A Study to Evaluate Safety, Tolerability, and Efficacy of BMN 111 in Children with Achondroplasia

Phase 1

Conditions: achondroplasia
MedDRA version: 18.0Level: LLTClassification code 10000452Term: AchondroplasiaSystem Organ Class: 100000004850
Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

Registration Number: EUCTR2013-004137-32-FR

Lead Sponsor: BioMarin Pharmaceutical Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

1.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 by local regulations or the IRB/EC) after the nature of the study has been explained and prior to performance of any research-related procedure.
2.Are 5 to 14 years old, inclusive, at study entry
3.Have ACH, documented by clinical grounds and confirmed by genetic testing
4.Have at least a 6-month period of pretreatment growth assessment in Study 111 901 immediately before study entry, and has one documented standing height at least 6 months (+/- 10 days) prior to the screening visit for 111-202
5.Females = 10 years old must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
6.If sexually active, willing to use a highly effective method of contraception while participating in the study
7.Are ambulatory and able to stand without assistance
8.Are willing and able to perform all study procedures as physically possible
9.Parents or caregivers are willing to administer daily injections to the subjects

Additional Inclusion Criteria for Optional, Open-label Extension Phase:
1.Appropriate written informed consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Have hypochondroplasia or short stature condition other than ACH (eg, trisomy 21, pseudoachondroplasia)
2.Have any of the following:
a.Hypothyroidism or hyperthyroidism
b.Insulin-requiring diabetes mellitus
c.Autoimmune inflammatory disease (including celiac disease, lupus (SLE), juvenile dermatomyositis, scleroderma, and others)
d.Inflammatory bowel disease
e.Autonomic neuropathy
f.Recent acute illness associated with volume depletion (e.g., nausea, vomiting, diarrhea) that has not completely resolved prior to the first dose of the study drug
3.Have an unstable condition likely to require surgical intervention during the study (including progressive cervical medullary compression)
4.Growth plates have fused
5.Have a history of any of the following:
a.Renal insufficiency, defined as creatinine > 2 mg/dl
b.Anemia
c.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
d.Cardiac or vascular disease, including the following:
i.Cardiac dysfunction (abnormal ECHO including abnormal LV mass) at Screening Visit
ii.Hypertrophic cardiomyopathy
iii.Pulmonary hypertension
iv.Congenital heart disease with ongoing cardiac dysfunction
v.Cerebrovascular disease
vi.Aortic insufficiency
vii.Clinically significant atrial or ventricular arrhythmias
6.Have the following confirmed ECG findings:
a.Right or left atrial enlargement or ventricular hypertrophy
b.PR interval > 200 msec
c.QRS interval > 110 msec
d.Corrected QTc > 450 msec
e.Second- or third-degree atrioventricular block
7.Documented Vitamin D deficiency (i.e., concentration of 25-hydroxy-vitamin D in the blood serum occurs at 12 ng/mL or less)
8.Require any investigational agent prior to completion of study period
9.Have received another investigational product or investigational medical device within 30 days before the Screening visit
10.Have used any other investigational product or investigational medical device for the treatment of ACH or short stature at any time
11.Current chronic therapy 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, diuretics, or other drugs known to alter renal or tubular function
12.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
13.Have had regular long-term treatment (> 1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma, or intranasal steroids, are acceptable)
14.Concomitant medication that prolongs the QT/QTc interval within 14 days or 5 half lives, whichever is longer, before the Screening visit
15.Pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study.
16.Have had limb-lengthening or bone-related surgery or expected to have limb-lengthening or bone-related surgery during the study period. Subjects with previous limb-lengthening or bone-related surgery may enroll if surgery occurred at least 18 months prior to the study and healing is complete without sequelae.
17.Have had a fracture of the long bones or spine within 6 months prior to screening (except for fracture of d