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

Primary Purpose

Achondroplasia

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

BMN 111

About this trial

This is an interventional treatment trial for Achondroplasia focused on measuring 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

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children's Hospital & Research Center Oakland
Harbor - UCLA Medical Center
Alfred I. duPont Hospital for Children
Emory University
Ann and Robert H. Lurie Children's Hospital of Chicago
Johns Hopkins University
University of Missouri
Cincinnati Children's Hospital Medical Center
Baylor College of Medicine
Seattle Children's Hospital
Medical College of Wisconsin, Children's Hospital
The Children's Hospital at Westmead
Murdoch Children's Research Institute
Otto-von-Gericke Universitaet, Universitaetskinderklinik
Universitätsklinikum Münster
Osaka University Hospital
Saitama Children's Medical Center
Tokushima University Hospital
Institut Catala de Traumatologica I Medicina de l'Esport
Hospital Sant Joan de Deu
Hospital Universitario Virgen de la Victoria
Acibadem University School of Medicine
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

BMN 111

Arm Description

Outcomes

Primary Outcome Measures

Change from baselines in mean annualized growth velocity

Long term efficacy as measured by change in annualized growth velocity

Secondary Outcome Measures

Changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire

Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire

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 area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)

Characterize the elimination half-life of BMN 111 (t1⁄2)

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)

BMN 111 Activity Biomarkers

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

Evaluate change from baseline in body proportion ratios of the extremities

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

Final Adult Height

Height at 16 years for females and 18 years for males

Full Information

NCT ID

NCT03424018

First Posted

December 28, 2017

Last Updated

June 13, 2023

Sponsor

BioMarin Pharmaceutical

1. Study Identification

Unique Protocol Identification Number

NCT03424018

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 12, 2017 (Actual)

Primary Completion Date

June 2031 (Anticipated)

Study Completion Date

June 2031 (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

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

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

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

119 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BMN 111

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

BMN 111

Other Intervention Name(s)

Vosoritide, Modified recombinant human C-type natriuretic peptide

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baselines in mean annualized growth velocity

Description

Long term efficacy as measured by change in annualized growth velocity

Time Frame

Through study completion, an average of 1 year

Secondary Outcome Measure Information:

Title

Changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire

Time Frame

Through study completion, every 6-12 months

Title

Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire

Time Frame