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

Purpose

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.

Condition

  • Achondroplasia

Eligibility

Eligible Ages
Between 2 Years and 17 Years
Eligible Sex
All
Accepts 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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

UCSF Benioff Children's Hospital Oakland
Oakland, California 94609
Contact:
Hind Al-Saif

Texas Children Hospital, Baylor College of Medicine
Houston, Texas 77030
Contact:
Carlos Bacino

Consano Clinical Research, LLC
San Antonio, Texas 78231
Contact:
Daniel Katselnik

More Details

Status
Recruiting
Sponsor
BioMarin Pharmaceutical

Study Contact

Trial Specialist
1-800-983-4587
medinfo@bmrn.com

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