A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH) (ACH)

A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children With Achondroplasia

This is a Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children with Achondroplasia. The primary objective is to evaluate the long-term safety and tolerability of daily SC injections of BMN 111 in children with ACH who have completed two years of treatment in the 111-202 study.

Study Overview

• Status: Active, not recruiting
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: BMN 111

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• France
  • Paris, France, 75015
    • Institut Necker
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guys & St. Thomas NHS Foundation Trust Evelina Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland
    • Torrance, California, United States, 90509
      • Harbor - UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Childrens Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins McKusick - Institute of Genetic Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2578
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have completed 24 months of BMN 111 treatment in Study 111-202.
• Parent(s) or guardian(s) are willing and able to provide written, signed informed consent. Subjects under the age of majority are willing and able to provide written assent (if required). Subjects who reach the age of majority in their country will be asked to provide their own written consent upon reaching the legal age of majority.
• If sexually active, willing to use a highly effective method of contraception while participating in the study.
• Females >= 10 years old or who have started menses must have a negative pregnancy test at baseline and be willing to have additional pregnancy tests during the study
• Willing and able to perform all study procedures as physically possible
• Parents/caregivers willing to administer daily injections to the subjects and complete the required training.

Exclusion Criteria:

• Requires any investigational agent prior to completion of study period.
• Have a condition or circumstance that, in the view of the Investigator, places the subject at high risk for poor treatment compliance or for not completing the study.
• Concurrent disease or condition that, in the view of the Investigator, would interfere with study participation or safety evaluations for any reason.
• Permanently discontinued BMN 111 during the 111-202 study.
• Subject is pregnant at Baseline visit or planning to become pregnant (self or partner) at any time during the study.
• Current chronic therapy with restricted medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMN 111 - Subcutaneous Injection; 111-205 is an open-label, extension study. Subjects receive the same stable dose of BMN 111 received upon completion of the 111-202 study, initially up to 30 μg/kg. BMN 111 will be administered by weight-band dosing regimen.	Drug: BMN 111; BMN 111 will be administered subcutaneously daily.; Other Names: Vosoritide; Modified recombinant human C-type natriuretic peptide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Number of study participants with treatment-emergent adverse events.; Number of study participants with treatment-emergent serious adverse events	Until near final adult height is reached, and up to at least 16 years of age for females and 18 years of age for males, whichever occurs later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth Velocity [Efficacy]	Annualized growth velocity (cm/yr)	Until near final adult height is reached
Growth Parameters (Efficacy)	Height standard score (Z-score)	Until near final adult height is reached, and up to at least 16 years of age for females and 18 years of age for males, whichever occurs later
Body Proportions (Efficacy)	Upper-to-lower body segment ratio	Until near final adult height is reached, and up to at least 16 years of age for females and 18 years of age for males, whichever occurs later
Final Adult Height	Height at the age of 16 years for females and 18 years for males	Up to at least 16 years of age for females and 18 years of age for males

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Publications and helpful links

General Publications

• Savarirayan R, Irving M, Bacino CA, Bostwick B, Charrow J, Cormier-Daire V, Le Quan Sang KH, Dickson P, Harmatz P, Phillips J, Owen N, Cherukuri A, Jayaram K, Jeha GS, Larimore K, Chan ML, Huntsman Labed A, Day J, Hoover-Fong J. C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. N Engl J Med. 2019 Jul 4;381(1):25-35. doi: 10.1056/NEJMoa1813446. Epub 2019 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: March 25, 2016
• First Posted (Estimated): March 31, 2016

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Bone Diseases; Bone Diseases, Developmental; Achondroplasia; Dwarfism
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, C-Type
• Other Study ID Numbers: 111-205; 2015-004004-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO