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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03583697




Registration number
NCT03583697
Ethics application status
Date submitted
14/06/2018
Date registered
11/07/2018
Date last updated
24/05/2019

Titles & IDs
Public title
A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia
Scientific 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
Secondary ID [1] 0 0
2016-003826-18
Secondary ID [2] 0 0
111-206
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Achondroplasia 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BMN 111
Treatment: Drugs - Placebo

Experimental: Active BMN111 - Daily subcutaneous injection of 15 micrograms per kilogram BMN111 daily

Placebo Comparator: Placebo - Daily subcutaneous injection of placebo


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

Treatment: Drugs: Placebo
Subcutaneous injection of 15 µg/kg of placebo daily, Subject to adjustment per protocol

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
One year
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Timepoint [1] 0 0
One year
Secondary outcome [2] 0 0
Evaluate the effect of BMN 111 on change from baseline in AGV
Timepoint [2] 0 0
One year
Secondary outcome [3] 0 0
Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA)
Timepoint [3] 0 0
One year
Secondary outcome [4] 0 0
Characterize maximum concentration (Cmax) of BMN 111 in plasma
Timepoint [4] 0 0
One year
Secondary outcome [5] 0 0
Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8)
Timepoint [5] 0 0
One year
Secondary outcome [6] 0 0
Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t)
Timepoint [6] 0 0
52 Weeks
Secondary outcome [7] 0 0
Characterize the elimination half-life of BMN 111 (t½)
Timepoint [7] 0 0
52 weeks
Secondary outcome [8] 0 0
Characterize the apparent clearance of drug
Timepoint [8] 0 0
52 weeks
Secondary outcome [9] 0 0
Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
Timepoint [9] 0 0
52 weeks
Secondary outcome [10] 0 0
Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
Timepoint [10] 0 0
52 weeks
Secondary outcome [11] 0 0
Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth
Timepoint [11] 0 0
One year
Secondary outcome [12] 0 0
BMN 111 activity will be assessed by measuring bone and collagen metabolism
Timepoint [12] 0 0
One year
Secondary outcome [13] 0 0
Evaluate the effect of BMN 111 on growth parameters and body proportions, including change from baseline in upper:lower segment body ratio
Timepoint [13] 0 0
One year
Secondary outcome [14] 0 0
Evaluate the effect of BMN 111 on Sleep study scores by polysomnography
Timepoint [14] 0 0
One year

Eligibility
Key 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)
Minimum age
No limit
Maximum age
59 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
United Kingdom
State/province [9] 0 0
London
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BioMarin Pharmaceutical
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03583697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director, MD
Address 0 0
BioMarin Pharmaceutical
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03583697