A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

This is an interventional treatment trial for Achondroplasia focused on measuring Achondroplasia, Dwarfism, Bone Diseases, Bone Diseases, Developmental, ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases, Natriuretic Agents, Physiological Effects of Drugs, Skeletal Dysplasias, Genetic Diseases, Inborn, Osteochondrodysplasias Read More

Inclusion Criteria

• Parent(s) or guardian(s) consent
• 5 to < 18 years old
• ACH, documented and confirmed by genetic testing
• At least a 6-month period of pretreatment growth assessment in Study 111-901 before study entry
• If sexually active, willing to use a highly effective method of contraception
• Ambulatory and able to stand without assistance

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

• History of any of the following:

  • Renal insufficiency defined as serum creatinine > 2 mg/dL
  • Chronic anemia
  • Baseline systolic blood pressure (BP) < 70 millimeters of mercury (mm Hg) or recurrent symptomatic hypotension (defined as episodes of low BP generally accompanied by symptoms ie, dizziness, fainting) or recurrent symptomatic orthostatic hypotension

  • Cardiac or vascular disease

    • Have a clinically significant finding or arrhythmia on screening electrocardiogram (ECG) that indicates abnormal cardiac function or conduction or Fridericias corrected QTc-F > 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