A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia

Study Overview
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Brief Summary
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Study 111-209 is a Phase 2 randomized, open-label clinical trial of BMN 111 in infants and young children with a diagnosis of Achondroplasia at a heightened risk of requiring cervicomedullary decompression surgery

Official Title
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A Randomized, Controlled, Open-label Clinical Trial With an Open-label Extension to Investigate the Safety of Vosoritide in Infants and Young Children With Achondroplasia at Risk of Requiring Cervicomedullary Decompression Surgery

Conditions
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Achondroplasia

Intervention / Treatment
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* Biological: vosoritide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent(s) or guardian(s) willing and able to provide signed informed consent after the nature of the study has been explained and prior to performance of any research related procedure. Have ACH, documented by genetic testing. Are willing and able to perform all study procedures as physically possible. Age 0 to ≤ 12 months, at study entry (Day 1). Given that any potential impact of vosoritide therapy on the foramen magnum is dependent on treating as early as possible and as long as possible while the synchondroses at the base of the skull are still open. For subjects > 6 months of age at enrollment, a discussion between the investigator and the Medical Monitor should occur with the goal of limiting the number of subjects in the range of > 6 months to ≤ 12 months of age. Parent(s) or caregiver(s) are willing to administer daily injections to the subject and complete the required training. Have evidence of CMC that may require surgical intervention Exclusion Criteria: Have hypochondroplasia or short-stature condition other than achondroplasia (eg, trisomy 21, pseudoachondroplasia, etc). Have CMC that either does not require surgical intervention (for example foramen magnum narrowing with preservation of the cerebrospinal fluid space) or does require immediate surgical intervention . Have any of the following: Untreated congenital hypothyroidism or maternal history of hyperthyroidism, Insulin-requiring neonatal diabetes mellitus, Autoimmune inflammatory disease, Inflammatory bowel disease, Autonomic neuropathy. Have a history of any of the following:Renal insufficiency, Chronic anemia,Baseline systolic blood pressure below age and gender specified normal range or recurrent symptomatic hypotension (defined as episodes of low blood pressure generally accompanied by symptoms eg, pallor, cyanosis, irritability, poor feeding) and Cardiac or vascular disease. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F ≥ 450 msec on screening ECG. Have been treated with growth hormone, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time. Have ever had prior cervicomedullary decompression surgery. Have had a fracture of the long bones or spine within 6 months prior to Screening.

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vosoritide + Standard of Care<br>Standard of Care treatment for cervicomedullary compression and once daily subcutaneous injection of recommended dose of vosoritide based on weight-band dosing. | Biological: vosoritide<br>* Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.<br>|
| No Intervention: Standard of Care Alone<br>Institutional standard of care monitoring and treatment for cervicomedullary compression | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] |  | Through Week 260 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software |  | Through Week 260 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dwarfism, Bone Diseases, Bone Diseases, Developmental ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases