Achondroplasia
Conditions
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
Brief 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.
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
Interventions
DRUGBMN 333
Administration: Weekly subcutaneous injection
Administration: Daily subcutaneous injection
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 3: Annualized Growth Velocity (AGV) at Week 52 | 52 weeks |
| Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data] | 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Change from Baseline in standing height | 26 and 52 weeks | Measured in centimeters |
| 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 | 52 weeks | Measured in centimeters |
| 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 | — |
| Phase 2: AGV at Weeks 26 and 52 | 26 and 52 weeks | — |
Countries
Australia, United States
Contacts
CONTACTTrial Specialist
CONTACTStudy Manager
STUDY_DIRECTORMedical Director, PhD
BioMarin Pharmaceutical
Outcome results
None listed