A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for
 the treatment of children with Achondroplasia.
This is a Phase 3 randomized, placebo-controlled, double-blind multicenter study with
 approximately 110 subjects, aged 5 to < 18 years old. Subjects with documented Achondroplasia
 confirmed by genetic testing will have been enrolled in Study 111-901 for at least a 6-month
 period immediately before entering into the 111-301 study. Eligible subjects will be randomly
 assigned to one of two treatment groups: placebo or BMN 111 at 15 μg/kg. The route of
 administration is subcutaneous injection and the frequency is daily.
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