometry (DXA) -Potential changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire [ Time Frame: Screening, weeks 26 and 52 ] -Evaluate potential changes in functional independence as measured by the WeeFIM clinician-reported outcome[ Time Frame: Screening, week 26 and | — |
Countries
Europe, Japan, North America, Oceania
Outcome results
None listed