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

Achondroplasia Clinical Trial

Official title:

A Phase 2 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: NCT03989947
• Other study ID #: 111-208
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 12, 2019
• Est. completion date: December 2026

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 73
• Est. completion date: December 2026
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Achondroplasia

Intervention

Drug:
• Active BMN 111: Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.
Modified recombinant human C-type natriuretic peptide (subject to adjustment per protocol)

Locations

Country	Name	City	State
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Japan	Osaka University	Osaka
Japan	Saitama Children's Medical Center	Saitama
Japan	Tokushima University Hospital	Tokushima
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	Ann Robert and H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Childrens Hospital	Cincinnati	Ohio
United States	Emory University	Decatur	Georgia
United States	Baylor College of Medicine	Houston	Texas
United States	Medical College of Wisconsin, Children's Hospital	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital & Research Center Oakland	Oakland	California
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,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Number of study participants with treatment-emergent adverse events or serious adverse events	"Through study completion, an average of 5 years"
Primary	Evaluate change in height/length z-score in children with ACH treated with BMN 111		"Through study completion, an average of 5 years"
Secondary	Evaluate the change from baseline of mean annualized growth velocity (AGV)		"Through study completion, an average of 5 years"
Secondary	Characterize maximum concentration (Cmax) of BMN 111 in plasma		"Through study completion, an average of 5 years"
Secondary	Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8)		"Through study completion, an average of 5 years"
Secondary	Characterize the elimination half-life of BMN 111 (t½)		"Through study completion, an average of 5 years"
Secondary	Characterize the apparent clearance of drug		"Through study completion, an average of 5 years"
Secondary	Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)		"Through study completion, an average of 5 years"
Secondary	Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)		"Through study completion, an average of 5 years"
Secondary	Evaluate the change from baseline on body proportion ratios of the extremities		"Through study completion, an average of 5 years"
Secondary	Effect of BMN 111 on bone morphology and quality by XRay		"Through study completion, an average of 5 years"
Secondary	The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry		"Through study completion, an average of 5 years"
Secondary	Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth	Evaluate the long-term effect of BMN 111 on health-related quality of life, developmental status and functional independence, using age-specific QoL and functional independence questionnaires (Bayley-III, WeeFIM, ITQOL, QoLISSY, PedsQL, Child Behavior Checklist 1.5-5 [CBCL 1.5-5], Child Behavior Checklist 6-18 [CBCL 6-18]).	"Through study completion, an average of 5 years"
Secondary	BMN 111 activity will be assessed by measuring bone and collagen metabolism		"Through study completion, an average of 5 years"
Secondary	Describe the incidence of surgical and medical interventions related to achondroplasia		"Through study completion, an average of 5 years"
Secondary	Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old.		"Through study completion, an average of 1 year"
Secondary	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.		"Through study completion, an average of 1 year"