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Trial record 4 of 13 for:    achondroplasia

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 : Enrolling by invitation
First Posted : June 23, 2017
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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.

Condition or disease Intervention/treatment Phase
Achondroplasia Drug: BMN 111 Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
Actual Study Start Date : December 12, 2016
Estimated Primary Completion Date : October 2019


Arm Intervention/treatment
Experimental: Active BMN 111
Daily subcutaneous injection of 15 micrograms per kilogram BMN111
Drug: BMN 111
Subcutaneous injection of 15 μg/kg of BMN 111 daily
Other Names:
  • Vosoritide
  • Modified recombinant human C-type natriuretic peptide

Placebo Comparator: Placebo
Daily subcutaneous injection of placebo
Drug: Placebo
Subcutaneous injection of 15 μg/kg of placebo daily




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: 54 weeks ]
    The number of subjects who reported at least one adverse event

  4. Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: 52 weeks ]
  5. Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: 52 weeks ]
  6. Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: 52 weeks ]
  7. Characterize the elimination half-life of BMN 111 (t½) [ Time Frame: 52 weeks ]
  8. Characterize the apparent clearance of drug [ Time Frame: 52 weeks ]
  9. Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: 52 weeks ]
  10. Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: 52 weeks ]
  11. 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


Other Outcome Measures:
  1. Change from baseline in body proportion ratios of the extremities in subjects [ Time Frame: one year ]
  2. 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

  3. Optional exploratory genomic biomarker analysis [ Time Frame: Weeks 6 and 52 ]
    Exploratory genomic analysis of genes associated with CNP signaling

  4. Optional sleep study scores by polysomnography in a subset of subjects [ Time Frame: Screening and week 52 ]
  5. 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 ]
  6. Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [ Time Frame: Screening, weeks 26 and 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Parent(s) or guardian(s) consent
  • 5 to < 17 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
  • Cardiac or vascular disease
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03197766


  Hide Study Locations
Locations
United States, California
Children's Hospital & Research Center Oakland
Oakland, California, United States, 94609
Harbor - UCLA Medical Center
Torrance, California, United States, 90509
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University, Riley Children's Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65201
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United States, Wisconsin
Medical College of Wisconsin, Children's Hospital
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
The Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Murdoch Children's Research Institute
Parkville, Victoria, Australia, 3052
Germany
Otto-von-Guericke Universitaet, Universitaetskinderklinik
Magdeburg, Germany, 39120
Universitätsklinikum Münster
Münster, Germany, 48149
Japan
Osaka University Hospital
Osaka, Japan
Saitama Children's Medical Center
Saitama, Japan
Tokushima University Hospital
Tokushima, Japan
Spain
Institut Catala de Traumatologica I Medicina de l'Esport
Barcelona, Spain, 08028
Hospital Sant Joan de Deu
Barcelona, Spain, 08950
Hospital Universitario Virgen de la Victoria
Málaga, Spain, 29010
Turkey
Acibadem University School of Medicine
Istanbul, Turkey, 34752
United Kingdom
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
London, United Kingdom, SE1 9RT
Sheffield Children's NHS Foundation Trust
Sheffield, United Kingdom, S10 2TH
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Medical Director, MD BioMarin Pharmaceutical

Additional Information:
Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03197766     History of Changes
Other Study ID Numbers: 111-301
2015-003836-11 ( EudraCT Number )
First Posted: June 23, 2017    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioMarin Pharmaceutical:
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

Additional relevant MeSH terms:
Achondroplasia
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Osteochondrodysplasias
Genetic Diseases, Inborn
Natriuretic Peptide, C-Type
Natriuretic Agents
Physiological Effects of Drugs