- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03197766
A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Westmead, New South Wales, Australia, 2145
- The Children's Hospital at Westmead
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Victoria
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Parkville, Victoria, Australia, 3052
- Murdoch Children's Research Institute
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Magdeburg, Germany, 39120
- Otto-von-Guericke Universitaet, Universitaetskinderklinik
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Münster, Germany, 48149
- Universitatsklinikum Munster
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Osaka, Japan
- Osaka University Hospital
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Saitama, Japan
- Saitama Children's Medical Center
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Tokushima, Japan
- Tokushima University Hospital
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Barcelona, Spain, 08950
- Hospital Sant Joan de Deu
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Barcelona, Spain, 08028
- Institut Catala de Traumatologica I Medicina de l'Esport
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Málaga, Spain, 29010
- Hospital Universitario Virgen de la Victoria
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Istanbul, Turkey, 34752
- Acibadem University School of Medicine
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London, United Kingdom, SE1 9RT
- Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
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Sheffield, United Kingdom, S10 2TH
- Sheffield Children's NHS Foundation Trust
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California
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Oakland, California, United States, 94609
- Children's Hospital & Research Center Oakland
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Torrance, California, United States, 90509
- Harbor - UCLA Medical Center
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Delaware
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Wilmington, Delaware, United States, 19803
- Alfred I. DuPont Hospital for Children
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Georgia
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Decatur, Georgia, United States, 30033
- Emory University
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Illinois
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Chicago, Illinois, United States, 60611
- Ann and Robert H. Lurie Children's Hospital of Chicago
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Missouri
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Columbia, Missouri, United States, 65201
- University of Missouri
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Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Medical College of Wisconsin, Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Daily subcutaneous injection of placebo
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Subcutaneous injection of 15 μg/kg of placebo daily
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Experimental: Active BMN 111
Daily subcutaneous injection of 15 micrograms per kilogram BMN111
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Subcutaneous injection of 15 μg/kg of BMN 111 daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Annualized Growth Velocity (AGV) at Week 52
Time Frame: At Baseline and Week 52
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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 |
At Baseline and Week 52
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Height Z-score at Week 52
Time Frame: At baseline and Week 52
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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. |
At baseline and Week 52
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Change From Baseline in Upper to Lower Segment Body Ratio at Week 52
Time Frame: At baseline and Week 52
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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
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At baseline and Week 52
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Summary of Subjects Experiencing Adverse Events (AEs) During Treatment
Time Frame: Up to Week 56
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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) |
Up to Week 56
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 111-301
- 2015-003836-11 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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PfizerTerminatedAchondroplasiaUnited States, Australia, Belgium, Denmark, Italy, Portugal, Spain
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BioMarin PharmaceuticalActive, not recruitingAchondroplasiaUnited States, Australia, Japan, United Kingdom
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BioMarin PharmaceuticalPicnicHealthRecruitingAchondroplasiaUnited States
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Clinical Trials on BMN 111
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Andrew DauberActive, not recruiting
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BioMarin PharmaceuticalActive, not recruitingAchondroplasiaUnited States, Australia, Japan, United Kingdom
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BioMarin PharmaceuticalCompletedAchondroplasiaUnited States
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BioMarin PharmaceuticalTerminatedAchondroplasiaUnited States
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BioMarin PharmaceuticalActive, not recruitingAchondroplasiaUnited States, Australia, Germany, Spain, United Kingdom, Japan, Turkey
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BioMarin PharmaceuticalActive, not recruitingAchondroplasiaUnited States, Australia, France, United Kingdom
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BioMarin PharmaceuticalCompletedAchondroplasiaUnited States, Australia, United Kingdom, Japan
-
BioMarin PharmaceuticalCompletedAchondroplasiaUnited States, Australia, France, United Kingdom
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BioMarin PharmaceuticalRecruitingHereditary Angioedema | HAEUnited States, Spain, Australia
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BioMarin PharmaceuticalCompletedPompe DiseaseUnited States, United Kingdom, France, Australia, Germany