A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
Condition: Achondroplasia
MeSH terms: Achondroplasia
Intervention: BMN 111; Placebo
Intervention description: Subcutaneous injection of 15 μg/kg of BMN 111 daily; Subcutaneous injection of 15 μg/kg of placebo daily
Intervention MeSH terms: Natriuretic Peptide, C-Type
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 121.0
Sex: All
Minimum age: 5 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: 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

Summary:

      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.
    

Eligibility criteria:

        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