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An Extension Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

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ClinicalTrials.gov Identifier: NCT03424018
Recruitment Status : Enrolling by invitation
First Posted : February 6, 2018
Last Update Posted : May 30, 2019
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 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : December 2024


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




Primary Outcome Measures :
  1. Change from baselines in mean annualized growth velocity [ Time Frame: Through study completion, an average of 1 year ]
    Long term efficacy as measured by change in annualized growth velocity


Secondary Outcome Measures :
  1. Changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire [ Time Frame: Through study completion, every 6 months ]
  2. Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [ Time Frame: Through study completion, every 6 months ]
  3. Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: Through study completion, every 6 months ]
  4. Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: Through study completion, every 6 months ]
  5. Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: Through study completion, every 6 months ]
  6. Characterize the elimination half-life of BMN 111 (t1⁄2) [ Time Frame: Through study completion, every 6 months ]
  7. Characterize the apparent clearance of drug [ Time Frame: Through study completion, every 6 months ]
  8. Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: Through study completion, every 6 months ]
  9. Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: Through study completion, every 6 months ]
  10. BMN 111 Activity Biomarkers [ Time Frame: Through study completion, every 6 months ]
    BMN 111 activity will be assessed by measuring bone and collagen metabolism

  11. Evaluate change from baseline in body proportion ratios of the extremities [ Time Frame: Through study completion, every 6 months ]
  12. Effect of BMN 111 on bone morphology and quality [ Time Frame: Through study completion, every 6 months for DXA or 2 years for X-ray ]
    The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via X-Ray and Dual X-ray Absorptiometry


Other Outcome Measures:
  1. Evaluate sleep study scores by polysomnography [ Time Frame: Week 260 ]
  2. Optional exploratory genomic biomarker analysis [ Time Frame: Week 260 ]
    Exploratory genomic analysis of genes associated with CNP signaling



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have completed Study 111-301
  • Female >= 10 years old or who have begun menses must have a negative pregnancy test at the Baseline Visit and be willing to have additional pregnancy tests during the study
  • If sexually active, willing to use a highly effective method of contraception while participating in the study
  • Are willing and able to perform all study procedures
  • Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Also, subjects under the age of majority are willing and able to provide written assent (if required by local regulations or the IRB/IEC) after the nature of the study has been explained and prior to performance of any research-related procedure. Subjects who reach the age of majority in their country while the study is ongoing will be asked to provide their own written consent again upon reaching the legal age of majority.

Exclusion Criteria:

  • Permanently discontinued BMN 111 or placebo prior to completion of the 111-301 study
  • Have a clinically significant finding or arrhythmia on Baseline ECG that indicates abnormal cardiac function
  • Evidence of decreased growth velocity (<1.5 cm/year) as assessed over a period of at least 6 months or of growth plate closure (proximal tibia, distal femur) through bilateral lower extremity X-rays.
  • Require any investigational agent prior to completion of study period
  • Current therapy with medications known to alter renal function
  • Pregnant or breastfeeding or plan to become pregnant during study
  • Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason.
  • Have a condition or circumstance that, in the view of the investigator, 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): NCT03424018


Locations
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United States, California
Children's Hospital & Research Center Oakland
Oakland, California, United States, 94609
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Missouri
United States, Missouri
Columbia, Missouri, United States, 65201
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Australia, Victoria
Murdoch Children's Research Institute
Parkville, Victoria, Australia, 3052
United Kingdom
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
BioMarin Pharmaceutical

Additional Information:
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03424018     History of Changes
Other Study ID Numbers: 111-302
2017-002404-28 ( EudraCT Number )
First Posted: February 6, 2018    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioMarin Pharmaceutical:
ACH
Achondroplasia
Bone Diseases
Bone Diseases, Developmental
Dwarfism
Genetic Diseases, Inborn
Musculoskeletal Diseases
Natriuretic Agents
Natriuretic Peptide, C-Type
Osteochondrodysplasias
Physiological Effects of Drugs
Skeletal Dysplasias
Additional relevant MeSH terms:
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Achondroplasia
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Osteochondrodysplasias
Genetic Diseases, Inborn
Natriuretic Peptide, C-Type
Natriuretic Agents
Physiological Effects of Drugs