Clinical trial • Phase II/III • Rare Disease

BMN 333 for Achondroplasia

Phase II/III trial of BMN 333 for Achondroplasia.

Overview

Trial Therapeutic Area
Rare Disease
Trial Disease
Achondroplasia
Trial Stage
Phase II/III
Drug Modality
Peptide/protein/enzyme
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
19-02-2026
First CTIS Authorization Date
05-05-2026

Trial design

Randomised, open-label, vosoritide (voxzogo) — subcutaneous (sc) once daily, weight‑band dosing (protocol references voxzogo 0.56 mg and voxzogo 1.2 mg presentations).-controlled, adaptive Phase II/III trial across 7 sites in Italy, Romania, Poland.

Randomised
Yes
Open Label
Yes
Comparator
Vosoritide (Voxzogo) — subcutaneous (SC) once daily, weight‑band dosing (protocol references Voxzogo 0.56 mg and Voxzogo 1.2 mg presentations).
Adaptive
True, interim analysis planned after all Phase 2 participants complete 26 weeks or discontinue earlier; unblinded review of efficacy, safety and available PK data to select Phase 3 dose and decide whether to proceed to Phase 3 (operationally seamless Phase 2/3 design).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
160
Trial Duration For Participant
427

Stratification factors

  • Sex
  • Age group (≥5 years vs <5 years) - Phase 2
  • Tanner stage - Phase 3

Eligibility

Recruits 160 paediatric patients.

Pregnancy Exclusion
3.Females ≥ 10 years old or who have begun menses must have a negative pregnancy test at the Screening visit and be willing to have additional pregnancy tests during the study.
Vulnerable Population
Participants are children (paediatric population) aged from ≥2 to <11 years (Phase 2) and ≥2 to <18 years (Phase 3). Vulnerable-population procedures are in place: parent/guardian consent and age-appropriate assent forms are provided (documents include assent forms for younger children and older children/adolescents). Multiple site-specific ICF and assent documents are provided (examples in Italian, Polish, Romanian). Caregivers are required to be willing to administer injections and complete required training.

Inclusion criteria

  • {"criterion_text":"- 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.\n- 2.Participants must have ACH (confirmed by documented genetic testing) and open epiphyses assessed using left hand postero-anterior (PA) X-rays, by the Greulich and Pyle method (Greulich 1971) as per standard of care.\n- 3.Females ≥ 10 years old or who have begun menses must have a negative pregnancy test at the Screening visit and be willing to have additional pregnancy tests during the study.\n- 4.Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)\n- 5.Have a body weight ≥ 8.0 kg at the Screening visit\n- 6.Are ambulatory and able to stand without assistance\n- 7.Caregivers are willing to administer injections to the participants and willing to complete the required training."}

Exclusion criteria

  • {"criterion_text":"- 1.Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency).\n- 2.Have any of the following disorders:Hypothyroidism or hyperthyroidism (unless treated) ,Diabetes mellitus (unless considered well-controlled), Autoimmune inflammatory disease, Autoimmune inflammatory disease ,Autonomic neuropathy.\n- 3.Have history of: Renal insufficiency, Cardiac or vascular disease, unstable clinical condition , significant hip pathology."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Phase 2: Predicted AGV at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data])","definition_or_measurement_approach":"Predicted annualized growth velocity (AGV) at Week 52 estimated based on observed AGV at Weeks 26, 39 and 52 (cumulative data available for interim assessments)."}
  • {"endpoint_text":"- Phase 3: AGV at Week 52","definition_or_measurement_approach":"Annualized growth velocity (AGV) measured at Week 52."}

Secondary endpoints

  • {"endpoint_text":"- Phase 2: 1.AGV at Weeks 26 and 52 2.Change from Baseline in standing height, height Z-score and in upper to lower body segment ratio at Weeks 26 and 52 3.Incidence of AEs, SAEs, and EOIsa; physical examinations; vital signs; ECG findings; imaging results (X-ray and DXA); clinical laboratory tests.","definition_or_measurement_approach":"AGV measured at Weeks 26 and 52; standing height, height Z-score and upper/lower body segment ratio changes from baseline at Weeks 26 and 52; safety measured by incidence of adverse events, serious adverse events and events of special interest, plus physical exams, vital signs, ECG, imaging (X-ray and DXA) and clinical laboratory tests."}
  • {"endpoint_text":"- Phase 3: • Change from Baseline in standing height, height Z-score, upper to lower body segment ratio at Week 52","definition_or_measurement_approach":"Change from baseline in standing height, height Z-score and upper to lower body segment ratio measured at Week 52."}

Recruitment

Planned Sample Size
160
Recruitment Window Months
37
Consent Approach
Informed consent is obtained from parents/legal guardians. Age-appropriate assent is obtained from children using specific assent documents (examples: Assent 6-11, Assent 12-17, Young Child Assent, Older Child Assent). Site-specific subject information and informed consent forms and assent forms are provided in multiple languages (document list includes Italian, Polish and Romanian versions). Parent/guardian ICFs and optional research consent forms are included for each country/site.

