Safety and Efficacy of Voxzogo for Growth Deficits in MPS IVA and VI

NCT05845749 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-37966
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II, single arm, open label study of vosoritide therapy provided subcutaneously at 15 ug/kg/day for 96 weeks to 6 patients with MPS IVA or VI. Prior to enrollment in the interventional arm of study, subjects will be followed for a minimum of 24 weeks to gather information on safety profiles and determine annualized growth velocity. The primary study endpoint is the determination of safety and tolerability of daily vosoritide treatment in MPS. Exploratory endpoints include changes in linear and segmental growth as well as biomarkers of growth and bone metabolism.

Conditions

MPS VI; MPS IVA

Keywords

Growth; Vosoritide; Children; Height; Voxzogo

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability: Incidence of adverse events while treated with vosoritide

  Incidence of treatment-emergent adverse events as assessed by the evaluation of vital signs, pulse oximetry, pulmonary function, ECG (cardiac arrhythmia), ECHO (doppler of aortic velocity for stenosis, aortic valve area, and qualitative assessment of aortic valve thickness), spinal X-rays (worsening scoliosis, lordosis or kyphosis), standing lower extremity X-rays (worsening of genu valgum), decrease in six-minute walk distance and linear and segmental growth for determination of excessive or disproportionate growth. All safety assessments will be performed at a minimum at the beginning of the intervention (Visit 1) and the end of the intervention (Visit 3) in patients with MPS IVA and VI

  48 weeks

Secondary Outcomes (1)

• Change in height velocity while treated with vosoritide

  120 weeks

Study Arms (1)

Vosoritide

OTHER

This is a single arm open label study of daily SQ dose of vosoritide

Drug: Vosoritide Injection [Voxzogo]

Interventions

Vosoritide Injection [Voxzogo] DRUG

Vosoritide will be given via a once daily subcutaneous injection at a dose of 15 ug/kg/day, at approximately the same time each day when feasible. Vosoritide will be supplied to the subject as 0.4 mg vial, 0.56 mg vial or 1.2 mg vials to be reconstituted with sterile water up to 0.8 mg/mL or 2 mg/mL concentrations for injection. The volume to be administered (injection volume) will be based on the subject's body weight and the concentration of vosoritide. All supplies will be provided to the subject for home based administration after training at the study site.

Also known as: Vosoritide, BMN111

Vosoritide

Eligibility Criteria

• Age: 5 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age \>= 5 years and \< 10 years
• Tanner stage 1
• Clinical Diagnosis of MPS IVA or VI
• Subjects will be stratified into 2 groups:
• MPS IVA (3 patients)
• MPS VI (3 patients)
• MPS Diagnosis Confirmed by either:
• Demonstration of 2 pathogenic or likely pathogen mutations (or homozygous for single mutation) and elevated GAG (either before or during ERT treatment), OR
• Demonstration of diagnostic enzyme deficiency, elevated GAG (either before or during ERT treatment), and a normal second sulfatase
• Currently receiving ERT \[elosulfase alfa (Vimizim®) or galsulfase (NAGLAZYME®)\] for minimum of 12 months prior to study entry
• HSCT greater than 3 years before entry
• Height Z-score \<-2.0 or less than 2 cm change in height velocity over the last 1 year
• Willing to consent to the study and comply with all study procedures and assessments
• Able to stand independently without hand support for minimum of one minute
• Guardians able to successfully administer investigational drug daily/SQ

You may not qualify if:

• ERT naïve
• Poor compliance with ERT (\<75% in 6 month period)
• Diagnosis with growth hormone deficiency (defined by IGF-1 SDS \<-1.0 according to age, gender and tanner stage)
• Hypothyroidism, untreated (TSH \>4.0 mU/L)
• Receiving or has received growth hormone therapy, IGF-1 therapy, anti-TNF alpha therapy, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium channel blockers, cardiac glycosides, systemic anticholinergic agents, any medication that may impair or enhance compensatory tachycardia, diuretics or other drugs known to alter renal or tubular function within the previous 6 months.
• Receiving or has previously received a GnRH analog (e.g. leuprolide acetate, histrelin)
• History of malignancy
• History of chronic inflammatory condition not related to MPS
• History of conditions/medical therapies that might affect the interpretation of growth results such as anemia, celiac disease, diabetes, inflammatory bowel disease, and cystic fibrosis
• QTC (Fridericia) \> 450 msec
• Malnutrition (BMI \<5th percentile)
• History of gene therapy
• Concurrent participation on an investigational drug trial
• Investigational drug washout minimum of 5 half-lives of the drug or 1 month whichever is longer
• Previous or current treatment with the investigational drug (vosoritide)

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis IV; Mucopolysaccharidosis VI

Interventions

vosoritide

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Ellen B Fung, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a 24 week natural history study followed by a 96 week open label single arm intervention with vosoritide

Study Record Dates

• First Submitted: April 14, 2023
• First Posted: May 6, 2023
• Study Start: September 25, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)