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

NCT03197766 | Completed Phase 3 Results DMC

• 2 other identifiers: 111-3012015-003836-11
• Study Type: interventional
• Target: 121
• Locations: 7 countries
• Sites: 24

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.

Conditions

Achondroplasia

Keywords

Achondroplasia; Dwarfism; Bone Diseases; Bone Diseases, Developmental; ACH; Natriuretic Peptide, C-Type; Musculoskeletal Diseases; Natriuretic Agents; Physiological Effects of Drugs; Skeletal Dysplasias; Genetic Diseases, Inborn; Osteochondrodysplasias

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Annualized Growth Velocity (AGV) at 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

  At Baseline and Week 52

Secondary Outcomes (3)

• Change From Baseline in Height Z-score at Week 52

  At baseline and Week 52

• Change From Baseline in Upper to Lower Segment Body Ratio at Week 52

  At baseline and Week 52

• Summary of Subjects Experiencing Adverse Events (AEs) During Treatment

  Up to Week 56

Study Arms (2)

Active BMN 111

EXPERIMENTAL

Daily subcutaneous injection of 15 micrograms per kilogram BMN111

Drug: BMN 111

Placebo

PLACEBO COMPARATOR

Daily subcutaneous injection of placebo

Drug: Placebo

Interventions

BMN 111 DRUG

Subcutaneous injection of 15 μg/kg of BMN 111 daily

Also known as: Vosoritide, Modified recombinant human C-type natriuretic peptide

Active BMN 111

Placebo DRUG

Subcutaneous injection of 15 μg/kg of placebo daily

Placebo

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Parent(s) or guardian(s) consent
• to \< 18 years old
• ACH, documented and confirmed by genetic testing
• At least a 6-month period of pretreatment growth assessment in Study 111-901 before study entry
• If sexually active, willing to use a highly effective method of contraception
• Ambulatory and able to stand without assistance

You may not qualify if:

• Hypochondroplasia or short stature condition other than ACH
• Have any of the following:
• Hypothyroidism or hyperthyroidism
• Insulin-requiring diabetes mellitus
• Autoimmune inflammatory disease
• Inflammatory bowel disease
• Autonomic neuropathy
• History of any of the following:
• Renal insufficiency defined as serum creatinine \> 2 mg/dL
• Chronic anemia
• Baseline systolic blood pressure (BP) \< 70 millimeters of mercury (mm Hg) or recurrent symptomatic hypotension (defined as episodes of low BP generally accompanied by symptoms ie, dizziness, fainting) or recurrent symptomatic orthostatic hypotension
• Cardiac or vascular disease
• Have a clinically significant finding or arrhythmia on screening electrocardiogram (ECG) that indicates abnormal cardiac function or conduction or Fridericias corrected QTc-F \> 450 msec
• Have an unstable condition likely to require surgical intervention during the study (including progressive cervical medullary compression or severe untreated sleep apnea)
• Decreased growth velocity (\< 1.5 cm/yr) over a period of 6 months or evidence of growth plate closure (proximal tibia, distal femur)

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (24)

Children's Hospital & Research Center Oakland

Oakland, California, 94609, United States

Location

Harbor - UCLA Medical Center

Torrance, California, 90509, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Emory University

Decatur, Georgia, 30033, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Missouri

Columbia, Missouri, 65201, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin, Children's Hospital

Milwaukee, Wisconsin, 53226, United States

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Otto-von-Guericke Universitaet, Universitaetskinderklinik

Magdeburg, 39120, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Osaka University Hospital

Osaka, Japan

Location

Saitama Children's Medical Center

Saitama, Japan

Location

Tokushima University Hospital

Tokushima, Japan

Location

Institut Catala de Traumatologica I Medicina de l'Esport

Barcelona, 08028, Spain

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Acibadem University School of Medicine

Istanbul, 34752, Turkey (Türkiye)

Location

Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital

London, SE1 9RT, United Kingdom

Location

Sheffield Children's NHS Foundation Trust

Sheffield, S10 2TH, United Kingdom

Location

Related Publications (4)

• Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Palm K, Prada CE, Kubota T, Arundel P, Kotani Y, Leiva-Gea A, Bober MB, Hecht JT, Legare JM, Lawrinson S, Low A, Sabir I, Huntsman-Labed A, Day JRS. Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study. Med. 2025 May 9;6(5):100566. doi: 10.1016/j.medj.2024.11.019. Epub 2024 Dec 30.

  PMID: 39740666 DERIVED

• Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Mohnike K, Prada CE, Kubota T, Arundel P, Leiva-Gea A, Rowell R, Low A, Sabir I, Huntsman-Labed A, Day J. Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life. Genet Med. 2024 Dec;26(12):101274. doi: 10.1016/j.gim.2024.101274. Epub 2024 Sep 18.

  PMID: 39305160 DERIVED

• Qi Y, Chan ML, Mould DR, Larimore K, Fisheleva E, Cherukuri A, Day J, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Bober MB, Henshaw J. Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model. Clin Pharmacokinet. 2024 May;63(5):707-719. doi: 10.1007/s40262-024-01371-6. Epub 2024 Apr 23.

  PMID: 38649657 DERIVED

• Chan ML, Qi Y, Larimore K, Cherukuri A, Seid L, Jayaram K, Jeha G, Fisheleva E, Day J, Huntsman-Labed A, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Horton WA, Henshaw J. Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Clin Pharmacokinet. 2022 Feb;61(2):263-280. doi: 10.1007/s40262-021-01059-1. Epub 2021 Aug 25.

  PMID: 34431071 DERIVED

Related Links

• NIH Genetics Home Reference related topics: Achondroplasia
• NIH Genetic and Rare Diseases Information Center resources: Achondroplasia
• U.S. FDA Resources

MeSH Terms

Conditions

Achondroplasia; Dwarfism; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Genetic Diseases, Inborn; Osteochondrodysplasias

Interventions

vosoritide

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Results Point of Contact

• Title: Alice Huntsman Labed
• Organization: BioMarin Pharmaceutical Inc.

alice.huntsmanlabed@bmrn.com

+44 207 4203392

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: June 23, 2017
• Study Start: December 12, 2016
• Primary Completion: October 30, 2019
• Study Completion: October 30, 2019
• Last Updated: March 2, 2022
• Results First Posted: March 2, 2022

Record last verified: 2022-02

Locations

ES (3); AU (2); DE (2); GB (2); US (11); TU (1); JP (3)