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

Sponsor

BioMarin Pharmaceutical (Industry)

Overall Status

Completed

CT.gov ID

NCT03583697

Collaborator

(none)

Enrollment

Locations

Arms

44.2

Actual Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Achondroplasia	Drug: BMN 111 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 23, 2018

Actual Primary Completion Date :

Jan 26, 2022

Actual Study Completion Date :

Jan 26, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active BMN111 Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily	Drug: BMN 111 Subcutaneous injection of 15 μg/kg of BMN 111 daily, Subject to adjustment per protocol Other Names: Vosoritide Modified recombinant human C-type natriuretic peptide
Placebo Comparator: Placebo Daily subcutaneous injection of placebo	Drug: Placebo Subcutaneous injection of 15 μg/kg of placebo daily, Subject to adjustment per protocol

Arm

Intervention/Treatment

Experimental: Active BMN111

Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily

Drug: BMN 111

Subcutaneous injection of 15 μg/kg of BMN 111 daily, Subject to adjustment per protocol

Other Names:

Vosoritide

Modified recombinant human C-type natriuretic peptide

Placebo Comparator: Placebo

Daily subcutaneous injection of placebo

Drug: Placebo

Subcutaneous injection of 15 μg/kg of placebo daily, Subject to adjustment per protocol

Outcome Measures

Primary Outcome Measures

Evaluate the effect of BMN 111 on change from baseline in length/height Z-scores [One year]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 59 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

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

Subject weight < 5.0 kg (cohort 1 & 2) or < 4.0 kg (cohort 3)
Treatment with growth hormone within 6-months prior to screening or prolonged treatment (> 3 months) at any time
Any history of spine or long-bone surgery or any bone-related surgery with chronic complications
Any history of limb-lengthening surgery or planned limb-lengthening during the study
Fracture of the long bones within 6 months prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital & Research Center Oakland	Oakland	California	United States	94609
2	Harbor - UCLA Medical Center	Torrance	California	United States	90509
3	Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
4	Emory University	Decatur	Georgia	United States	30033
5	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
6	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
7	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-2578
8	Baylor College of Medicine	Houston	Texas	United States	77030
9	Medical College of Wisconsin, Children's Hospital	Milwaukee	Wisconsin	United States	53226
10	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
11	Murdoch Children's Research Institute	Parkville	Victoria	Australia	3052
12	Osaka University Hospital	Osaka		Japan
13	Saitama Children's Medical Center	Saitama		Japan
14	Tokushima University Hospital	Tokushima		Japan
15	Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital	London		United Kingdom	SE1 9RT
16	Sheffield Children's NHS Foundation Trust	Sheffield		United Kingdom	S10 2TH