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

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

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.

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

• Drug BMN 333
  Administration: Weekly subcutaneous injection
• Drug Vosoritide Injection [Voxzogo]
  Administration: Daily subcutaneous injection

Primary outcome measures

• 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]

Secondary outcome measures (12)

• 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 9 centers

• UCSF Benioff Children's Hospital Oakland — Oakland
• Nemours Children's Health — Wilmington
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Johns Hopkins Medicine — Baltimore
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Children's Hospital of Philadelphia — Philadelphia
• University of Texas Southwestern Medical Center — Dallas
• Texas Children Hospital, Baylor College of Medicine — Houston
• … and 1 more center

Romania · 2 centers

• Institutul National de Endocrinologie C.I.Parhon — Bucharest
• Craiova Emergency Clinical County — Craiova

South Korea · 2 centers

• Seoul National University Hospital — Seoul
• Pusan National University Yangsan Hospital — Yangsan

Australia · 1 center

• Murdoch Children's Research Institute — Parkville

Canada · 1 center

• Universite de Montreal - Centre Hospitalier Universitaire Sainte-Justine — Montreal

Italy · 1 center

• Irccs Ospedale Gaslini Di Genova — Genova

Japan · 1 center

• Osaka City General Hospital — Osaka

Poland · 1 center

• Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu Klinika Pediatrii — Wroclaw

United Kingdom · 1 center

• University Hospitals Bristol NHS Foundation Trust - Bristol Royal Hospital for Children — Bristol

Identifiers

NCT: NCT07441876 · 333-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