Clinical trial NCT03424018: An Extension Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
Official title: A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Achondroplasia
Keywords: 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
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2018-02-06
Enrollment: 119
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Change from baselines in mean annualized growth velocity
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire
timeFrame: Through study completion, every 6-12 months
measure: Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire
timeFrame: Through study completion, every 12 months
measure: Characterize maximum concentration (Cmax) of BMN 111 in plasma
timeFrame: Through study completion, every 12 months
measure: Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)
timeFrame: Through study completion, every 12 months
measure: Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
timeFrame: Through study completion, every 12 months
measure: Characterize the elimination half-life of BMN 111 (t1⁄2)
timeFrame: Through study completion, every 12 months
measure: Characterize the apparent clearance of drug
timeFrame: Through study completion, every 12 months
measure: Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
timeFrame: Through study completion, every 12 months
measure: Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
timeFrame: Through study completion, every 12 months
measure: BMN 111 Activity Biomarkers
timeFrame: Through study completion, every 12 months
measure: Evaluate change from baseline in body proportion ratios of the extremities
timeFrame: Through study completion, every 6 months
measure: Effect of BMN 111 on bone morphology and quality
timeFrame: Through study completion, every 12 months for DXA or 2 years for X-ray
measure: Final Adult Height
timeFrame: Up to at least 16 years of age for females and 18 years of age for males
Other outcomes:
measure: Optional exploratory genomic biomarker analysis
timeFrame: Once through study completion
Locations:
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Medical Center
state: California
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Children's Hospital
state: Wisconsin
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Magdeburg
country: Germany
facility: Otto-von-Gericke Universitaet, Universitaetskinderklinik
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Saitama
country: Japan
facility: Saitama Children's Medical Center
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Barcelona
country: Spain
facility: Institut Catala de Traumatologica I Medicina de l'Esport
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Istanbul
country: Turkey
facility: Acibadem University School of Medicine
city: London
country: United Kingdom
facility: Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's NHS Foundation Trust
Study officials:
References: