A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH) (ACH)
Primary Purpose
Achondroplasia
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BMN 111
Sponsored by
About this trial
This is an interventional treatment trial for Achondroplasia focused on measuring Achondroplasia, Dwarfism, Bone Diseases, Developmental, Bone Diseases
Eligibility Criteria
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.
Sites / Locations
- Children's Hospital & Research Center Oakland
- Harbor - UCLA Medical Center
- Ann and Robert H. Lurie Childrens Hospital of Chicago
- Johns Hopkins McKusick - Institute of Genetic Medicine
- Vanderbilt University
- Baylor College of Medicine
- Murdoch Children's Research Institute
- Institut Necker
- Guys & St. Thomas NHS Foundation Trust Evelina Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BMN 111 - Subcutaneous Injection
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Growth Velocity [Efficacy]
Annualized growth velocity (cm/yr)
Growth Parameters (Efficacy)
Height standard score (Z-score)
Body Proportions (Efficacy)
Upper-to-lower body segment ratio
Final Adult Height
Height at the age of 16 years for females and 18 years for males
Full Information
NCT ID
NCT02724228
First Posted
February 12, 2016
Last Updated
August 1, 2023
Sponsor
BioMarin Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT02724228
Brief Title
A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH)
Acronym
ACH
Official Title
A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children With Achondroplasia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 26, 2016 (Actual)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
February 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Achondroplasia
Keywords
Achondroplasia, Dwarfism, Bone Diseases, Developmental, Bone Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BMN 111 - Subcutaneous Injection
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
BMN 111
Other Intervention Name(s)
Modified recombinant human C-type natriuretic peptide, Vosoritide
Intervention Description
BMN 111 will be administered subcutaneously daily.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Number of study participants with treatment-emergent adverse events.
Number of study participants with treatment-emergent serious adverse events
Time Frame
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 Measure Information:
Title
Growth Velocity [Efficacy]
Description
Annualized growth velocity (cm/yr)
Time Frame
Until near final adult height is reached
Title
Growth Parameters (Efficacy)
Description
Height standard score (Z-score)
Time Frame
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
Title
Body Proportions (Efficacy)
Description
Upper-to-lower body segment ratio
Time Frame
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
Title
Final Adult Height
Description
Height at the age of 16 years for females and 18 years for males
Time Frame
Up to at least 16 years of age for females and 18 years of age for males
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, MD
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital & Research Center Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Harbor - UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
Ann and Robert H. Lurie Childrens Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins McKusick - Institute of Genetic Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2578
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Murdoch Children's Research Institute
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Institut Necker
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Guys & St. Thomas NHS Foundation Trust Evelina Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31269546
Citation
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.
Results Reference
derived
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A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH)
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