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

A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia

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

Study Overview

• Status: Active, not recruiting
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: BMN 111

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• Germany
  • Magdeburg, Germany, 39120
    • Otto-von-Gericke Universitaet, Universitaetskinderklinik
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
• Japan
  • Osaka, Japan
    • Osaka University Hospital
  • Saitama, Japan
    • Saitama Children's Medical Center
  • Tokushima, Japan
    • Tokushima University Hospital
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Deu
  • Barcelona, Spain, 08028
    • Institut Catala de Traumatologica I Medicina de l'Esport
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
• Turkey
  • Istanbul, Turkey, 34752
    • Acibadem University School of Medicine
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's NHS Foundation Trust
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland
    • Torrance, California, United States, 90509
      • Harbor - UCLA Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. DuPont Hospital for Children
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMN 111	Drug: BMN 111; Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.; Other Names: Vosoritide; Modified recombinant human C-type natriuretic peptide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baselines in mean annualized growth velocity	Long term efficacy as measured by change in annualized growth velocity	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire		Through study completion, every 6-12 months
Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire		Through study completion, every 12 months
Characterize maximum concentration (Cmax) of BMN 111 in plasma		Through study completion, every 12 months
Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)		Through study completion, every 12 months
Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)		Through study completion, every 12 months
Characterize the elimination half-life of BMN 111 (t1⁄2)		Through study completion, every 12 months
Characterize the apparent clearance of drug		Through study completion, every 12 months
Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)		Through study completion, every 12 months
Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)		Through study completion, every 12 months
BMN 111 Activity Biomarkers	BMN 111 activity will be assessed by measuring bone and collagen metabolism	Through study completion, every 12 months
Evaluate change from baseline in body proportion ratios of the extremities		Through study completion, every 6 months
Effect of BMN 111 on bone morphology and quality	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	Through study completion, every 12 months for DXA or 2 years for X-ray
Final Adult Height	Height at 16 years for females and 18 years for males	Up to at least 16 years of age for females and 18 years of age for males

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optional exploratory genomic biomarker analysis	Exploratory genomic analysis of genes associated with CNP signaling	Once through study completion

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Publications and helpful links

Helpful Links

• U.S. FDA Resources
• NIH Genetics Home Reference related topics: Achondroplasia
• Description NIH Genetic and Rare Diseases Information Center resources: Achondroplasia

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2017
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: December 28, 2017
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Physiological Effects of Drugs; Bone Diseases; Bone Diseases, Developmental; Achondroplasia; Dwarfism; ACH; Skeletal Dysplasias; Natriuretic Agents; Natriuretic Peptide, C-Type
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, C-Type
• Other Study ID Numbers: 111-302; 2017-002404-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No