AchondroplasiaPhase 2/3ASPENNCT07441876
Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia
A Phase 2/3 study testing BMN 333 and Vosoritide Injection [Voxzogo] in people with Achondroplasia, run by BioMarin Pharmaceutical at 28 sites in 9 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Achondroplasia
- What is being tested?
- BMN 333 and Vosoritide Injection [Voxzogo]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 28 sitesin 9 countries
- Study dates
- 20 Apr 2026to Sep 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
- Participants must have ACH (confirmed by documented genetic testing) and open epiphyses
- Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)
- Are ambulatory and able to stand without assistance
Who cannot join
- Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)
- 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.
- 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.
- Have had bone fractures of the long bones or spine within 6 months prior to screening.
- 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
- Have been treated with GH, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to treatment start
Trial locations and contacts
28 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
28 sites in 9 countries
United States9 sites, 9 recruiting
- Recruiting
Johns Hopkins Medicine
Baltimore, Maryland, 21205
Julie Hoover-Fong
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Carlos Prada
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Benjamin Cocanougher
- Recruiting
Texas Children's Hospital
Dallas, Texas, 75207
Nadia Merchant
- Recruiting
Texas Children Hospital, Baylor College of Medicine
Houston, Texas, 77030
Carlos Bacino
- Recruiting
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Hind Al-Saif
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
David Weber
- Recruiting
Consano Clinical Research, LLC
San Antonio, Texas, 78231
Daniel Katselnik
- Not yet recruiting
Nemours Children's Health
Wilmington, Delaware, 19803
Mahim Jain
United Kingdom6 sites, 6 recruiting
- Recruiting
University Hospitals Bristol NHS Foundation Trust - Bristol Royal Hospital for Children
Bristol
Toby Candler
- Recruiting
Queen Elizabeth University Hospital
Glasgow
Helen McDevitt
- Recruiting
Alder Hey Childrens NHS Foundation Trust
Liverpool
Sharanya Ramakrishnan
- Recruiting
Great Ormond Street Hospital
London
Moira Cheung
- Recruiting
St Thomas Hospital
London
Rhonda Akilapa
- Recruiting
University NHS Foundation Trust NIHR Wellcome Trust Clinical Research Facility
Manchester
Mars Skae
Japan3 sites, 3 recruiting
- Recruiting
Hokkaido University Hospital
Hokkaido
Shuntaro Morikawa
- Recruiting
Osaka City General Hospital
Osaka, 534-0021
Jun Mori
- Recruiting
National Center for Child Health and Development
Tokyo
Kenichi Kashimada
Canada2 sites, 2 recruiting
- Recruiting
Universite de Montreal - Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Philippe Campeau
- Recruiting
McGill University Health Centre
Québec, Monteral, H4A 3J1
Marie-Eve Robinson
Italy2 sites, 2 recruiting
- Not yet recruiting
Irccs Ospedale Gaslini Di Genova
Genova, 16147
Mohamed Maghnie
- Not yet recruiting
Fondazione IRCCS Ca Grande Ospedale Maggiore
Milan, 20122
Maria Francesca Bedeschi,
Romania2 sites, 2 recruiting
- Recruiting
Institutul National de Endocrinologie C.I.Parhon
Bucharest
Iuliana Gherlan
- Recruiting
Craiova Emergency Clinical County
Craiova, 200642
Ioana Streata
South Korea2 sites, 2 recruiting
- Recruiting
Seoul National University Hospital
Seoul
Jung Min Ko
- Recruiting
Pusan National University Yangsan Hospital
Yangsan, 50612
Chong-Kun Cheon
Australia1 site, 1 recruiting
- Recruiting
Murdoch Children's Research Institute
Parkville, Victoria, 3052
Ravi Savarirayan
Poland1 site, 1 recruiting
- Recruiting
Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu Klinika Pediatrii i Chorob Infekcyjnych
Wroclaw
Robert Shanislaw Smigiel
About this study
Official title: 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.
