A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia (ACH)

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
First received: April 18, 2013
Last updated: September 2, 2015
Last verified: September 2015
This is a Phase 2, open-label, sequential cohort dose-escalation study of BMN 111 in children with achondroplasia. The primary objective is to assess the safety and tolerability of daily BMN 111 administered to children with achondroplasia.

Condition Intervention Phase
Drug: BMN 111
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Sequential Cohort Dose-escalation Study of BMN 111 in Children With Achondroplasia

Resource links provided by NLM:

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Safety Measures [ Time Frame: 6 months and approximately 24 months ] [ Designated as safety issue: Yes ]
    Safety evaluations by incidence of adverse events, serious adverse events, laboratory test results (urinalysis, chemistry, hematology), clinically significant changes in vital signs, physical examination, ECG and ECHO results, imaging, hip monitoring and anti-BMN 111 immunogenicity assessments.

Secondary Outcome Measures:
  • Efficacy measure [ Time Frame: 6 months and approximately 24 months ] [ Designated as safety issue: No ]
    Efficacy will be assessed by change from baseline in height growth velocity (annualized to cm/yr), absolute growth, subject growth compared with ACH and non-ACH standardized pediatric growth curves, and change in body proportions. These will be assessed by anthropometric measurements and measurement ratios.

Estimated Enrollment: 46
Study Start Date: January 2014
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMN 111 - Subcutaneous Injection

111-202 is an open-label sequential cohort dose-escalation study. BMN 111 will be administered as a morning dose in one of the following daily dosing regimens:

• Cohort 1: 2.5 microgram/kg, Cohort 2: 7.5 microgram/kg, Cohort 3: 15.0 microgram/kg, Cohort 4: 30.0 microgram/kg and Cohort 5: up to 60.0 microgram/kg

Drug: BMN 111
BMN 111 will be administered daily for 24 months in an open-label sequential dose adjustment fashion.
Other Names:
  • Modified recombinant human C-type natriuretic peptide
  • Vosoritide


Ages Eligible for Study:   5 Years to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Parent(s) or guardian(s) are willing and able to provide written, signed informed consent
  • 5 to 14 years old at study end
  • ACH, documented by clinical grounds, confirmed by genetic testing
  • At least 6-month of pretreatment growth assessment in Study 111-901 before study entry, and one standing height at least 6 months prior to screening for 111-202
  • Negative pregnancy test at the Screening Visit for females ≥ 10 years old.
  • If sexually active, willing to use a highly effective method of contraception while participating in the study
  • Ambulatory, able to stand without assistance
  • Willing and able to perform all study procedures as physically possible
  • Parents/caregivers willing to administer daily injections to the subjects

Additional inclusion Criteria Optional, Open-label Extension Phase:

  • Appropriate written informed consent

Exclusion Criteria:

  • 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
    • Recent acute illness associated with volume dehydration not completely resolved prior to the first dose of study drug
  • Unstable condition requiring surgical intervention during the study
  • Growth plates have fused
  • Have a history of any of the following:

    • Renal insufficiency, defined as creatinine > 2 mg/dl
    • Anemia
    • Baseline systolic BP < 75 mm Hg or recurrent symptomatic hypotension or recurrent symptomatic hypotension, recurrent symptomatic orthostatic hypotension
    • Cardiac or vascular disease, including the following:

      • Cardiac dysfunction (abnormal echocardiogram [ECHO] including left ventricle [LV] mass) at Screening Visit
      • Hypertrophic cardiomyopathy
      • Pulmonary Hypertension
      • Congenital heart disease with ongoing cardiac dysfunction
      • Cerebrovascular disease
      • Aortic insufficiency
      • Clinically significant atrial or ventricular arrhythmias
  • Have an ECG showing any of the following:

    • Right or left atrial enlargement or ventricular hypertrophy
    • PR (period of time from the beginning of atrial depolarization until the beginning of ventricular depolarization) interval > 200 msec
    • QRS (The Q, R, and S heart waves that are measured on an electrocardiogram) interval > 110 msec
    • Corrected QTc-F (Measure of the corrected time between the start of the Q wave and end of the T wave in the heart's electrical cycle) > 450 msec
    • Second- or third-degree atrioventricular block
  • Documented Vitamin D deficiency
  • Require any investigational agent prior to completion of study period
  • Have received another investigational product or investigational medical device within 30 days before the Screening visit
  • Use of any other investigational product or investigational medical device for the treatment of ACH or short stature
  • Current chronic therapy with antihypertensive medications, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function
  • Treatment with growth hormone, IGF-1 (Insulin-like growth factor), or anabolic steroids in the previous 6 months or long-term treatment (> 3 months) at any time
  • Long-term treatment (> 1 month) with oral corticosteroids
  • Concomitant medication that prolongs the QT/QTc-F interval within 14 days or 5 half-lives, whichever is longer, before the Screening visit
  • Pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study
  • Limb-lengthening or bone-related surgery < 18 months prior to study enrollment
  • Had a fracture of the long bones or spine within 6 months prior to screening (except for fracture of digits or toes)
  • AST (Aspartate Transaminase) or ALT (Alanine Transaminase) at least 3x upper limit of normal (ULN) or total bilirubin at least 2x ULN
  • Evidence of severe sleep apnea requiring surgery or new initiation of CPAP (Continuous positive airway pressure).
  • History of malignancy and chemotherapy/radiation or currently under work-up for suspected malignancy
  • Known hypersensitivity to BMN 111 or its excipients
  • 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 would interfere with study participation or safety
  • Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant as determined by the PI.
  • Have a history of hip surgery or severe hip dysplasia
  • Have a history of clinically significant hip injury in the 30 days prior to screening.
  • History of slipped capital femoral epiphysis or avascular necrosis of the femoral head.
  • Are unable to lie flat when in prone position

Additional Exclusion Criteria for Optional, Open-label Extension Phase:

  • Use of restricted therapies during the initial 6 months of the study
  • Permanently discontinued BMN 111 during the initial 6 months of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02055157

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, Illinois
Ann and Robert H. Lurie Childrens Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins McKusick - Institute of Genetic Medicine
Baltimore, Maryland, United States, 21287
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232-2578
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Australia, Victoria
Murdoch Children's Research Institute
Parkville, Victoria, Australia, 3052
Institut Necker
Paris, France, 75015
United Kingdom
Guys & St. Thomas NHS Foundation Trust Evelina Hospital
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
BioMarin Pharmaceutical
Study Director: Medical Director, MD BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02055157     History of Changes
Other Study ID Numbers: 111-202, 2013-004137-32
Study First Received: April 18, 2013
Last Updated: September 2, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Human Research Ethics Committee
France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes

Keywords provided by BioMarin Pharmaceutical:
Bone Diseases, Developmental
Bone Diseases

Additional relevant MeSH terms:
Bone Diseases
Bone Diseases, Developmental
Genetic Diseases, Inborn
Musculoskeletal Diseases
Natriuretic Peptide, C-Type
Cardiovascular Agents
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 30, 2015