Back to results

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

Primary Purpose

Achondroplasia

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Achondroplasia focused on measuring Dwarfism, Bone Disease, ACH, Natriuretic Peptide C-Type, Musculoskeletal Diseases, Skeletal Dysplasias

Eligibility Criteria

15 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Permanently discontinued BMN 111 or placebo prior to completion of Study 111-206
Have a clinically significant finding or arrhythmia on ECG that indicates abnormal cardiac function or conduction or QTc-F > 450 msec
Require any investigational agent (except BMN 111) prior to completion of study period
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
Pregnant or planning to become pregnant (self or partner) at any time during the 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

Sites / Locations

Children's Hospital & Research Center Oakland
Harbor - UCLA Medical Center
Alfred I. duPont Hospital for Children
Emory University
Ann Robert and H. Lurie Children's Hospital of Chicago
Cincinnati Childrens Hospital
Vanderbilt University Medical Center
Baylor College of Medicine
Medical College of Wisconsin, Children's Hospital
The Children's Hospital at Westmead
Murdoch Children's Research Institute
Osaka University
Saitama Children's Medical Center
Tokushima University Hospital
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
Sheffield Children's NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Active BMN 111

Arm Description

Once daily subcutaneous injections of recommended dose of BMN 111 based on weight-band dosing.

Outcomes

Primary Outcome Measures

Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Number of study participants with treatment-emergent adverse events or serious adverse events

Evaluate change in height/length z-score in children with ACH treated with BMN 111

Secondary Outcome Measures

Evaluate the change from baseline of mean annualized growth velocity (AGV)

Characterize maximum concentration (Cmax) of BMN 111 in plasma

Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)

Characterize the elimination half-life of BMN 111 (t½)

Characterize the apparent clearance of drug

Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)

Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)

Evaluate the change from baseline on body proportion ratios of the extremities

Effect of BMN 111 on bone morphology and quality by XRay

The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry

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]).

BMN 111 activity will be assessed by measuring bone and collagen metabolism

Describe the incidence of surgical and medical interventions related to achondroplasia

Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old.

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.

Full Information

NCT ID

NCT03989947

First Posted

May 22, 2019

Last Updated

August 1, 2023

Sponsor

BioMarin Pharmaceutical

1. Study Identification

Unique Protocol Identification Number

NCT03989947

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 12, 2019 (Actual)

Primary Completion Date

September 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Achondroplasia

Keywords

Dwarfism, Bone Disease, ACH, Natriuretic Peptide C-Type, Musculoskeletal Diseases, Skeletal Dysplasias

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

73 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active BMN 111

Arm Type

Experimental

Arm Description

Once daily subcutaneous injections of recommended dose of BMN 111 based on weight-band dosing.

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

Vosoritide

Intervention Description

Modified recombinant human C-type natriuretic peptide (subject to adjustment per protocol)

Primary Outcome Measure Information:

Title

Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Description

Number of study participants with treatment-emergent adverse events or serious adverse events

Time Frame