A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia

Achondroplasia Clinical Trial

Official title:

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia, Age 0 to < 60 Months

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03583697
• Other study ID #: 111-206
• Secondary ID: 2016-003826-18
• Status: Completed
• Phase: Phase 2
• Start date: May 23, 2018
• Est. completion date: January 26, 2022

Study information

• Verified date: February 2022
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study 111-206 is a Phase 2 randomized, double-blind, placebo-controlled clinical trial of BMN 111 in infants and young children with a diagnosis of Achondroplasia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: January 26, 2022
• Est. primary completion date: January 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 59 Months

Eligibility

Inclusion Criteria:

• Diagnosis of ACH, confirmed by genetic testing
• Age 0 to < 60 months at study entry (Day 1)
• At least 6-month period of pretreatment growth assessment in Study 111-901 immediately before study entry (cohort 1 & 2) or at least 3 months of observation prior to treatment (cohort 3)

Exclusion Criteria:

1. Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.)

2. 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

3. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F > 450 msec on screening ECG

4. Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator and

informed by the following assessments:

• Physical exam (eg, neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins)
• Polysomnography (eg, severe central sleep apnea)
• MRI indicating presence of severe CMC or spinal cord damage

5. Subject weight < 5.0 kg (cohort 1 & 2) or < 4.0 kg (cohort 3)

6. Treatment with growth hormone within 6-months prior to screening or prolonged treatment (> 3 months) at any time

7. Any history of spine or long-bone surgery or any bone-related surgery with chronic complications

8. Any history of limb-lengthening surgery or planned limb-lengthening during the study

9. Fracture of the long bones within 6 months prior to screening

Related Conditions & MeSH terms

• Achondroplasia

Intervention

Drug:
• BMN 111
Subcutaneous injection of 15 µg/kg of BMN 111 daily, Subject to adjustment per protocol
• Placebo
Subcutaneous injection of 15 µg/kg of placebo daily, Subject to adjustment per protocol

Locations

Country	Name	City	State
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Japan	Osaka University Hospital	Osaka
Japan	Saitama Children's Medical Center	Saitama
Japan	Tokushima University Hospital	Tokushima
United Kingdom	Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital	London
United Kingdom	Sheffield Children's NHS Foundation Trust	Sheffield
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Emory University	Decatur	Georgia
United States	Baylor College of Medicine	Houston	Texas
United States	Medical College of Wisconsin, Children's Hospital	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital & Research Center Oakland	Oakland	California
United States	Harbor - UCLA Medical Center	Torrance	California
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Australia,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the effect of BMN 111 on change from baseline in length/height Z-scores	Evaluate change from baseline in length/height Z-score in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks	One year
Secondary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		One year
Secondary	Evaluate the effect of BMN 111 on change from baseline in AGV		One year
Secondary	Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA)		One year
Secondary	Characterize maximum concentration (Cmax) of BMN 111 in plasma		One year
Secondary	Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8)		One year
Secondary	Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)		52 Weeks
Secondary	Characterize the elimination half-life of BMN 111 (t½)		52 weeks
Secondary	Characterize the apparent clearance of drug		52 weeks
Secondary	Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)		52 weeks
Secondary	Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)		52 weeks
Secondary	Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth		One year
Secondary	BMN 111 activity will be assessed by measuring bone and collagen metabolism		One year
Secondary	Evaluate the effect of BMN 111 on growth parameters and body proportions, including change from baseline in upper:lower segment body ratio		One year
Secondary	Evaluate the effect of BMN 111 on Sleep study scores by polysomnography		One year

External Links

•   Description NIH Genetic and Rare Diseases Information Center resources: Achondroplasia
•   NIH Genetics Home Reference related topics: Achondroplasia
•   U.S. FDA Resources