A Phase 2 Study to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children with Achondroplasia
- Conditions
- AchondroplasiaMedDRA version: 20.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 100000004850Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]
- Registration Number
- EUCTR2016-003826-18-GB
- Lead Sponsor
- BioMarin Pharmaceutical Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 70
1. Diagnosis of ACH, confirmed by genetic testing. If subjects had previous genetic testing, subjects must have a lab report from a certified laboratory with the study specific mutation documented.
2. Age 0 to < 60 months, at study entry (Day 1)
3. Cohort 1 and 2 subjects must have at least a 6-month period of pre-treatment growth assessment in Study 111-901 immediately before screening and have one documented measurement of height/body length a minimum of 6 months (+/- 10 days) prior to the screening visit for 111-206. Cohort 3 subjects must have a minimum of 3 months of observation prior to treatment. This observational period can be obtained either (1) via prior enrolment in Study 111-901 or (2) via enrolment in this Study 111-206 for a minimum of 3 months of non-treatment observation prior to commencement of treatment.
4. Parent(s) or guardian(s) (and the subjects themselves, if required by local regulations or ethics committee) 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
5. Willing and able to perform all study procedures as physically possible
6. Parent(s) or caregiver(s) are willing to administer daily injections to the subjects and complete the required training.
Inclusion Criteria for Cohort 3 Observation Period
Individuals eligible to participate in this study must meet all of the following criteria:
1.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 (if applicable) after the nature of the study has been explained and prior to performance of any research-related procedure.
2.Birth to = 3 months of age at study entry.
3.Have ACH, documented by genetic testing
4.Are willing and able to perform all study procedures as physically possible
After completing observation period subjects must fulfil the general eligibility criteria prior to receiving treatment with study drug.
Are the trial subjects under 18? yes
Number of subjects for this age range: 70
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
1. Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.)
2. Subject weighs < 5.0 kg (Cohort 1 and 2) or < 4.0 kg (Cohort 3; treatment phase)
3. 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
4. Have a history of any of the following:
- Renal insufficiency defined as serum creatinine > 2 mg/dL
- Chronic anemia or Hgb < 10.0 g/dL (based on screening clinical laboratory testing)
- Baseline systolic blood pressure (BP) below age and gender specified normal range or recurrent symptomatic hypotension (defined as episodes of low BP generally accompanied by symptoms e.g., dizziness, fainting) or recurrent symptomatic orthostatic hypotension
- Cardiac or vascular disease, including the following
o Cardiac dysfunction (abnormal echocardiogram determined to be
clinically significant by PI and medical monitor) at Screening Visit
o Hypertrophic cardiomyopathy
o Pulmonary hypertension
o Congenital heart disease with ongoing cardiac dysfunction
o Cerebrovascular disease
o Aortic insufficiency or other clinically significant valvular dysfunction
o Clinically significant atrial or ventricular arrhythmias
5. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F > 450 msec on screening ECG
6. Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator and informed on the following assessments:
- Physical exam (e.g., neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins)
- Polysomnography (e.g., severe central sleep apnea)
- MRI indicating presence of severe CMC or spinal cord damage
7. Have an unstable medical condition likely to require surgical intervention in the next 6 months, or planned spine or long-bone surgery (i.e., surgery involving significant disruption of bone cortex) during the study period
8. Have documented uncorrected Vitamin D deficiency: 25(OH)D = 15 ng/mL (37.5 nmol/L)
9. Require any other investigational product prior to completion of the study period
10. Have received another investigational product or investigational medical device within 30 days prior to the Screening visit
11. Have used any other investigational product or investigational medical device for the treatment of achondroplasia or short stature at any time
12. Require current chronic therapy with antihypertensive medication or any medication that, in the investigator’s judgment, may compromise the safety or ability of the subject to participate in this clinical study
13. Have been treated with growth hormone, insulin-like grow
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method