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

NCT04554940 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 111-209
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 3

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

Conditions

Achondroplasia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Through Week 260

Secondary Outcomes (1)

• Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software

  Through Week 260

Study Arms (2)

Vosoritide + Standard of Care

EXPERIMENTAL

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

Biological: vosoritide

Standard of Care Alone

NO INTERVENTION

Institutional standard of care monitoring and treatment for cervicomedullary compression

Interventions

vosoritide BIOLOGICAL

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

Vosoritide + Standard of Care

Eligibility Criteria

• Age: 0 Months - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (3)

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

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

London, SE1 7EH, United Kingdom

Location

Sheffield Children's NHS Foundation Trust

Sheffield, S10 2TH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33761804 DERIVED

MeSH Terms

Conditions

Achondroplasia; Dwarfism; Bone Diseases; Musculoskeletal Diseases

Interventions

vosoritide

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Osteochondrodysplasias; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 18, 2020
• Study Start: October 10, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

AU (1); GB (2)