This is a Phase 2, open-label multi-center long-term extension study, with approximately 70 subjects, to evaluate the safety and efficacy of BMN111 in children with Achondroplasia until subjects reach near-adult final height. Eligible subjects will have completed 1 year of BMN111 or placebo treatment in the 111-206 study and once enrolled in the 111-208 extension study will receive a daily dose of BMN111 by subcutaneous injection according to their age as determined by 111-206.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
73
Modified recombinant human C-type natriuretic peptide (subject to adjustment per protocol)
Children's Hospital & Research Center Oakland
Oakland, California, United States
Harbor - UCLA Medical Center
Torrance, California, United States
Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of study participants with treatment-emergent adverse events or serious adverse events
Time frame: "Through study completion, an average of 5 years"
Evaluate change in height/length z-score in children with ACH treated with BMN 111
Time frame: "Through study completion, an average of 5 years"
Evaluate the change from baseline of mean annualized growth velocity (AGV)
Time frame: "Through study completion, an average of 5 years"
Characterize maximum concentration (Cmax) of BMN 111 in plasma
Time frame: "Through study completion, an average of 5 years"
Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)
Time frame: "Through study completion, an average of 5 years"
Characterize the elimination half-life of BMN 111 (t½)
Time frame: "Through study completion, an average of 5 years"
Characterize the apparent clearance of drug
Time frame: "Through study completion, an average of 5 years"
Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
Time frame: "Through study completion, an average of 5 years"
Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
Time frame: "Through study completion, an average of 5 years"
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Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Emory University
Decatur, Georgia, United States
Ann Robert and H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Cincinnati Childrens Hospital
Cincinnati, Ohio, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
Medical College of Wisconsin, Children's Hospital
Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
...and 6 more locations
Evaluate the change from baseline on body proportion ratios of the extremities
Time frame: "Through study completion, an average of 5 years"
Effect of BMN 111 on bone morphology and quality by XRay
Time frame: "Through study completion, an average of 5 years"
The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry
Time frame: "Through study completion, an average of 5 years"
Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth
Evaluate the long-term effect of BMN 111 on health-related quality of life, developmental status and functional independence, using age-specific QoL and functional independence questionnaires (Bayley-III, WeeFIM, ITQOL, QoLISSY, PedsQL, Child Behavior Checklist 1.5-5 \[CBCL 1.5-5\], Child Behavior Checklist 6-18 \[CBCL 6-18\]).
Time frame: "Through study completion, an average of 5 years"
BMN 111 activity will be assessed by measuring bone and collagen metabolism
Time frame: "Through study completion, an average of 5 years"
Describe the incidence of surgical and medical interventions related to achondroplasia
Time frame: "Through study completion, an average of 5 years"
Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old.
Time frame: "Through study completion, an average of 1 year"
Evaluate the effect of BMN 111 on skull and brain morphology, including foramen magnum, ventricular and brain parenchymal dimensions by MRI in patients up to 3 years old.
Time frame: "Through study completion, an average of 1 year"