Clinical trial NCT03989947: An Extension Study to Evaluate Safety and Efficacy of BMN 111 in Children With Achondroplasia
Official title: A Phase 2 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: PHASE2
Conditions: Achondroplasia
Keywords: Dwarfism
Bone Disease
ACH
Natriuretic Peptide C-Type
Musculoskeletal Diseases
Skeletal Dysplasias
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2019-06-18
Enrollment: 73
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, open-label multi-center long-term extension study, with approximately 70 subjects, to evaluate the safety and efficacy of BMN111 in children with Achondroplasia until subjects reach near-adult final height. Eligible subjects will have completed 1 year of BMN111 or placebo treatment in the 111-206 study and once enrolled in the 111-208 extension study will receive a daily dose of BMN111 by subcutaneous injection according to their age as determined by 111-206.


Eligibility criteria: Inclusion Criteria:

1. Must have completed Study 111-206 on investigational treatment (BMN 111 or placebo).
2. 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.
3. Are willing and able to perform all study procedures

Exclusion Criteria:

1. Permanently discontinued BMN 111 or placebo prior to completion of Study 111-206
2. Have a clinically significant finding or arrhythmia on ECG that indicates abnormal cardiac function or conduction or QTc-F \> 450 msec
3. Require any investigational agent (except BMN 111) prior to completion of study period
4. Current therapy with antihypertensive medications, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, GnRH agonists, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function
5. Pregnant or planning to become pregnant (self or partner) at any time during the study
6. Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason
7. Have a condition or circumstance that, in the view of the investigator, places the subject at high risk for poor treatment compliance

Primary outcomes:
measure: Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: "Through study completion, an average of 5 years"
measure: Evaluate change in height/length z-score in children with ACH treated with BMN 111
timeFrame: "Through study completion, an average of 5 years"
Secondary outcomes:
measure: Evaluate the change from baseline of mean annualized growth velocity (AGV)
timeFrame: "Through study completion, an average of 5 years"
measure: Characterize maximum concentration (Cmax) of BMN 111 in plasma
timeFrame: "Through study completion, an average of 5 years"
measure: Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)
timeFrame: "Through study completion, an average of 5 years"
measure: Characterize the elimination half-life of BMN 111 (t½)
timeFrame: "Through study completion, an average of 5 years"
measure: Characterize the apparent clearance of drug
timeFrame: "Through study completion, an average of 5 years"
measure: Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
timeFrame: "Through study completion, an average of 5 years"
measure: Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
timeFrame: "Through study completion, an average of 5 years"
measure: Evaluate the change from baseline on body proportion ratios of the extremities
timeFrame: "Through study completion, an average of 5 years"
measure: Effect of BMN 111 on bone morphology and quality by XRay
timeFrame: "Through study completion, an average of 5 years"
measure: The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry
timeFrame: "Through study completion, an average of 5 years"
measure: Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth
timeFrame: "Through study completion, an average of 5 years"
measure: BMN 111 activity will be assessed by measuring bone and collagen metabolism
timeFrame: "Through study completion, an average of 5 years"
measure: Describe the incidence of surgical and medical interventions related to achondroplasia
timeFrame: "Through study completion, an average of 5 years"
measure: Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old.
timeFrame: "Through study completion, an average of 1 year"
measure: Evaluate the effect of BMN 111 on skull and brain morphology, including foramen magnum, ventricular and brain parenchymal dimensions by MRI in patients up to 3 years old.
timeFrame: "Through study completion, an average of 1 year"
Other outcomes:
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: Decatur
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann Robert and H. Lurie Children's Hospital of Chicago
state: Illinois
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
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: Osaka
country: Japan
facility: Osaka University
city: Saitama
country: Japan
facility: Saitama Children's Medical Center
city: Tokushima
country: Japan
facility: Tokushima University Hospital
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:
affiliation: BioMarin Pharmaceutical
name: Medical Director MD
role: STUDY_DIRECTOR
References: