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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active BMN 111 | Experimental | Once daily subcutaneous injections of recommended dose of BMN 111 based on weight-band dosing. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active BMN 111: Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily. | Drug | Modified recombinant human C-type natriuretic peptide (subject to adjustment per protocol) |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Number of study participants with treatment-emergent adverse events or serious adverse events | "Through study completion, an average of 5 years" |
| Evaluate change in height/length z-score in children with ACH treated with BMN 111 | "Through study completion, an average of 5 years" |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the change from baseline of mean annualized growth velocity (AGV) | "Through study completion, an average of 5 years" | |
| Characterize maximum concentration (Cmax) of BMN 111 in plasma | "Through study completion, an average of 5 years" |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director MD | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital & Research Center Oakland | Oakland | California | 94609 | United States | ||
| Harbor - UCLA Medical Center |
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| Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) | "Through study completion, an average of 5 years" |
| Characterize the elimination half-life of BMN 111 (t½) | "Through study completion, an average of 5 years" |
| Characterize the apparent clearance of drug | "Through study completion, an average of 5 years" |
| Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) | "Through study completion, an average of 5 years" |
| Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) | "Through study completion, an average of 5 years" |
| Evaluate the change from baseline on body proportion ratios of the extremities | "Through study completion, an average of 5 years" |
| Effect of BMN 111 on bone morphology and quality by XRay | "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 | "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]). | "Through study completion, an average of 5 years" |
| BMN 111 activity will be assessed by measuring bone and collagen metabolism | "Through study completion, an average of 5 years" |
| Describe the incidence of surgical and medical interventions related to achondroplasia | "Through study completion, an average of 5 years" |
| Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old. | "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. | "Through study completion, an average of 1 year" |
| Torrance |
| California |
| 90509 |
| United States |
| Alfred I. duPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| Emory University | Decatur | Georgia | 30033 | United States |
| Ann Robert and H. Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Cincinnati Childrens Hospital | Cincinnati | Ohio | 45229 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232-2578 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Medical College of Wisconsin, Children's Hospital | Milwaukee | Wisconsin | 53226 | United States |
| The Children's Hospital at Westmead | Westmead | New South Wales | 2145 | Australia |
| Murdoch Children's Research Institute | Parkville | Victoria | 3052 | Australia |
| Osaka University | Osaka | 565-0871 | Japan |
| Saitama Children's Medical Center | Saitama | 330-8777 | Japan |
| Tokushima University Hospital | Tokushima | 77-8503 | Japan |
| Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital | London | SE19RT | United Kingdom |
| Sheffield Children's NHS Foundation Trust | Sheffield | S102TH | United Kingdom |
| ID | Term |
|---|---|
| D000130 | Achondroplasia |
| D004392 | Dwarfism |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| ID | Term |
|---|---|
| D001848 | Bone Diseases, Developmental |
| D010009 | Osteochondrodysplasias |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C000632572 | vosoritide |
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