Clinical trial NCT04554940: A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Achondroplasia
Keywords: Dwarfism
Bone Diseases
Bone Diseases, Developmental ACH
Natriuretic Peptide, C-Type
Musculoskeletal Diseases
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2020-09-18
Enrollment: 20
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Through Week 260
Secondary outcomes:
measure: Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software
timeFrame: Through Week 260
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: London
country: United Kingdom
facility: Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's NHS Foundation Trust
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: 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.