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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03583697
Recruitment Status : Completed
First Posted : July 11, 2018
Last Update Posted : December 19, 2022
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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.

Condition or disease Intervention/treatment Phase
Achondroplasia Drug: BMN 111 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2018
Actual Primary Completion Date : January 26, 2022
Actual Study Completion Date : January 26, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Active BMN111
Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily
Drug: BMN 111
Subcutaneous injection of 15 μg/kg of BMN 111 daily, Subject to adjustment per protocol
Other Names:
  • Vosoritide
  • Modified recombinant human C-type natriuretic peptide

Placebo Comparator: Placebo
Daily subcutaneous injection of placebo
Drug: Placebo
Subcutaneous injection of 15 μg/kg of placebo daily, Subject to adjustment per protocol

Primary Outcome Measures :
  1. Evaluate the effect of BMN 111 on change from baseline in length/height Z-scores [ Time Frame: One year ]
    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 :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: One year ]
  2. Evaluate the effect of BMN 111 on change from baseline in AGV [ Time Frame: One year ]
  3. Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA) [ Time Frame: One year ]
  4. Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: One year ]
  5. Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: One year ]
  6. Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [ Time Frame: 52 Weeks ]
  7. Characterize the elimination half-life of BMN 111 (t½) [ Time Frame: 52 weeks ]
  8. Characterize the apparent clearance of drug [ Time Frame: 52 weeks ]
  9. Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: 52 weeks ]
  10. Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: 52 weeks ]
  11. Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth [ Time Frame: One year ]
  12. BMN 111 activity will be assessed by measuring bone and collagen metabolism [ Time Frame: One year ]
  13. 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 ]
  14. Evaluate the effect of BMN 111 on Sleep study scores by polysomnography [ Time Frame: One year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 59 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03583697

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United States, California
Children's Hospital & Research Center Oakland
Oakland, California, United States, 94609
Harbor - UCLA Medical Center
Torrance, California, United States, 90509
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2578
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin, Children's Hospital
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
The Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Murdoch Children's Research Institute
Parkville, Victoria, Australia, 3052
Osaka University Hospital
Osaka, Japan
Saitama Children's Medical Center
Saitama, Japan
Tokushima University Hospital
Tokushima, Japan
United Kingdom
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
London, United Kingdom, SE1 9RT
Sheffield Children's NHS Foundation Trust
Sheffield, United Kingdom, S10 2TH
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Medical Director, MD BioMarin Pharmaceutical
Additional Information:
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03583697    
Other Study ID Numbers: 111-206
2016-003826-18 ( EudraCT Number )
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: December 19, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioMarin Pharmaceutical:
Bone Diseases
Bone Diseases, Developmental
Natriuretic Peptide, C-Type
Musculoskeletal Diseases
Natriuretic Agents
Physiological Effect of Drugs
Skeletal Dysplasias
Genetic Diseases, Inborn
Additional relevant MeSH terms:
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Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Natriuretic Peptide, C-Type
Natriuretic Agents
Physiological Effects of Drugs