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

Sponsor

BioMarin Pharmaceutical (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04554940

Collaborator

(none)

Enrollment

Locations

Arms

73.7

Anticipated Duration (Months)

6.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Achondroplasia	Biological: vosoritide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 10, 2020

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Vosoritide + Standard of Care

Standard of Care treatment for cervicomedullary compression and once daily subcutaneous injection of recommended dose of vosoritide based on weight-band dosing.

Biological: vosoritide

Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.

No Intervention: Standard of Care Alone

Institutional standard of care monitoring and treatment for cervicomedullary compression

Outcome Measures

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Through Week 260]

Secondary Outcome Measures

Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software [Through Week 260]

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Months to 12 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Murdoch Children's Research Institute	Parkville	Victoria	Australia	3052
2	Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital	London		United Kingdom	SE1 7EH
3	Sheffield Children's NHS Foundation Trust	Sheffield		United Kingdom	S10 2TH