Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia (ASPEN)

A Multicenter, Randomized, Operationally Seamless Phase 2/3 Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia

This is a multicenter, multinational, randomized, active-controlled, operationally seamless Phase 2/3 study of BMN 333 in treatment-naïve pediatric participants with achondroplasia (ACH). The study consists of a Phase 2 part and a Phase 3 part.

Study Overview

• Status: Recruiting
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: BMN 333; Drug: Vosoritide Injection [Voxzogo]

Detailed Description

The main purpose of this study is to evaluate the effects of BMN 333 on growth compared with vosoritide in participants with achondroplasia who have not received any growth-promoting treatments. The study includes 2 parts: the Phase 2 part will select the optimal BMN 333 dose to be used in Phase 3 and determine study continuation into Phase 3; the Phase 3 part will compare the effects of the selected dose of BMN 333 with vosoritide. Study details for either Phase 2 or Phase 3 include the following:

• Study duration: up to 61 weeks (from screening to Safety Follow-up visit)
• Treatment duration: 52 weeks. Treatment frequency: BMN 333, once weekly; vosoritide, once daily

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Trial Specialist; Phone Number: 1-800-983-4587; Email: medinfo@bmrn.com
• Study Contact Backup: Name: Study Manager; Phone Number: 1-800-983-4587; Email: Medinfo@bmrn.com

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Murdoch Children's Research Institute
      • Contact: Ravi Savarirayan
• Italy
  • Genova, Italy, 16147
    • Not yet recruiting
    • Irccs Ospedale Gaslini Di Genova
    • Contact: Mohamed Maghnie
• Romania
  • Craiova, Romania, 200642
    • Not yet recruiting
    • Craiova Emergency Clinical County
    • Contact: Ioana Streata
• South Korea
  • Seoul, South Korea
    • Not yet recruiting
    • Seoul National University Hospital
    • Contact: Jung Min Ko
• United Kingdom
  • Bristol, United Kingdom
    • Not yet recruiting
    • University Hospitals Bristol NHS Foundation Trust - Bristol Royal Hospital for Children
    • Contact: Toby Candler
• United States
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Benioff Children's Hospital Oakland
      • Contact: Hind Al-Saif
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Contact: Carlos Prada
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Not yet recruiting
      • Johns Hopkins Medicine Julie
      • Contact: Julie Hoover-Fong
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children Hospital, Baylor College of Medicine, Houston TX
      • Contact: Carlos Bacino
    • San Antonio, Texas, United States, 78231
      • Recruiting
      • Consano Clinical Research, LLC
      • Contact: Daniel Katselnik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be aged ≥ 2 to < 11 years (Phase 2) or ≥ 2 to < 18 years (Phase 3), at the time of signing the informed consent
2. Participants must have ACH (confirmed by documented genetic testing) and open epiphyses
3. Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)
4. Are ambulatory and able to stand without assistance

Exclusion Criteria:

1. Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)
2. Have any of the following disorders: Hypothyroidism or hyperthyroidism, unless treated with evidence of normalized thyroid-stimulating hormone (TSH) levels, diabetes mellitus, unless considered well-controlled, autoimmune inflammatory disease, inflammatory bowel disease, autonomic neuropathy, anemia defined as hemoglobin < 10 g/dL, vitamin D deficiency, significant hip pathology.
3. Have history of any renal insufficiency or cardiac/ cardiovascular disease that places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension.
4. Have had bone fractures of the long bones or spine within 6 months prior to screening.
5. Have used vosoritide, any other approved product (except GH, as detailed below), investigational product, or investigational medical device for the treatment of ACH or short stature at any time
6. Have been treated with GH, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to treatment start

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2: Low Dose; Participants will be randomized to receive different dose levels of BMN 333	Drug: BMN 333; Administration: Weekly subcutaneous injection
Experimental: Phase 2: Medium Dose; Participants will be randomized to receive different dose levels of BMN 333	Drug: BMN 333; Administration: Weekly subcutaneous injection
Experimental: Phase 2: High Dose; Participants will be randomized to receive different dose levels of BMN 333	Drug: BMN 333; Administration: Weekly subcutaneous injection
Active Comparator: Phase 2: Vosoritide; weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide	Drug: Vosoritide Injection [Voxzogo]; Administration: Daily subcutaneous injection
Experimental: Phase 3: BMN 333 at selected dose after Phase 2	Drug: BMN 333; Administration: Weekly subcutaneous injection
Active Comparator: Phase 3: Vosoritide; weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide	Drug: Vosoritide Injection [Voxzogo]; Administration: Daily subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data]	52 weeks
Phase 3: Annualized Growth Velocity (AGV) at Week 52	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: AGV at Weeks 26 and 52		26 and 52 weeks
Phase 2: Change from Baseline in standing height	Measured in centimeters	26 and 52 weeks
Phase 2: Change from Baseline in height Z-score		26 and 52 weeks
Phase 2: Change from Baseline in upper to lower body segment ratio		26 and 52 weeks
Phase 2: Incidence of adverse events (AEs)		52 weeks
Phase 2: Incidence of serious adverse events (SAEs)		52 weeks
Phase 2: Incidence of events of interest (EOIs)		52 weeks
Phase 2: Maximum concentration (Cmax) of BMN 333 in plasma		52 weeks
Phase 2: Maximum concentration (Cmax) of released vosoritide in plasma		52 weeks
Phase 2: Time to reach maximum concentration (Tmax) for BMN 333		52 weeks
Phase 2: Time to reach maximum concentration (Tmax) for released vosoritide		52 weeks
Phase 2: Lowest concentration (C trough) of BMN 333 in plasma		52 weeks
Phase 2: Lowest concentration (C trough) of released vosoritide in plasma		52 weeks
Phase 3: Change from Baseline in standing height	Measured in centimeters	52 weeks
Phase 3: Change from Baseline in height Z-score		52 weeks
Phase 3: Change from Baseline in upper to lower body segment ratio		52 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Physiological Effects of Drugs; Bone Diseases; Achondroplasia; ACH; Skeletal Dysplasias; Bone Diseases, Developmental Dwarfism; Natriuretic Peptide, C-type
• Additional Relevant MeSH Terms: Bone Diseases, Developmental; Dwarfism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Achondroplasia; Osteochondrodysplasias; vosoritide
• Other Study ID Numbers: 333-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified individual participant data that underlie reported results (including text, tables, figures, and appendices) will be made available together with the research protocol and data dictionaries, for non-commercial, academic purposes. Additional supporting documents may be available upon request. Investigators will be able to request access to these data and supporting documents via a data sharing portal beginning 6 months and ending 2 years after publication. Data associated with any ongoing development program will be made available within six (6) months after approval of relevant product. Requests must include a research proposal clarifying how the data will be used, including proposed analysis methodology. Research proposals will be evaluated relative to publicly available criteria available at www.BioMarin.com/patients/publication-data-request/ to determine if access will be given, contingent upon execution of a data access agreement with BioMarin.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No