Overview
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.
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
Eligibility
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