Read the 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
- Conditions
- Achondroplasia
- Being tested
- BMN 333, Vosoritide Injection [Voxzogo]
- Keywords
- Achondroplasia, ACH, Bone Diseases, Developmental Dwarfism, Bone Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Natriuretic Peptide, C-type, Osteochondrodysplasias, Physiological Effects of Drugs, Skeletal Dysplasias
- Medical subject headings
- Achondroplasia, Bone Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Osteochondrodysplasias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMN 333Drug
Administration: Weekly subcutaneous injection
Vosoritide Injection [Voxzogo]Drug
Administration: Daily subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Phase 2: Low Dose | Experimental | Participants will be randomized to receive different dose levels of BMN 333 Receives: Drug: BMN 333 |
| Phase 2: Medium Dose | Experimental | Participants will be randomized to receive different dose levels of BMN 333 Receives: Drug: BMN 333 |
| Phase 2: High Dose | Experimental | Participants will be randomized to receive different dose levels of BMN 333 Receives: Drug: BMN 333 |
| Phase 2: Vosoritide | Active comparator | weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide Receives: Drug: Vosoritide Injection [Voxzogo] |
| Phase 3: BMN 333 at selected dose after Phase 2 | Experimental | Not described Receives: Drug: BMN 333 |
| Phase 3: Vosoritide | Active comparator | weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide Receives: Drug: Vosoritide Injection [Voxzogo] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data]
Measured: 52 weeks
Phase 3: Annualized Growth Velocity (AGV) at Week 52
Measured: 52 weeks
Secondary outcomes (16)
Phase 2: AGV at Weeks 26 and 52
Measured: 26 and 52 weeks
Phase 2: Change from Baseline in standing height
Measured in centimeters
Measured: 26 and 52 weeks
Phase 2: Change from Baseline in height Z-score
Measured: 26 and 52 weeks
Phase 2: Change from Baseline in upper to lower body segment ratio
Measured: 26 and 52 weeks
Phase 2: Incidence of adverse events (AEs)
Measured: 52 weeks
Phase 2: Incidence of serious adverse events (SAEs)
Measured: 52 weeks
Phase 2: Incidence of events of interest (EOIs)
Measured: 52 weeks
Phase 2: Maximum concentration (Cmax) of BMN 333 in plasma
Measured: 52 weeks
Phase 2: Maximum concentration (Cmax) of released vosoritide in plasma
Measured: 52 weeks
Phase 2: Time to reach maximum concentration (Tmax) for BMN 333
Measured: 52 weeks
Phase 2: Time to reach maximum concentration (Tmax) for released vosoritide
Measured: 52 weeks
Phase 2: Lowest concentration (C trough) of BMN 333 in plasma
Measured: 52 weeks
Phase 2: Lowest concentration (C trough) of released vosoritide in plasma
Measured: 52 weeks
Phase 3: Change from Baseline in standing height
Measured in centimeters
Measured: 52 weeks
Phase 3: Change from Baseline in height Z-score
Measured: 52 weeks
Phase 3: Change from Baseline in upper to lower body segment ratio
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2026
- Study start20 Apr 2026
- Primary completionJun 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AchondroplasiaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, PhD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07441876
- Sponsor's protocol ID
- 333-301
- Acronym
- ASPEN
- Status last verified
- Sep 2026
- First submitted
- 11 Feb 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Operationally Seamless Phase 2/3 Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia
- ClinicalTrials.gov ID
- NCT07441876
- Acronym / sponsor ID
- ASPEN / 333-301
- Conditions
- Achondroplasia
- Keywords
- Achondroplasia, ACH, Bone Diseases, Developmental Dwarfism, Bone Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Natriuretic Peptide, C-type, Osteochondrodysplasias
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2026 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 2 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 2: Low Dose | Experimental | Drug: BMN 333Participants will be randomized to receive different dose levels of BMN 333 |
| Phase 2: Medium Dose | Experimental | Drug: BMN 333Participants will be randomized to receive different dose levels of BMN 333 |
| Phase 2: High Dose | Experimental | Drug: BMN 333Participants will be randomized to receive different dose levels of BMN 333 |
| Phase 2: Vosoritide | Active comparator | Drug: Vosoritide Injection [Voxzogo]weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide |
| Phase 3: BMN 333 at selected dose after Phase 2 | Experimental | Drug: BMN 333 |
| Phase 3: Vosoritide | Active comparator | Drug: Vosoritide Injection [Voxzogo]weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
- Participants must have ACH (confirmed by documented genetic testing) and open epiphyses
- Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)
- Are ambulatory and able to stand without assistance
Key exclusion criteria (6 listed)
- Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)
- 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.
- 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.
- Have had bone fractures of the long bones or spine within 6 months prior to screening.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMN 333Administration: Weekly subcutaneous injection | Drug | Phase 2: High Dose, Phase 2: Low Dose, Phase 2: Medium Dose, Phase 3: BMN 333 at selected dose after Phase 2 |
| Vosoritide Injection [Voxzogo]Administration: Daily subcutaneous injection | Drug | Phase 2: Vosoritide, Phase 3: Vosoritide |
Primary outcome
Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data]
Time frame: 52 weeks
Phase 3: Annualized Growth Velocity (AGV) at Week 52
Time frame: 52 weeks
16 secondary outcomes
Phase 2: AGV at Weeks 26 and 52
Time frame: 26 and 52 weeks
Phase 2: Change from Baseline in standing height
Time frame: 26 and 52 weeks
Phase 2: Change from Baseline in height Z-score
Time frame: 26 and 52 weeks
Phase 2: Change from Baseline in upper to lower body segment ratio
Time frame: 26 and 52 weeks
Phase 2: Incidence of adverse events (AEs)
Time frame: 52 weeks
Phase 2: Incidence of serious adverse events (SAEs)
Time frame: 52 weeks
Phase 2: Incidence of events of interest (EOIs)
Time frame: 52 weeks
Phase 2: Maximum concentration (Cmax) of BMN 333 in plasma
Time frame: 52 weeks
Phase 2: Maximum concentration (Cmax) of released vosoritide in plasma
Time frame: 52 weeks
Phase 2: Time to reach maximum concentration (Tmax) for BMN 333
Time frame: 52 weeks
Phase 2: Time to reach maximum concentration (Tmax) for released vosoritide
Time frame: 52 weeks
Phase 2: Lowest concentration (C trough) of BMN 333 in plasma
Time frame: 52 weeks
Phase 2: Lowest concentration (C trough) of released vosoritide in plasma
Time frame: 52 weeks
Phase 3: Change from Baseline in standing height
Time frame: 52 weeks
Phase 3: Change from Baseline in height Z-score
Time frame: 52 weeks
Phase 3: Change from Baseline in upper to lower body segment ratio
Time frame: 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Director, PhD study director
BioMarin Pharmaceutical
28 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing BMN 333 and Vosoritide Injection [Voxzogo] in people with Achondroplasia, run by BioMarin Pharmaceutical at 28 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, United Kingdom, Japan, Canada, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Trial Specialist (1-800-983-4587, medinfo@bmrn.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data] (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.