A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia

Inclusion Criteria: * Parent(s) or guardian(s) are willing and able to provide written, signed informed consent * 5 to 14 years old at end of study * ACH, documented by clinical grounds, confirmed by genetic testing * At least 6-month of pretreatment growth assessment in Study 111-901 before study entry, and one standing height at least 6 months prior to screening for 111-202 * Negative pregnancy test at the Screening Visit for females ≥ 10 years old or who have begun menses * If sexually active, willing to use a highly effective method of contraception while participating in the study * Ambulatory, able to stand without assistance * Willing and able to perform all study procedures as physically possible * Parents/caregivers willing to administer daily injections to the subjects Additional inclusion Criteria Optional, Open-label Extension Phase: * Appropriate written informed consent Exclusion Criteria: * Hypochondroplasia 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 * Recent acute illness associated with volume dehydration not completely resolved prior to the first dose of study drug * Unstable condition requiring surgical intervention during the study * Growth plates have fused * Have a history of any of the following: * Renal insufficiency, defined as creatinine \> 2 mg/dl * Anemia * Baseline systolic BP \< 75 mm Hg or recurrent symptomatic hypotension or recurrent symptomatic hypotension, recurrent symptomatic orthostatic hypotension * Cardiac or vascular disease, including the following: * Cardiac dysfunction (abnormal echocardiogram \[ECHO\] including left ventricle \[LV\] mass) at Screening Visit * Hypertrophic cardiomyopathy * Pulmonary Hypertension * Congenital heart disease with ongoing cardiac dysfunction * Cerebrovascular disease * Aortic insufficiency * Clinically significant atrial or ventricular arrhythmias * Have an ECG showing any of the following: * Right or left atrial enlargement or ventricular hypertrophy * PR (period of time from the beginning of atrial depolarization until the beginning of ventricular depolarization) interval \> 200 msec * QRS (The Q, R, and S heart waves that are measured on an electrocardiogram) interval \> 110 msec * Corrected QTc-F (Measure of the corrected time between the start of the Q wave and end of the T wave in the heart's electrical cycle) \> 450 msec * Second- or third-degree atrioventricular block * Documented Vitamin D deficiency * Require any investigational agent prior to completion of study period * Have received another investigational product or investigational medical device within 30 days before the Screening visit * Use of any other investigational product or investigational medical device for the treatment of ACH or short stature * Current chronic therapy with antihypertensive medications, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function * Treatment with growth hormone, IGF-1 (Insulin-like growth factor), or anabolic steroids in the previous 6 months or long-term treatment (\> 3 months) at any time * Long-term treatment (\> 1 month) with oral corticosteroids * Concomitant medication that prolongs the QT/QTc-F interval within 14 days or 5 half-lives, whichever is longer, before the Screening visit * Pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study * Limb-lengthening or bone-related surgery \< 18 months prior to study enrollment * Had a fracture of the long bones or spine within 6 months prior to screening (except for fracture of digits or toes) * AST (Aspartate Transaminase) or ALT (Alanine Transaminase) at least 3x upper limit of normal (ULN) or total bilirubin at least 2x ULN * Evidence of severe sleep apnea requiring surgery or new initiation of CPAP (Continuous positive airway pressure). * History of malignancy and chemotherapy/radiation or currently under work-up for suspected malignancy * Known hypersensitivity to BMN 111 or its excipients * 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 * Concurrent disease or condition that would interfere with study participation or safety * Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant as determined by the PI. * Have a history of hip surgery or severe hip dysplasia * Have a 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. * Are unable to lie flat when in prone position Additional Exclusion Criteria for Optional, Open-label Extension Phase: * Use of restricted therapies during the initial 6 months of the study * Permanently discontinued BMN 111 during the initial 6 months of the study