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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Achondroplasia
• Intervention / Treatment: Biological: vosoritide

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Musculoskeletal Diseases; Bone Diseases; Dwarfism; Natriuretic Peptide, C-Type; Bone Diseases, Developmental ACH
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia
• Other Study ID Numbers: 111-209

Drug and device information, study documents

• 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