Open-label clinical trial with an open-label extension to investigate the safety of BMN 111 in infants and young children with achondroplasia

Phase 1

• Conditions: achondroplasia; MedDRA version: 20.0Level: LLTClassification code 10000452Term: AchondroplasiaSystem Organ Class: 100000004850; Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

• Registration Number: EUCTR2020-001055-40-GB
• Lead Sponsor: BioMarin Pharmaceutical Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-19
• Last Update Posted: 10 August 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

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.
2.Have ACH, documented by genetic testing.
3.Are willing and able to perform all study procedures as physically possible.
4.Age from 0 months to =12 months, at study entry (Day 1).
5.Parent(s) or caregiver(s) are willing to administer daily injections to the subject and complete the required training.
6.Have evidence of cervicomedullary compression (CMC) that may” require surgical intervention defined as:
oBaseline MRI assessment from central blinded evaluation showing at least one of the following findings:
-Narrowing of the foramen magnum with loss of cerebrospinal fluid space surrounding the cord.
-Narrowing of the foramen magnum with flattening of the cervical cord without T2 signal change.
oSupported by (but not required for eligibility) the following clinical findings:
Baseline physical examination
-Gross or fine motor developmental milestone delay compared to expected for ACH (eg, lifting head when lying on stomach).
•Abnormal reflex (eg, brisk reflex / abnormal clonus for age).
•Weakness (eg, opisthotonus).
-Baseline sleep study
•Sleep apnea with a primary central component (eg, not secondary to obstructive sleep apnea).

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
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

Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
1.Have hypochondroplasia or short-stature condition other than achondroplasia (eg, trisomy 21, pseudoachondroplasia, etc).
2.Have CMC that either does not require surgical intervention (for example foramen magnum narrowing with preservation of the cerebrospinal fluid space) or does require immediate surgical intervention (for example narrowing of the foramen magnum with cervical cord signal change).
3.Have any of the following:
oUntreated congenital hypothyroidism or maternal history of hyperthyroidism.
oInsulin-requiring neonatal diabetes mellitus.
oAutoimmune inflammatory disease.
oInflammatory bowel disease.
oAutonomic neuropathy.
4.Have a history of any of the following:
oRenal insufficiency.
oChronic anemia.
oBaseline systolic blood pressure below age and gender specified normal range or recurrent symptomatic hypotension (defined as episodes of low blood pressure generally accompanied by symptoms eg, pallor, cyanosis, irritability, poor feeding).
oCardiac or vascular disease, including the following:
?Cardiac dysfunction (abnormal echocardiogram determined to be clinically significant by Investigator and Medical Monitor) at Screening.
?Hypertrophic cardiomyopathy.
?Pulmonary hypertension.
?Clinically significant structural heart disease or valvular insufficiency (associated with symptoms or requiring intervention).
?Clinically significant cerebrovascular disease.
?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.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 that is expected to continue for the duration of the study.
7.Require any other investigational product prior to completion of the study period.
8.Have received another investigational product or investigational medical device within 30 days prior to Screening.
9.Have used any other investigational product or investigational medical device for the treatment of achondroplasia or short stature at any time.
10.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.
11.Have been treated with growth hormone, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time.
12.Have had regular long-term treatment ( > 1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma, or intranasal steroids, are acceptable) prior to Screening
13.Have ever had prior cervicomedullary decompression surgery.
14.Have had a fracture of the long bones or spine within 6 months prior to Screening.
15.Have aspartate aminotransferase, alanine aminotransferase, or total bilirubin > 2 × the upper limit of normal at Screening (except for subjects with a known history of Gilbert’s syndrome or transient indirect hyperbilirubinemia).
16.Have current malignancy, history of malig

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified