a study to evaluate the efficacy and safety of bmn 111 in children with achondroplasia

Conditions: Achondroplasia

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.

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.

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

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