Achondroplasia MedDRA version: 20.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 100000004850
Conditions
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of ACH, confirmed by genetic testing. If subjects had previous genetic testing, subjects must have a lab report from a certified laboratory with the study specific mutation documented. 2. Age 0 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.) 2. Subject weighs 2 mg/dL - Chronic anemia or Hgb 450 msec on screening ECG 6. Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator and informed on the following assessments: - Physical exam (e.g., neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins) - Polysomnography (e.g., severe central sleep apnea) - MRI indicating presence of severe CMC or spinal cord damage 7. Have an unstable medical condition likely to require surgical intervention in the next 6 months, or planned spine or long-bone surgery (i.e., surgery involving significant disruption of bone cortex) during the study period 8. Have documented uncorrected Vitamin D deficiency: 25(OH)D = 15 ng/mL (37.5 nmol/L) 9. Require any other investigational product prior to completion of the study period 10. Have received another investigational product or investigational medical device within 30 days prior to the Screening visit 11. Have used any other investigational product or investigational medical device for the treatment of achondroplasia or short stature at any time 12. Require current chronic therapy with antihypertensive medication or any medication that, in the investigator’s judgment, may compromise the safety or ability of the subject to participate in this clinical study 13. Have been treated with growth hormone, insulin-like grow
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are to: - Evaluate the safety and tolerability of BMN 111 in children age 0 to < 60 months with ACH - Evaluate the effect of BMN 111 on change from baseline in length/ height Z-score ; Secondary Objective: - Evaluate the effect of BMN 111 on change from baseline in AGV throughout the 52 weeks of the study - Evaluate the effect of BMN 111 on bone morphology/quality by x-ray and dual x-ray absorptiometry (DXA) - Evaluate the PK of BMN 111 in children age 0 to < 60 months with ACH - Evaluate hip function - Evaluate for hip, thigh, or knee pain, or change in gait from medical history - Evaluate the effect of BMN 111 on health related quality of life (HRQol), developmental status, and functional using age-specific QoL and functional independence questionnaires (Bayley-Scales of Infant and Toddler Development, Third eddition [Bayley III], Activity of Daily Living and Functional Independence Meaure (Wee-FIM), Infant Toddler Quality of Life Questionnaire (ITQOL), Child Behavior Checklist [CBCL] - Evaluate immunogenicity of BMN 111 and assess impact on safety, PK, and efficacy measures - Evaluate the effect of BMN 111 on bone metabolism and BMN 111 pharmacodynamic biomarkers ; Primary end point(s): - To assess the safety and tolerability of daily SC BMN 111 administered in children age 0 to < 60 months with ACH - To evaluate the effect of BMN 111 on length/height Z-score. ; Timepoint(s) of evaluation of this end point: -Duration of trial -Anthropometric Measurement: Screening/ Baseline, Day 1, Week 6, Week 13, Week 26, Week 39, Week 52 -Imaging assessments (X-rays of the spine and entire lower extremities, DXA of total b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints include: 1) Change from baseline in AGV (annualized to cm/yr), 2) Change from baseline in bone morphology/quality, 3) PK sampling, 4) hip function, 5) hip, thigh, or knee pain, or change in gait from medical history, 6) developmental/functional/QOL status 7) Evaluate immunogenicity of BMN 111 8) Biomarker samples to evaluate the effect of BMN 111 on bone metabolism and BMN 111 pharmacodynamic biomarkers. Growth parameters and body proportions, sleep apnea, skull and brain morphology, and clinical outcome assessments (developmental/functional/HRQoL status). ; Timepoint(s) of evaluation of this end point: 1) Anthropometric Measurement: Screening/ Baseline, Day 1, Week 6, Week 13, Week 26, Week 39, Week 52 2) DXA and AP and lateral X-rays: Screening/ Baseline, Week 52 3) Day 1, Week 13, Week 26, Week 39, Week 52 4) Screening/ Baseline, Week 26, Week 52 5) Screening/ Baseline, Day 1, Day 2, Day 3, Day 8, Week 3, Week 6, Week 13, Week 20, Week 26, Week 39, Week 52, Week 56 6) Screening/ Baseline, Week 26, Week 52 7) Day 1, Week 13, Week 26, Week 52 8) - Blood and urine biomarkers: Screening/ Baseline, Day 1, Day 2, Day 3, Day 8, Week 3, Week 6, Week 13, Week 20, Week 26, Week 39, Week 52 - Biomarker samples (optional): Week 6 and Week 52 | — |
Countries
Australia, Japan, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
BioMarin Pharmaceutical Inc.
Outcome results
None listed