A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

Phase 3

Completed

• Conditions: Achondroplasia
• Interventions: Drug: BMN 111; Drug: Placebo

• Registration Number: NCT03197766
• Lead Sponsor: BioMarin Pharmaceutical

Brief Summary

The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for the treatment of children with Achondroplasia.

Detailed Description

This is a Phase 3 randomized, placebo-controlled, double-blind multicenter study with approximately 110 subjects, aged 5 to \< 18 years old. Subjects with documented Achondroplasia confirmed by genetic testing will have been enrolled in Study 111-901 for at least a 6-month period immediately before entering into the 111-301 study. Eligible subjects will be randomly assigned to one of two treatment groups: placebo or BMN 111 at 15 μg/kg. The route of administration is subcutaneous injection and the frequency is daily.

Study Timeline

• Study Start: 2016-12-12
• Study First Submitted: 2017-05-23
• Study First Submitted QC: 2017-06-21
• Study First Posted: 2017-06-23
• Primary Completion: 2019-10-30
• Study Completion: 2019-10-30
• Disposition First Submitted: 2020-05-13
• Disposition First Submitted QC: 2020-05-13
• Disposition First Posted: 2020-05-15
• Results First Submitted: 2021-12-15
• Status Verified: 2022-02
• Results First Submitted QC: 2022-02-04
• Last Update Submitted: 2022-02-04
• Results First Posted: 2022-03-02
• Last Update Posted: 2022-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active BMN 111	BMN 111	Daily subcutaneous injection of 15 micrograms per kilogram BMN111
Placebo	Placebo	Daily subcutaneous injection of placebo

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Annualized Growth Velocity (AGV) at Week 52	At Baseline and Week 52	AGV at a Post-baseline Visit is defined as \[(Height at Post-baseline Visit - Height at Baseline)/(Date of Post-baseline Visit - Date of Baseline Assessment)\] x 365.25; AGV at Baseline is defined as \[(Height at Baseline - last height measurement in Study 111-901 at least 6 months prior to Baseline)/(Date of Baseline Assessment - Date of last height measurement in Study 111-901 at least 6 months prior to Baseline)\] x 365.25

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Height Z-score at Week 52	At baseline and Week 52	Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention.; A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age.; A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age.; To conclude if the height Z score increases then this means the height deficit has decreased.
Change From Baseline in Upper to Lower Segment Body Ratio at Week 52	At baseline and Week 52	Evaluate change from baseline in mean upper:lower segment body ratio in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment	Up to Week 56	AEs with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included.; serious adverse event (SAE)

Trial Locations

Locations (24)

Ann and Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Emory University; 🇺🇸 Decatur, Georgia, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Saitama Children's Medical Center; 🇯🇵 Saitama, Japan

Children's Hospital & Research Center Oakland; 🇺🇸 Oakland, California, United States

Harbor - UCLA Medical Center; 🇺🇸 Torrance, California, United States

Alfred I. duPont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Missouri; 🇺🇸 Columbia, Missouri, United States

Medical College of Wisconsin, Children's Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

The Children's Hospital at Westmead; 🇦🇺 Westmead, New South Wales, Australia

Murdoch Children's Research Institute; 🇦🇺 Parkville, Victoria, Australia

Otto-von-Guericke Universitaet, Universitaetskinderklinik; 🇩🇪 Magdeburg, Germany

Osaka University Hospital; 🇯🇵 Osaka, Japan

Tokushima University Hospital; 🇯🇵 Tokushima, Japan

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Institut Catala de Traumatologica I Medicina de l'Esport; 🇪🇸 Barcelona, Spain

Hospital Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Sheffield Children's NHS Foundation Trust; 🇬🇧 Sheffield, United Kingdom

Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital; 🇬🇧 London, United Kingdom

Acibadem University School of Medicine; 🇹🇷 Istanbul, Turkey

Hospital Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States