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Trial record 4 of 7 for:    "Achondroplasia"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by BioMarin Pharmaceutical
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT02055157
First received: April 18, 2013
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

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
Achondroplasia
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: Approximately 6 months. Following completion of study (Month 6), a safety follow up visit will be conducted (Month 7). ] [ Designated as safety issue: Yes ]
    Safety evaluations by indicence of adverse events, serious adverse events, laboratory test results (urinaysis, chemistry, hematology), clinically significant changes in vital signs, physical examination, ECG and ECHO results, imaging, and anti-BMN 111 immunogenicity assessments.


Secondary Outcome Measures:
  • Efficacy measure [ Time Frame: Approximately 6 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: 24
Study Start Date: January 2014
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (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, and Cohort 3: 15.0 microgram/kg.

Drug: BMN 111
BMN 111 will be administered daily for 6 months in an open-label sequential dose escalation fashion.
Other Name: Modified recombinant human C-type natriuretic peptide

  Eligibility

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

Inclusion Criteria:

  • Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Also, subjects under the age of 18 are willing and able to provide written assent (if required) after the nature of the study has been explained and prior to performance of any research-related procedure.
  • Are 5 to 14 years old, inclusive
  • Have ACH, documented by clinical grounds and confirmed by genetic testing
  • Have at least a 6-month period of pretreatment growth assessment in Study 111-901 immediately before study entry
  • Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study
  • If sexually active, willing to use an acceptable method of contraception while participating in the study
  • Are ambulatory and able to stand without assistance
  • Are willing and able to perform all study procedures as physically possible
  • Parents or caregivers are willing to administer daily injections to the subjects

Exclusion Criteria:

  • Have hypochondroplasia or short stature condition other than ACH (eg, trisomy 21, pseudoachondroplasia)
  • Have any of the following:

    • Hypothyroidism
    • Insulin-requiring diabetes mellitus
    • Autoimmune inflammatory disease
    • Inflammatory bowel disease
    • Autonomic neuropathy
    • Acute illness associated with volume dehydration (eg, nausea, vomiting, diarrhea)
  • Have an unstable condition likely to require surgical intervention during the study (including progressive cervical medullary compression)
  • Growth plates have fused
  • Have a history of any of the following:

    • Renal insufficiency
    • Anemia
    • Baseline systolic BP < 75 mm Hg or recurrent symptomatic hypotension (defined as episodes of low BP generally accompanied by symptoms i.e., dizziness, fainting) or 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
    • 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 interval > 200 msec
    • QRS interval > 110 msec
    • Corrected QTc > 440 msec
    • Second- or third-degree atrioventricular block
  • Demonstrate vitamin D deficiency (i.e., concentration of 25-hydroxy-vitamin D in the blood serum occurs at 12 ng/mL or less)
  • 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
  • Pregnant or breastfeeding at the Screenng Visit or planning to become pregnant (self or partner) at any time during the study
  • Current treatment with antihypertensive medications, 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, drugs known to alter renal function
  • Have been treated with growth hormone, IGF-1, or anabolic steroids in the previous 6 months or long-term treatment (> 3 months) at any time
  • Have had regular long-term treatment (> 1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable)
  • Concomitant medication that prolongs the QT/QTc interval within 14 days or 5 half-lives, whichever is longer, before the Screening visit
  • Unwilling to temporarily discontinue CPAP use for 2 days prior to Screening visit if applicable
  • Have used any other investigational product or investigational medical device for the treatment of ACH or short stature
  • Have had bone-related surgery or expected to have bone-related surgery during the study period. Subjects with previous limb-lengthening surgery may enroll if surgery occurred at least 18 months prior to the study and healing is complete without sequelae
  • Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at least 3x upper limit of normal (ULN) or total bilirubin at least 2x ULN
  • Have known hypersensitivity to BMN 111 or its excipients
  • Has 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, or would predispose the subject to hypotension (such as recent gastroenteritis or dehydration for any reason)
  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

Contacts
Contact: Robin McMahon, MPH rmcmahon@bmrn.com

Locations
United States, California
Not yet recruiting
Oakland, California, United States, 94609
United States, Illinois
Recruiting
Chicago, Illinois, United States, 60611
United States, Maryland
Not yet recruiting
Baltimore, Maryland, United States, 21287
United States, Tennessee
Not yet recruiting
Nashville, Tennessee, United States, 37232-2578
United States, Texas
Not yet recruiting
Houston, Texas, United States, 77030
Australia, Victoria
Not yet recruiting
Parkville, Victoria, Australia, 3052
France
Not yet recruiting
Paris, France, 75015
United Kingdom
Not yet recruiting
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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: February 3, 2014
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:
Achondroplasia
Dwarfism
Bone Diseases, Developmental
Bone Diseases

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

ClinicalTrials.gov processed this record on November 19, 2014