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

• ClinicalTrials.gov Identifier: NCT03424018
• Recruitment Status: Active, not recruiting
• First Posted: February 6, 2018
• Last Update Posted: December 12, 2022
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

Tracking Information

• First Submitted Date: December 28, 2017
• First Posted Date: February 6, 2018
• Last Update Posted Date: December 12, 2022
• Actual Study Start Date: December 12, 2017
• Estimated Primary Completion Date: June 2031 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2018)

Change from baselines in mean annualized growth velocity [ Time Frame: Through study completion, an average of 1 year ]

Long term efficacy as measured by change in annualized growth velocity

Original Primary Outcome Measures (submitted: January 31, 2018)

Change from baselines in mean annualized growth velocity [ Time Frame: Up to 5 years or near final adult height ]

Long term efficacy as measured by change in annualized growth velocity

Current Secondary Outcome Measures (submitted: June 30, 2022)

• 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 ]
• Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [ Time Frame: Through study completion, every 12 months ]
• Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: Through study completion, every 12 months ]
• Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: Through study completion, every 12 months ]
• Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: Through study completion, every 12 months ]
• Characterize the elimination half-life of BMN 111 (t1⁄2) [ Time Frame: Through study completion, every 12 months ]
• Characterize the apparent clearance of drug [ Time Frame: Through study completion, every 12 months ]
• Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: Through study completion, every 12 months ]
• Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: Through study completion, every 12 months ]
• BMN 111 Activity Biomarkers [ Time Frame: Through study completion, every 12 months ]
  BMN 111 activity will be assessed by measuring bone and collagen metabolism
• Evaluate change from baseline in body proportion ratios of the extremities [ Time Frame: Through study completion, every 6 months ]
• Effect of BMN 111 on bone morphology and quality [ Time Frame: Through study completion, every 12 months for DXA or 2 years for X-ray ]
  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 [ Time Frame: Up to at least 16 years of age for females and 18 years of age for males ]
  Height at 16 years for females and 18 years for males

Original Secondary Outcome Measures (submitted: January 31, 2018)

• Potential 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 months ]
• Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [ Time Frame: Through study completion, every 6 months ]
• Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: Through study completion, every 6 months ]
• Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: Through study completion, every 6 months ]
• Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: Through study completion, every 6 months ]
• Characterize the elimination half-life of BMN 111 (t1⁄2) [ Time Frame: Through study completion, every 6 months ]
• Characterize the apparent clearance of drug [ Time Frame: Through study completion, every 6 months ]
• Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: Through study completion, every 6 months ]
• Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: Through study completion, every 6 months ]

Current Other Pre-specified Outcome Measures (submitted: June 30, 2022)

Optional exploratory genomic biomarker analysis [ Time Frame: Once through study completion ]

Exploratory genomic analysis of genes associated with CNP signaling

Original Other Pre-specified Outcome Measures (submitted: January 31, 2018)

• Evaluate sleep study scores by polysomnography [ Time Frame: Week 260 ]
• Evaluate change from baseline in body proportion ratios of the extremities [ Time Frame: Through study completion, every 6 months ]
• BMN 111 Activity Biomarkers [ Time Frame: Through study completion, every 6 months ]
  BMN 111 activity will be assessed by measuring bone and collagen metabolism
• Optional exploratory genomic biomarker analysis [ Time Frame: Week 260 ]
  Exploratory genomic analysis of genes associated with CNP signaling
• Effect of BMN 111 on bone morphology and quality [ Time Frame: Through study completion, every 6 months ]
  The effect of BMN 111 on bone morphology will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry

Descriptive Information

• 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Achondroplasia

Intervention

Drug: BMN 111

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

Other Names:

• Vosoritide
• Modified recombinant human C-type natriuretic peptide

Study Arms

Experimental: BMN 111

Intervention: Drug: BMN 111

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 9, 2019): 119
• Original Estimated Enrollment (submitted: January 31, 2018): 110
• Estimated Study Completion Date: June 2031
• Estimated Primary Completion Date: June 2031 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Germany, Japan, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03424018
• Other Study ID Numbers: 111-302; 2017-002404-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioMarin Pharmaceutical
• Original Responsible Party: Same as current
• Current Study Sponsor: BioMarin Pharmaceutical
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BioMarin Pharmaceutical
• Verification Date: December 2022