Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03989947
Recruitment Status : Enrolling by invitation
First Posted : June 18, 2019
Last Update Posted : June 29, 2021
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE May 22, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date June 29, 2021
Actual Study Start Date  ICMJE June 12, 2019
Estimated Primary Completion Date September 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2019)
  • Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: "Through study completion, an average of 5 years" ]
    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 [ Time Frame: "Through study completion, an average of 5 years" ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2019)
  • Evaluate the change from baseline of mean annualized growth velocity (AGV) [ Time Frame: "Through study completion, an average of 5 years" ]
  • Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: "Through study completion, an average of 5 years" ]
  • Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: "Through study completion, an average of 5 years" ]
  • Characterize the elimination half-life of BMN 111 (t½) [ Time Frame: "Through study completion, an average of 5 years" ]
  • Characterize the apparent clearance of drug [ Time Frame: "Through study completion, an average of 5 years" ]
  • Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: "Through study completion, an average of 5 years" ]
  • Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: "Through study completion, an average of 5 years" ]
  • Evaluate the change from baseline on body proportion ratios of the extremities [ Time Frame: "Through study completion, an average of 5 years" ]
  • Effect of BMN 111 on bone morphology and quality by XRay [ Time Frame: "Through study completion, an average of 5 years" ]
  • The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry [ Time Frame: "Through study completion, an average of 5 years" ]
  • Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth [ Time Frame: "Through study completion, an average of 5 years" ]
    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 [ Time Frame: "Through study completion, an average of 5 years" ]
  • Describe the incidence of surgical and medical interventions related to achondroplasia [ Time Frame: "Through study completion, an average of 5 years" ]
  • Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old. [ Time Frame: "Through study completion, an average of 1 year" ]
  • 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. [ Time Frame: "Through study completion, an average of 1 year" ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Extension Study to Evaluate Safety and Efficacy of BMN 111 in Children With Achondroplasia
Official Title  ICMJE A Phase 2 Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Achondroplasia
Intervention  ICMJE Drug: Active BMN 111: Daily subcutaneous injection of 15 ug/kg of BMN 111
Modified recombinant human C-type natriuretic peptide
Other Name: Vosoritide
Study Arms  ICMJE Experimental: Active BMN 111
Age-appropriate daily subcutaneous injections of BMN 111 as determined by the 111-206 study
Intervention: Drug: Active BMN 111: Daily subcutaneous injection of 15 ug/kg of BMN 111
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: June 16, 2019)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2026
Estimated Primary Completion Date September 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Japan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03989947
Other Study ID Numbers  ICMJE 111-208
Has Data Monitoring Committee Not Provided
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  ICMJE Not Provided
Responsible Party BioMarin Pharmaceutical
Study Sponsor  ICMJE BioMarin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director MD BioMarin Pharmaceutical
PRS Account BioMarin Pharmaceutical
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP