Clinical trial NCT01603095: A Multicenter, Multinational Clinical Assessment Study for Pediatric Patients With Achondroplasia
Official title: A Multicenter, Multinational Clinical Assessment Study for Pediatric Patients With Achondroplasia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Achondroplasia
Keywords: Achondroplasia
dwarfism
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2012-05-22
Enrollment: 363
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Approximately 500 patients will be enrolled. Patients from birth to \<= 17 years, inclusive, on the date of consent will be enrolled. Approximately equal numbers of boys and girls will be enrolled.

Brief summary: Multicenter, multinational study to collect consistent baseline growth measurements on pediatric patients with Achondroplasia being considered for subsequent enrollment in future studies sponsored by BioMarin. No study drug is administered.


Eligibility criteria: Inclusion Criteria:

* Parent(s) or guardian(s) willing and able to provide signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Also, willing and able to provide written assent (as needed) after the nature of the study has been explained and prior to performance of any research-related procedure.
* Aged 0 to \<= 17 years, inclusive, at study entry.
* Have ACH, documented by clinical diagnosis
* Are ambulatory and able to stand without assistance (not applicable for infants)
* Are willing and able to perform all study procedures as physically possible.

Exclusion Criteria:

* Have hypochondroplasia or short stature condition other than ACH (e.g., trisomy 21, pseudoachondroplasia)
* Have any of the following disorders:

  * Hypothyroidism
  * Insulin-requiring diabetes mellitus
  * Autoimmune inflammatory disease
  * Inflammatory bowel disease
  * Autonomic neuropathy
* Have an unstable clinical condition likely to lead to intervention during the course of the study, including progressive cervical medullary compression
* Growth plates have fused
* Have a history of any of the following:

  * Renal insufficiency
  * Anemia
* 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
  * Cerebrovascular disease, aortic insufficiency
  * Clinically significant atrial or ventricular arrhythmias
* Current treatment 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, drugs known to alter renal function that is expected to continue for the duration of the study
* Have been treated with growth hormone, insulin-like growth factor 1 (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
* 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 any condition that, in the view of the Investigator, places the patient at high risk of poor compliance with the visit schedule or of not completing the study.
* Concurrent disease or condition that, in the view of the Investigator, would interfere with study participation

Primary outcomes:
measure: Collection of consistent growth measurements
timeFrame: Assessed every 3 months for up to 84 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Wilmington
country: United States
facility: Nemours/Alfred I. duPont Hospital for Children
state: Delaware
city: Decatur
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Children's Hospital
state: Wisconsin
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Saitama
country: Japan
facility: Saitama Children's Medical Center
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Barcelona
country: Spain
facility: Institut Catala de Traumatologica I Medicina de l'Esport
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu Barcelona
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Istanbul
country: Turkey
facility: Acibadem University School of Medicine
city: London
country: United Kingdom
facility: Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's NHS Foundation Trust
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: Chan ML, Qi Y, Larimore K, Cherukuri A, Seid L, Jayaram K, Jeha G, Fisheleva E, Day J, Huntsman-Labed A, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Horton WA, Henshaw J. Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Clin Pharmacokinet. 2022 Feb;61(2):263-280. doi: 10.1007/s40262-021-01059-1. Epub 2021 Aug 25.
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.