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

• ClinicalTrials.gov Identifier: NCT04554940
• Recruitment Status: Active, not recruiting
• First Posted: September 18, 2020
• Last Update Posted: December 22, 2022
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

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 (Clinical Trial)
• 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: October 10, 2020
• Estimated Primary Completion Date: December 2027
• Estimated Study Completion Date: December 2027

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Through Week 260 ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 0 Months to 12 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Australia, Victoria

Murdoch Children's Research Institute

Parkville, Victoria, Australia, 3052

United Kingdom

Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital

London, United Kingdom, SE1 7EH

Sheffield Children's NHS Foundation Trust

Sheffield, United Kingdom, S10 2TH

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

• Study Director: Medical Director, MD; BioMarin Pharmaceutical

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Savarirayan R, Irving M, Maixner W, Thompson D, Offiah AC, Connolly DJ, Raghavan A, Powell J, Kronhardt M, Jeha G, Ghani S, Fisheleva E, Day JR. Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery. Sci Prog. 2021 Jan-Mar;104(1):368504211003782. doi: 10.1177/00368504211003782.

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT04554940
• Other Study ID Numbers: 111-209
• First Posted: September 18, 2020
• Last Update Posted: December 22, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by BioMarin Pharmaceutical:

Dwarfism; Bone Diseases; Bone Diseases, Developmental ACH; Natriuretic Peptide, C-Type; Musculoskeletal Diseases

Additional relevant MeSH terms:

Achondroplasia; Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn