DRUG
BMN 111
Subcutaneous injection of 15 μg/kg of BMN 111 daily
Status
Completed
Phase
Phase 3
Enrollment
121
Locations
24
Results
Posted
Publications
4
Study 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.
Interventions
DRUG
Subcutaneous injection of 15 μg/kg of BMN 111 daily
DRUG
Subcutaneous injection of 15 μg/kg of placebo daily
Timeline
First posted
Jun 23, 2017
Study start
Dec 12, 2016
Primary completion
Oct 30, 2019
Study completion
Oct 30, 2019
Results posted
Mar 2, 2022
Registry updated
Mar 2, 2022
Outcomes
Change From Baseline in Annualized Growth Velocity (AGV) at Week 52
Time frame · At Baseline and Week 52
AGV at a Post-baseline Visit is defined as \[(Height at Post-baseline Visit - Height at Baseline)/(Date of Post-baseline Visit - Date of Baseline Assessment)\] x 365.25 AGV at Baseline is defined as \[(Height at Baseline - last height measurement in Study 111-901 at least 6 months prior to Baseline)/(Date of Baseline Assessment - Date of last height measurement in Study 111-901 at least 6 months prior to Baseline)\] x 365.25
Change From Baseline in Height Z-score at Week 52
Time frame · At baseline and Week 52
Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention. A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age. A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age. To conclude if the height Z score increases then this means the height deficit has decreased.
Change From Baseline in Upper to Lower Segment Body Ratio at Week 52
Time frame · At baseline and Week 52
Evaluate change from baseline in mean upper:lower segment body ratio in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment
Time frame · Up to Week 56
AEs with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. serious adverse event (SAE)
Eligibility
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
Study locations
Australia · Germany · Japan · Spain · Turkey (Türkiye) · United Kingdom · United States. Showing up to 24 locations stored in the fast local snapshot.
Children's Hospital & Research Center Oakland
Oakland, California, United States
Harbor - UCLA Medical Center
Torrance, California, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Emory University
Decatur, Georgia, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Johns Hopkins University
Baltimore, Maryland, United States
University of Missouri
Columbia, Missouri, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Baylor College of Medicine
Houston, Texas, United States
Seattle Children's Hospital
Seattle, Washington, United States
Medical College of Wisconsin, Children's Hospital
Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Murdoch Children's Research Institute
Parkville, Victoria, Australia
Otto-von-Guericke Universitaet, Universitaetskinderklinik
Magdeburg, Germany
Universitätsklinikum Münster
Münster, Germany
Osaka University Hospital
Osaka, Japan
Saitama Children's Medical Center
Saitama, Japan
Tokushima University Hospital
Tokushima, Japan
Institut Catala de Traumatologica I Medicina de l'Esport
Barcelona, Spain
Hospital Sant Joan de Deu
Barcelona, Spain
Hospital Universitario Virgen de la Victoria
Málaga, Spain
Acibadem University School of Medicine
Istanbul, Turkey (Türkiye)
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
London, United Kingdom
Sheffield Children's NHS Foundation Trust
Sheffield, United Kingdom
Publications
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