VOSORITIDE for Achondroplasia

Inclusion criteria

• {"criterion_text":"- Must have completed Study 111-301\n- 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.\n- 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\n- If sexually active, are willing to use contraception as specified in section 9.3.3 of the protocol\n- Are willing and able to perform all study procedures"}

Exclusion criteria

• {"criterion_text":"- Permanently discontinued BMN 111 or placebo prior to completion of Study 111-301\n- Have a clinically significant finding or arrhythmia on Baseline electrocardiogram (ECG) that indicates abnormal cardiac function or conduction or QTc-F > 450 msec\n- 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\n- Require any investigational agent prior to completion of study period\n- 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)\n- Planned or expected to have limb-lengthening surgery during the study period\n- Pregnant or breastfeeding at the Baseline Visit or planning to become pregnant (self or partner) at any time during the study\n- Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason\n- 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"}

Primary endpoints

• {"endpoint_text":"- 1)Key efficacy endpoints: a)Change from baseline in AGV b) Change from baseline in height Z-score c)Change from baseline in upper to lower body segment ratio","definition_or_measurement_approach":"Change from baseline measurements: a) Annualized growth velocity (AGV); b) Height Z-score change from baseline; c) Upper to lower body segment ratio change from baseline (measured by anthropometry/imaging as specified in protocol)."}
• {"endpoint_text":"- 2)Safety assessments: Incidence, severity, and relationship to study drug of all treatment-emergent adverse events (TEAEs).","definition_or_measurement_approach":"Safety assessed by recording all TEAEs with incidence, severity and investigator-assessed relationship to study drug."}
• {"endpoint_text":"- 3)Procedures/ interventions/ surgeries, imaging assessments, clinical laboratory assessments, Child Behavior Checklist (CBCL), vital signs, electrocardiogram (ECG), and hip clinical assessment.","definition_or_measurement_approach":"Collection of procedures/interventions, imaging (X-ray, DXA), laboratory assessments, CBCL clinician- or parent-reported scores, vital signs, ECG readings, and hip clinical assessments as specified in the protocol."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in: 1)Upper Arm Length to Lower Arm (Forearm), Length Ratio","definition_or_measurement_approach":"Change from baseline in anatomical length ratios measured by anthropometry/imaging."}
• {"endpoint_text":"- 2)Upper Leg Length (Thigh) to Knee to Heel Length Ratio","definition_or_measurement_approach":"Change from baseline in anatomical length ratios measured by anthropometry/imaging."}
• {"endpoint_text":"- 3)Upper Leg Length (Thigh) to Tibial Length Ratio","definition_or_measurement_approach":"Change from baseline in anatomical length ratios measured by anthropometry/imaging."}
• {"endpoint_text":"- 4)Arm Span to Standing Height Ratio","definition_or_measurement_approach":"Change from baseline in arm span versus standing height ratio measured anthropometrically."}
• {"endpoint_text":"- 5)Bone age, bone age Z-score, bone mineral density, (BMD), BMD Z-score, and bone mineral content (BMC)","definition_or_measurement_approach":"Bone age and Z-score by radiographic assessment; BMD and BMC measured by DXA with Z-scores."}
• {"endpoint_text":"- 6)QoLISSY and PedsQL domain and total scores","definition_or_measurement_approach":"Health-related quality of life measured using QoLISSY and PedsQL questionnaires (domain and total scores)."}

Germany

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

28-03-2025

Processing Time Days

368

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

14-03-2025

Processing Time Days

354

Number Of Sites

3

Number Of Participants

12

Primary sponsor

Full Name

BioMarin Pharmaceutical Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Laboratory Services Inc.

Responsibilities

Urinanalysis

Name

Pra International

Responsibilities

medical image analysis, review x-ray, MRI, ultrasound

Name

Precision For Medicine Inc.

Responsibilities

sample storage

Name

Eurofins Viracor Biopharma Services Inc.

Third parties

• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Urinanalysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pra International","duties_or_roles":"medical image analysis, review x-ray, MRI, ultrasound","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eurofins Viracor Biopharma Services Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}