Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03989947




Registration number
NCT03989947
Ethics application status
Date submitted
22/05/2019
Date registered
18/06/2019
Date last updated
11/12/2023

Titles & IDs
Public title
An Extension Study to Evaluate Safety and Efficacy of BMN 111 in Children With Achondroplasia
Scientific title
A Phase 2 Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia
Secondary ID [1] 0 0
111-208
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 - Active BMN 111: Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.

Experimental: Active BMN 111 - Once daily subcutaneous injections of recommended dose of BMN 111 based on weight-band dosing.


Treatment: Drugs: Active BMN 111: Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.
Modified recombinant human C-type natriuretic peptide (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 incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Timepoint [1] 0 0
"Through study completion, an average of 5 years"
Primary outcome [2] 0 0
Evaluate change in height/length z-score in children with ACH treated with BMN 111
Timepoint [2] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [1] 0 0
Evaluate the change from baseline of mean annualized growth velocity (AGV)
Timepoint [1] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [2] 0 0
Characterize maximum concentration (Cmax) of BMN 111 in plasma
Timepoint [2] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [3] 0 0
Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8)
Timepoint [3] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [4] 0 0
Characterize the elimination half-life of BMN 111 (t½)
Timepoint [4] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [5] 0 0
Characterize the apparent clearance of drug
Timepoint [5] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [6] 0 0
Characterize the apparent volume of distribution based upon the terminal phase (Vz/F)
Timepoint [6] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [7] 0 0
Characterize the amount of time BMN 111 is present at maximum concentration (Tmax)
Timepoint [7] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [8] 0 0
Evaluate the change from baseline on body proportion ratios of the extremities
Timepoint [8] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [9] 0 0
Effect of BMN 111 on bone morphology and quality by XRay
Timepoint [9] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [10] 0 0
The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry
Timepoint [10] 0 0
"Through study completion, an average of 5 years"
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
"Through study completion, an average of 5 years"
Secondary outcome [12] 0 0
BMN 111 activity will be assessed by measuring bone and collagen metabolism
Timepoint [12] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [13] 0 0
Describe the incidence of surgical and medical interventions related to achondroplasia
Timepoint [13] 0 0
"Through study completion, an average of 5 years"
Secondary outcome [14] 0 0
Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old.
Timepoint [14] 0 0
"Through study completion, an average of 1 year"
Secondary outcome [15] 0 0
Evaluate the effect of BMN 111 on skull and brain morphology, including foramen magnum, ventricular and brain parenchymal dimensions by MRI in patients up to 3 years old.
Timepoint [15] 0 0
"Through study completion, an average of 1 year"

Eligibility
Key inclusion criteria
1. Must have completed Study 111-206 on investigational treatment (BMN 111 or placebo).

2. Parent(s) or guardian(s) 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. Also, subjects under the age of majority are willing
and able to provide written assent (if required by local regulations or the IRB/IEC)
after the nature of the study has been explained and prior to performance of any
research-related procedure. Subjects who reach the age of majority in their country
while the study is ongoing will be asked to provide their own written consent again
upon reaching the legal age of majority.

3. Are willing and able to perform all study procedures
Minimum age
15 Months
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Permanently discontinued BMN 111 or placebo prior to completion of Study 111-206

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

3. Require any investigational agent (except BMN 111) prior to completion of study period

4. Current therapy with antihypertensive medications, angiotensin-converting enzyme (ACE)
inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers,
calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, GnRH
agonists, any medication that may impair or enhance compensatory tachycardia,
diuretics, or other drugs known to alter renal or tubular function

5. Pregnant or planning to become pregnant (self or partner) at any time during the study

6. Concurrent disease or condition that, in the view of the investigator, would interfere
with study participation or safety evaluations, for any reason

7. Have a condition or circumstance that, in the view of the investigator, places the
subject at high risk for poor treatment compliance

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
Accrual to date
Final
73
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
Japan
State/province [9] 0 0
Osaka
Country [10] 0 0
Japan
State/province [10] 0 0
Saitama
Country [11] 0 0
Japan
State/province [11] 0 0
Tokushima
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Sheffield

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 2, open-label multi-center long-term extension study, with approximately 70
subjects, to evaluate the safety and efficacy of BMN111 in children with Achondroplasia until
subjects reach near-adult final height. Eligible subjects will have completed 1 year of
BMN111 or placebo treatment in the 111-206 study and once enrolled in the 111-208 extension
study will receive a daily dose of BMN111 by subcutaneous injection according to their age as
determined by 111-206.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03989947
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/ct2/show/NCT03989947