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Trial record 1 of 1 for:    111-301
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A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

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ClinicalTrials.gov Identifier: NCT03197766
Recruitment Status : Completed
First Posted : June 23, 2017
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE May 23, 2017
First Posted Date  ICMJE June 23, 2017
Last Update Posted Date May 15, 2020
Actual Study Start Date  ICMJE December 12, 2016
Actual Primary Completion Date October 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2017)
Change from baseline in mean Annualized Growth Velocity [ Time Frame: one year ]
Evaluate change from baseline in mean annualized growth velocity at 52 weeks in subjects treated with BMN 111 compared with control subjects in the placebo group
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Change from baseline in height Z-scores [ Time Frame: one year ]
    Evaluate change from baseline in height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
  • Change from baseline in upper to lower segment body ratio [ Time Frame: one year ]
    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
  • Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: 54 weeks ]
    The number of subjects who reported at least one adverse event
  • Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: 52 weeks ]
  • Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: 52 weeks ]
  • Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: 52 weeks ]
  • Characterize the elimination half-life of BMN 111 (t½) [ Time Frame: 52 weeks ]
  • Characterize the apparent clearance of drug [ Time Frame: 52 weeks ]
  • Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: 52 weeks ]
  • Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: 52 weeks ]
  • Change from baseline in body proportion ratios of the extremities in subjects [ Time Frame: one year ]
  • Effect of BMN 111 on bone morphology and quality [ Time Frame: Screening, weeks 26 and 52 ]
    The effect of BMN 111 on bone morphology/quality will be assessed by X-ray and dual X-ray absorptiometry (DXA)
  • Potential changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire [ Time Frame: Screening, weeks 26 and 52 ]
  • Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [ Time Frame: Screening, weeks 26 and 52 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2017)
  • Change from baseline in height Z-scores [ Time Frame: one year ]
    Evaluate change from baseline in height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
  • Change from baseline in upper to lower segment body ratio [ Time Frame: one year ]
    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
  • Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: 54 weeks ]
    The number of subjects who reported at least one adverse event
  • Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: 52 weeks ]
  • Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: 52 weeks ]
  • Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: 52 weeks ]
  • Characterize the elimination half-life of BMN 111 (t½) [ Time Frame: 52 weeks ]
  • Characterize the apparent clearance of drug [ Time Frame: 52 weeks ]
  • Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: 52 weeks ]
  • Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: 52 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: May 29, 2019)
  • Optional exploratory genomic biomarker analysis [ Time Frame: Weeks 6 and 52 ]
    Exploratory genomic analysis of genes associated with CNP signaling
  • Optional sleep study scores by polysomnography in a subset of subjects [ Time Frame: Screening and week 52 ]
  • BMN 111 Activity biomarkers [ Time Frame: Day 1 and weeks 13, 26,39, 52, and 54 ]
    BMN 111 activity will be assessed by measuring bone and collagen metabolism
Original Other Pre-specified Outcome Measures
 (submitted: June 21, 2017)
  • Change from baseline in body proportion ratios of the extremities in subjects [ Time Frame: one year ]
  • Effect of BMN 111 on bone morphology and quality [ Time Frame: Screening, weeks 26 and 52 ]
    The effect of BMN 111 on bone morphology will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry
  • BMN 111 Activity biomarkers [ Time Frame: Day 1 and weeks 13, 26,39, 52, and 54 ]
    BMN 111 activity will be assessed by measuring bone and collagen metabolism
  • Optional exploratory genomic biomarker analysis [ Time Frame: Weeks 6 and 52 ]
    Exploratory genomic analysis of genes associated with CNP signaling
  • Optional sleep study scores by polysomnography in a subset of subjects [ Time Frame: Screening and week 52 ]
  • Potential changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire [ Time Frame: Screening, weeks 26 and 52 ]
  • Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [ Time Frame: Screening, weeks 26 and 52 ]
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
Official Title  ICMJE A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
Brief 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Achondroplasia
Intervention  ICMJE
  • Drug: BMN 111
    Subcutaneous injection of 15 μg/kg of BMN 111 daily
    Other Names:
    • Vosoritide
    • Modified recombinant human C-type natriuretic peptide
  • Drug: Placebo
    Subcutaneous injection of 15 μg/kg of placebo daily
Study Arms  ICMJE
  • Experimental: Active BMN 111
    Daily subcutaneous injection of 15 micrograms per kilogram BMN111
    Intervention: Drug: BMN 111
  • Placebo Comparator: Placebo
    Daily subcutaneous injection of placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 29, 2019)
121
Original Estimated Enrollment  ICMJE
 (submitted: June 21, 2017)
110
Actual Study Completion Date  ICMJE October 30, 2019
Actual Primary Completion Date October 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Germany,   Japan,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03197766
Other Study ID Numbers  ICMJE 111-301
2015-003836-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party BioMarin Pharmaceutical
Study Sponsor  ICMJE BioMarin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director, MD BioMarin Pharmaceutical
PRS Account BioMarin Pharmaceutical
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP