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A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia

Primary Purpose

Achondroplasia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BMN 111
Placebo
Sponsored by
BioMarin Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Achondroplasia focused on measuring Dwarfism, Bone Diseases, Bone Diseases, Developmental, ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases, Natriuretic Agents, Physiological Effect of Drugs, Skeletal Dysplasias, Genetic Diseases, Inborn, Osteochondrodysplasias

Eligibility Criteria

undefined - 59 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of ACH, confirmed by genetic testing
  • Age 0 to < 60 months at study entry (Day 1)
  • At least 6-month period of pretreatment growth assessment in Study 111-901 immediately before study entry (cohort 1 & 2) or at least 3 months of observation prior to treatment (cohort 3)

Exclusion Criteria:

  1. Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.)

  2. Have any of the following:

    • Hypothyroidism or hyperthyroidism
    • Insulin-requiring diabetes mellitus
    • Autoimmune inflammatory disease (including celiac disease, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma, etc.)
    • Inflammatory bowel disease
    • Autonomic neuropathy
  3. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F > 450 msec on screening ECG

  4. Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator and informed by the following assessments:

    • Physical exam (eg, neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins)
    • Polysomnography (eg, severe central sleep apnea)
    • MRI indicating presence of severe CMC or spinal cord damage
  5. Subject weight < 5.0 kg (cohort 1 & 2) or < 4.0 kg (cohort 3)
  6. Treatment with growth hormone within 6-months prior to screening or prolonged treatment (> 3 months) at any time
  7. Any history of spine or long-bone surgery or any bone-related surgery with chronic complications
  8. Any history of limb-lengthening surgery or planned limb-lengthening during the study
  9. Fracture of the long bones within 6 months prior to screening

Sites / Locations

  • Children's Hospital & Research Center Oakland
  • Harbor - UCLA Medical Center
  • Alfred I. duPont Hospital for Children
  • Emory University
  • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Cincinnati Children's Hospital Medical Center
  • Vanderbilt University Medical Center
  • Baylor College of Medicine
  • Medical College of Wisconsin, Children's Hospital
  • The Children's Hospital at Westmead
  • Murdoch Children's Research Institute
  • Osaka University Hospital
  • Saitama Children's Medical Center
  • Tokushima University Hospital
  • Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
  • Sheffield Children's NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active BMN111

Placebo

Arm Description

Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily

Daily subcutaneous injection of placebo

Outcomes

Primary Outcome Measures

Evaluate the effect of BMN 111 on change from baseline in length/height Z-scores
Evaluate change from baseline in length/height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks

Secondary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Evaluate the effect of BMN 111 on change from baseline in AGV
Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA)
Characterize maximum concentration (Cmax) of BMN 111 in plasma
Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)
Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
Characterize the elimination half-life of BMN 111 (t½)
Characterize the apparent clearance of drug
Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth
BMN 111 activity will be assessed by measuring bone and collagen metabolism
Evaluate the effect of BMN 111 on growth parameters and body proportions, including change from baseline in upper:lower segment body ratio
Evaluate the effect of BMN 111 on Sleep study scores by polysomnography

Full Information

First Posted
June 14, 2018
Last Updated
December 15, 2022
Sponsor
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT03583697
Brief Title
A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia
Official Title
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia, Age 0 to < 60 Months
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
May 23, 2018 (Actual)
Primary Completion Date
January 26, 2022 (Actual)
Study Completion Date
January 26, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Study 111-206 is a Phase 2 randomized, double-blind, placebo-controlled clinical trial of BMN 111 in infants and young children with a diagnosis of Achondroplasia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Achondroplasia
Keywords
Dwarfism, Bone Diseases, Bone Diseases, Developmental, ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases, Natriuretic Agents, Physiological Effect of Drugs, Skeletal Dysplasias, Genetic Diseases, Inborn, Osteochondrodysplasias

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active BMN111
Arm Type
Experimental
Arm Description
Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Daily subcutaneous injection of placebo
Intervention Type
Drug
Intervention Name(s)
BMN 111
Other Intervention Name(s)
Vosoritide, Modified recombinant human C-type natriuretic peptide
Intervention Description
Subcutaneous injection of 15 μg/kg of BMN 111 daily, Subject to adjustment per protocol
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneous injection of 15 μg/kg of placebo daily, Subject to adjustment per protocol
Primary Outcome Measure Information:
Title
Evaluate the effect of BMN 111 on change from baseline in length/height Z-scores
Description
Evaluate change from baseline in length/height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
Time Frame
One year
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame
One year
Title
Evaluate the effect of BMN 111 on change from baseline in AGV
Time Frame
One year
Title
Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA)
Time Frame
One year
Title
Characterize maximum concentration (Cmax) of BMN 111 in plasma
Time Frame
One year
Title
Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞)
Time Frame
One year
Title
Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
Time Frame
52 Weeks
Title
Characterize the elimination half-life of BMN 111 (t½)
Time Frame
52 weeks
Title
Characterize the apparent clearance of drug
Time Frame
52 weeks
Title
Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
Time Frame
52 weeks
Title
Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
Time Frame
52 weeks
Title
Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth
Time Frame
One year
Title
BMN 111 activity will be assessed by measuring bone and collagen metabolism
Time Frame
One year
Title
Evaluate the effect of BMN 111 on growth parameters and body proportions, including change from baseline in upper:lower segment body ratio
Time Frame
One year
Title
Evaluate the effect of BMN 111 on Sleep study scores by polysomnography
Time Frame
One year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of ACH, confirmed by genetic testing Age 0 to < 60 months at study entry (Day 1) At least 6-month period of pretreatment growth assessment in Study 111-901 immediately before study entry (cohort 1 & 2) or at least 3 months of observation prior to treatment (cohort 3) Exclusion Criteria: Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.) Have any of the following: Hypothyroidism or hyperthyroidism Insulin-requiring diabetes mellitus Autoimmune inflammatory disease (including celiac disease, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma, etc.) Inflammatory bowel disease Autonomic neuropathy Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F > 450 msec on screening ECG Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator and informed by the following assessments: Physical exam (eg, neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins) Polysomnography (eg, severe central sleep apnea) MRI indicating presence of severe CMC or spinal cord damage Subject weight < 5.0 kg (cohort 1 & 2) or < 4.0 kg (cohort 3) Treatment with growth hormone within 6-months prior to screening or prolonged treatment (> 3 months) at any time Any history of spine or long-bone surgery or any bone-related surgery with chronic complications Any history of limb-lengthening surgery or planned limb-lengthening during the study Fracture of the long bones within 6 months prior to screening
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
Alfred I. duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Emory University
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Ann and Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Vanderbilt University Medical Center
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
Medical College of Wisconsin, Children's Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
The Children's Hospital at Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Murdoch Children's Research Institute
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Osaka University Hospital
City
Osaka
Country
Japan
Facility Name
Saitama Children's Medical Center
City
Saitama
Country
Japan
Facility Name
Tokushima University Hospital
City
Tokushima
Country
Japan
Facility Name
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Sheffield Children's NHS Foundation Trust
City
Sheffield
ZIP/Postal Code
S10 2TH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://ghr.nlm.nih.gov/condition/achondroplasia
Description
NIH Genetics Home Reference related topics: Achondroplasia
URL
https://rarediseases.info.nih.gov/diseases/8173/achondroplasia
Description
Description NIH Genetic and Rare Diseases Information Center resources: Achondroplasia
URL
https://clinicaltrials.gov/ct2/info/fdalinks
Description
U.S. FDA Resources

Learn more about this trial

A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia

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