Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04554940




Registration number
NCT04554940
Ethics application status
Date submitted
14/09/2020
Date registered
18/09/2020
Date last updated
9/10/2024

Titles & IDs
Public title
A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia
Scientific title
A Randomized, Controlled, Open-label Clinical Trial With an Open-label Extension to Investigate the Safety of Vosoritide in Infants and Young Children With Achondroplasia at Risk of Requiring Cervicomedullary Decompression Surgery
Secondary ID [1] 0 0
111-209
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: Other - vosoritide

Experimental: Vosoritide + Standard of Care - Standard of Care treatment for cervicomedullary compression and once daily subcutaneous injection of recommended dose of vosoritide based on weight-band dosing.

No intervention: Standard of Care Alone - Institutional standard of care monitoring and treatment for cervicomedullary compression


Treatment: Other: vosoritide
Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Timepoint [1] 0 0
Through Week 260
Secondary outcome [1] 0 0
Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software
Timepoint [1] 0 0
Through Week 260

Eligibility
Key inclusion criteria
* 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.
* Have ACH, documented by genetic testing.
* Are willing and able to perform all study procedures as physically possible.
* Age 0 to = 12 months, at study entry (Day 1). Given that any potential impact of vosoritide therapy on the foramen magnum is dependent on treating as early as possible and as long as possible while the synchondroses at the base of the skull are still open. For subjects > 6 months of age at enrollment, a discussion between the investigator and the Medical Monitor should occur with the goal of limiting the number of subjects in the range of > 6 months to = 12 months of age.
* Parent(s) or caregiver(s) are willing to administer daily injections to the subject and complete the required training.
* Have evidence of CMC that "may" require surgical intervention
Minimum age
0 Months
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have hypochondroplasia or short-stature condition other than achondroplasia (eg, trisomy 21, pseudoachondroplasia, etc).
* 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 .
* Have any of the following: Untreated congenital hypothyroidism or maternal history of hyperthyroidism, Insulin-requiring neonatal diabetes mellitus, Autoimmune inflammatory disease, Inflammatory bowel disease, Autonomic neuropathy.
* Have a history of any of the following:Renal insufficiency, Chronic anemia,Baseline 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) and Cardiac or vascular disease.
* Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F = 450 msec on screening ECG.
* 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.
* Have ever had prior cervicomedullary decompression surgery.
* Have had a fracture of the long bones or spine 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
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
10/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
London
Country [2] 0 0
United Kingdom
State/province [2] 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 111-209 is a Phase 2 randomized, open-label clinical trial of BMN 111 in infants and young children with a diagnosis of Achondroplasia at a heightened risk of requiring cervicomedullary decompression surgery
Trial website
https://clinicaltrials.gov/study/NCT04554940
Trial related presentations / publications
Savarirayan R, Irving M, Maixner W, Thompson D, Offiah AC, Connolly DJ, Raghavan A, Powell J, Kronhardt M, Jeha G, Ghani S, Fisheleva E, Day JR. Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery. Sci Prog. 2021 Jan-Mar;104(1):368504211003782. doi: 10.1177/00368504211003782.
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/study/NCT04554940