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A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia

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ClinicalTrials.gov Identifier: NCT03583697
Recruitment Status : Enrolling by invitation
First Posted : July 11, 2018
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE June 14, 2018
First Posted Date  ICMJE July 11, 2018
Last Update Posted Date May 24, 2019
Actual Study Start Date  ICMJE May 23, 2018
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
Evaluate the effect of BMN 111 on change from baseline in length/height Z-scores [ Time Frame: One year ]
Evaluate change from baseline in length/height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03583697 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: One year ]
  • Evaluate the effect of BMN 111 on change from baseline in AGV [ Time Frame: One year ]
  • Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA) [ Time Frame: One year ]
  • Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: One year ]
  • Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: One year ]
  • 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 ]
  • Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth [ Time Frame: One year ]
  • BMN 111 activity will be assessed by measuring bone and collagen metabolism [ Time Frame: One year ]
  • Evaluate the effect of BMN 111 on growth parameters and body proportions, including change from baseline in upper:lower segment body ratio [ Time Frame: One year ]
  • Evaluate the effect of BMN 111 on Sleep study scores by polysomnography [ Time Frame: One year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: One year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia
Official Title  ICMJE A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia, Age 0 to < 60 Months
Brief Summary Study 111-206 is a Phase 2 randomized, double-blind, placebo-controlled clinical trial of BMN 111 in infants and young children with a diagnosis of Achondroplasia.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Achondroplasia
Intervention  ICMJE
  • Drug: BMN 111
    Subcutaneous injection of 15 μg/kg of BMN 111 daily, Subject to adjustment per protocol
    Other Names:
    • Vosoritide
    • Modified recombinant human C-type natriuretic peptide
  • Drug: Placebo
    Subcutaneous injection of 15 μg/kg of placebo daily, Subject to adjustment per protocol
Study Arms  ICMJE
  • Experimental: Active BMN111
    Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily
    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 Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: July 10, 2018)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of ACH, confirmed by genetic testing
  • Age 0 to < 60 months at study entry (Day 1)
  • At least 6-month period of pretreatment growth assessment in Study 111-901 immediately before study entry (cohort 1 & 2) or at least 3 months of observation prior to treatment (cohort 3)

Exclusion Criteria:

  1. Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.)
  2. Have any of the following:

    • Hypothyroidism or hyperthyroidism
    • Insulin-requiring diabetes mellitus
    • Autoimmune inflammatory disease (including celiac disease, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma, etc.)
    • Inflammatory bowel disease
    • Autonomic neuropathy
  3. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F > 450 msec on screening ECG
  4. Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator and informed by the following assessments:

    • Physical exam (eg, neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins)
    • Polysomnography (eg, severe central sleep apnea)
    • MRI indicating presence of severe CMC or spinal cord damage
  5. Subject weight < 5.0 kg (cohort 1 & 2) or < 4.0 kg (cohort 3)
  6. Treatment with growth hormone within 6-months prior to screening or prolonged treatment (> 3 months) at any time
  7. Any history of spine or long-bone surgery or any bone-related surgery with chronic complications
  8. Any history of limb-lengthening surgery or planned limb-lengthening during the study
  9. Fracture of the long bones within 6 months prior to screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 59 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03583697
Other Study ID Numbers  ICMJE 111-206
2016-003826-18 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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 2019

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