Achondroplasia MedDRA version: 20.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 100000004850
Conditions
Interventions
Product Name: Modified recombinant human c-type
Product Code: Natriuretic peptide
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Vosoritide
CAS Number: 1480721-61-5
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Must have completed Study 111-206 (eligible to enroll in 111-208 within 3 months after completing 111-206 at the discretion of the principal investigator and medical monitor). 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 as physically possible Are the trial subjects under 18? yes Number of subjects for this age range: 70 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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, angiotensinconverting 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 (Table 9.3.4.1) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the long-term safety, tolerability of BMN 111 Evaluate change in height/length z-score in children with ACH treated with BMN 111;Secondary Objective: Evaluate the effect of BMN 111 on AGV • Evaluate the pharmacokinetics of BMN 111 • Evaluate the effect of BMN 111 on body proportions and ratios of the extremities • Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA) • Evaluate the long-term effect of BMN 111 on health-related quality of life, developmental status and functional independence , using agespecific QoL and functional independence questionnaires • Evaluate bone metabolism and pharmacodynamic biomarkers • Evaluate immunogenicity of BMN 111 and assess impact on safety, PK, and efficacy measures • 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.;Primary end point(s): •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" ] ;Timepoint(s) of evaluation of this end point: Time Frame: "Through study completion, an average of 5 years" | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •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 (AUC0-8) [ 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 w | — |
Countries
Australia, Japan, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
BioMarin Pharmaceutical Inc.
Outcome results
None listed