Methods

  • Site-based recruitment at participating hospitals/clinical sites in the listed countries (Italy, Romania, Poland) — recruitment through the trial sites named in Part II submissions.
  • Provision of patient recruitment materials managed by ICON Clinical Research Limited (duty listed: 'Patient recruitement Materials').
  • Patient reimbursement handled by Scout Clinical (duty listed: 'Patient reimbursement').

Geography

Total Number Of Sites
7
Total Number Of Participants
25

Italy

Earliest CTIS Part Ii Submission Date
10-04-2026
Latest Decision Or Authorization Date
05-05-2026
Processing Time Days
25
Number Of Sites
3
Number Of Participants
15

Sites

Site Name
IRCCS Istituto Giannina Gaslini
Department Name
Pediatric Clinic - Clinical Service in Pediatric Endocrinology, Diabetes and Metabolism
Contact Person Name
Mohamad Maghnie
Contact Person Email
mohamadmaghnie@gaslini.org
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Pediatrics
Contact Person Name
Roberta Onesimo
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Maternal and Childhood Area
Contact Person Name
Maria Francesca Bedeschi

Romania

Earliest CTIS Part Ii Submission Date
14-04-2026
Latest Decision Or Authorization Date
05-05-2026
Processing Time Days
21
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
National Institute Of Endocrinology C.I. Parhon
Department Name
Endocrinology
Contact Person Name
Iuliana Gherlan
Contact Person Email
contact@parhon.ro
Site Name
Spitalul Clinic Judetean De Urgenta Craiova
Department Name
Genetics
Contact Person Name
Ioana Streata
Contact Person Email
info@scjuc.ro

Poland

Earliest CTIS Part Ii Submission Date
13-04-2026
Latest Decision Or Authorization Date
05-05-2026
Processing Time Days
22
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Pediatrii, Endokrynologii, Diabetologii i Chorób Metabolicznych
Contact Person Name
Robert Śmigiel
Contact Person Email
robert.smigiel@umw.edu.pl
Site Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 Im.Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego W Katowicach
Department Name
Poradnia Endokrynologii Dziecięcej
Contact Person Name
Agnieszka Zachurzok
Contact Person Email
azachurzok@sum.edu.pl

Sponsor

Primary sponsor

Full Name
Biomarin Pharmaceutical Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Medpace Belgium
Name
Icon Clinical Research Limited
Responsibilities
Site and contract negotiation, Medical Imaging, In-home health, language services, Patient recruitement Materials.
Name
Imperial Clinical Research Services International Ltd.
Responsibilities
printing
Name
Medpace Singapore Pte Ltd
Name
Medpace Reference Laboratories LLC

Third parties

  • {"country":"Belgium","full_name":"Medpace Belgium","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Sysnav","duties_or_roles":"Digital Health Technologies (DHT)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"long term storage","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"Antropometric Measurement training","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Woodley Equipment Company Limited","duties_or_roles":"Anthropometric Equipment","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Quipment","duties_or_roles":"Equipmental Rental","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Imperial Clinical Research Services International Ltd.","duties_or_roles":"printing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Singapore","full_name":"Medpace Singapore Pte Ltd","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Site and contract negotiation, Medical Imaging, In-home health, language services, Patient recruitement Materials.","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BMN 333
Active Substance
BMN 333
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
prodAuthStatus: 1 (not marketing authorised / development product)
Dose Levels
Three weekly dose levels (Dose A, Dose B, Dose C) described in Phase 2; specific numeric doses not stated in CTIS data
Frequency
Once weekly (protocol: BMN 333 once weekly in Phase 2 and selected once-weekly dose in Phase 3)
Dose Escalation Increase
Dose A, Dose B, Dose C (specific increases not stated in CTIS data)
Investigational Product Name
Voxzogo 0.56 mg powder and solvent for solution for injection
Active Substance
VOSORITIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
Authorised (marketingAuthNumber: EU/1/21/1577/002)
Orphan Designation
Yes
Dose Levels
Weight-band daily dosing as per protocol (specific weight-band doses not provided in CTIS data); product strength 0.56 mg referenced
Frequency
Once daily (weight-band dosing)
Maximum Dose
0.40 mg (maxDailyDoseAmount field in CTIS record)
Investigational Product Name
Voxzogo 1.2 mg powder and solvent for solution for injection
Active Substance
VOSORITIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
Authorised (marketingAuthNumber: EU/1/21/1577/003)
Orphan Designation
Yes
Dose Levels
Weight-band daily dosing as per protocol (specific weight-band doses not provided in CTIS data); product strength 1.2 mg referenced
Frequency
Once daily (weight-band dosing)
Maximum Dose
0.80 mg (maxDailyDoseAmount field in CTIS record)

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