Achondroplasia MedDRA version: 25.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Voxzogo
Product Name: modified recombinant human C-type natriuretic peptide
Product Code: BMN 111
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: vosoriti
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have completed Study 111-301 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. Females = 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 4. If sexually active, are willing to use contraception as specified in section 9.3.3 of the protocol, 5. Are willing and able to perform all study procedures Are the trial subjects under 18? yes Number of subjects for this age range: 119 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 111-301 2. Have a clinically significant finding or arrhythmia on Baseline electrocardiogram (ECG) that indicates abnormal cardiac function or conduction or QTc-F > 450 msec 3. Evidence of decreased growth velocity (AGV < 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 including both AP and lateral views 4. Require any investigational agent prior to completion of study period 5. 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 (Table 9.3.2.1) 6. Planned or expected to have limb-lengthening surgery during the study period 7. Pregnant or breastfeeding at the Baseline Visit or planning to become pregnant (self or partner) at any time during the study 8. Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason 9. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this extension study is to: - Evaluate the long-term safety, tolerability, and efficacy for growth in children with ACH treated with BMN 111;Secondary Objective: The secondary objectives of the study are to: •Evaluate the pharmacokinetics of BMN 111 •Evaluate immunogenicity of BMN 111 and assess impact on safety, PK, and efficacy measures •Evaluate body proportion ratios of the extremities •Evaluate effect of BMN 111 on bone morphology/quality by X-ray and DXA •Evaluate changes in health-related quality of life as measured the Quality of Life in Short Stature Youth (QoLISSY) and the PedsQL questionnaires •Evaluate changes in functional independence as measured by the Wee FIM clinician-reported outcome •Evaluate change from baseline in bone metabolism biomarkers •To evaluate the effect of BMN 111 on final adult height;Primary end point(s): The primary efficacy endpoint is the change from baseline in annualized growth velocity (AGV). Safety will be evaluated by the incidence of AEs, SAEs, and clinically significant changes in vital signs, physical examination, Tanner stage, ECG, echocardiogram, bone morphology/quality assessed by X-rays/DXA, and laboratory test results (urinalysis, chemistry, hematology). Additionally, imaging, hip monitoring, immunogenicity, salivary cortisol, serum prolactin, and FSH/LH levels (FSH/LH will be monitored for all subjects >8 years of age, and for subjects at Tanner stage 2, whichever is earlier); and anxiety, motor and cognitive assessment with the Childhood Behavioral Checklist (CBCL) and WeeFIM will be utilized for safety-related reviews and analysis. Additional assessments will be conducted to evaluate changes from baseline in bone metabolism and BMN 111 activity biomarkers.;Timepoint(s) of evaluation of this end point: Anthropometric measurements: 111-301 Week52/302 BL, Weeks 13, 26,39, 52, 65, 78, 91, 104, every 26 weeks up to 260 Clinical labs; Vital signs/AEs; Physical exam; ECG; Anti- | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1)The secondary efficacy endpoints include the change from baseline in height [Z-score], height, final adult height, a and the change from baseline in upper:lower body segment ratio. 2)PK sampling will be carried out over the study period. 3)Health-related Quality of Life (HRQoL) and ADL questionnaires will be administered to assess quality of life and daily activities performance of study subjects. 4) Evaluate immunogenicity of BMN 111 and assess impact on safety,PK and efficacy measures 5) Evaluate change from baseline in body proportion ratios of the extremities 6) Evaluate effect of BMN 111 on bone morphology/quality by X-ray and DXA ;Timepoint(s) of evaluation of this end point: Anthropometric measurements: 111-301 Week 52/302 BL, Weeks 13, 26, 39, 52, 65, 78, 91, 104, every 26 weeks up to Week 260 PK: 301 Week 52/302 BL, Day 1, Week 26, Week 52, Week 78, Week 104, every 26 weeks up to Week 260 Health-related Quality of Life (PedsQL, QoLISSY), Functional Independence Assessment (Wee FIM), and CBCL: 111-301 Week 52/302 BL, Week 26, Week 52, Week 78, Week 104, every 26 weeks up to Week 260 DXA (BMD and BMC of whole body less head, spine): Week 52/302 BL, Week 52, Week 104, Week 156, Week 208, Week 260 Anti-BMN 111 immunogenicity: Week 52/302 BL, Day 1. Week 13, Week 26, Week 39, Week 52, Week 65, Week 78, Week 91, Week 104, every 26 week up to Week 260 | — |
Countries
Australia, Germany, Japan, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
BioMarin Pharmaceutical Inc.
Outcome results
None listed