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

Achondroplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03424018
• Other study ID #: 111-302
• Secondary ID: 2017-002404-28
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 12, 2017
• Est. completion date: June 2031

Study information

• Verified date: December 2023
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 119
• Est. completion date: June 2031
• Est. primary completion date: June 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Achondroplasia

Intervention

Drug:
• BMN 111
Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.

Locations

Country	Name	City	State
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Germany	Otto-von-Gericke Universitaet, Universitaetskinderklinik	Magdeburg
Germany	Universitätsklinikum Münster	Münster
Japan	Osaka University Hospital	Osaka
Japan	Saitama Children's Medical Center	Saitama
Japan	Tokushima University Hospital	Tokushima
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Institut Catala de Traumatologica I Medicina de l'Esport	Barcelona
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Turkey	Acibadem University School of Medicine	Istanbul
United Kingdom	Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital	London
United Kingdom	Sheffield Children's NHS Foundation Trust	Sheffield
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Missouri	Columbia	Missouri
United States	Baylor College of Medicine	Houston	Texas
United States	Medical College of Wisconsin, Children's Hospital	Milwaukee	Wisconsin
United States	Children's Hospital & Research Center Oakland	Oakland	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Harbor - UCLA Medical Center	Torrance	California
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Japan,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Optional exploratory genomic biomarker analysis	Exploratory genomic analysis of genes associated with CNP signaling	Once through study completion
Primary	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	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
Secondary	Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire		Through study completion, every 12 months
Secondary	Characterize maximum concentration (Cmax) of BMN 111 in plasma		Through study completion, every 12 months
Secondary	Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8)		Through study completion, every 12 months
Secondary	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
Secondary	Characterize the elimination half-life of BMN 111 (t1/2)		Through study completion, every 12 months
Secondary	Characterize the apparent clearance of drug		Through study completion, every 12 months
Secondary	Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)		Through study completion, every 12 months
Secondary	Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)		Through study completion, every 12 months
Secondary	BMN 111 Activity Biomarkers	BMN 111 activity will be assessed by measuring bone and collagen metabolism	Through study completion, every 12 months
Secondary	Evaluate change from baseline in body proportion ratios of the extremities		Through study completion, every 6 months
Secondary	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
Secondary	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

External Links

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