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

• Register: ClinicalTrials.gov
• Last refreshed on: 9 January 2023
• Main ID: NCT03583697
• Date of registration: 14/06/2018
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• 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
• Date of first enrolment: May 23, 2018
• Target sample size: 75
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03583697
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia, Japan, United Kingdom, United States

Contacts

• Name: Medical Director, MD
• Affiliation: BioMarin Pharmaceutical

Key inclusion & exclusion criteria

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:

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



Age minimum: N/A
Age maximum: 59 Months
Gender: All

Health Condition(s) or Problem(s) studied

Achondroplasia

Intervention(s)

Drug: Placebo

Drug: BMN 111

Primary Outcome(s)

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

Secondary Outcome(s)

Characterize maximum concentration (Cmax) of BMN 111 in plasma [Time Frame: One year]

Evaluate the effect of BMN 111 on growth parameters and body proportions, including change from baseline in upper:lower segment body ratio [Time Frame: One year]

Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [Time Frame: 52 weeks]

Characterize the apparent clearance of drug [Time Frame: 52 weeks]

Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth [Time Frame: One year]

BMN 111 activity will be assessed by measuring bone and collagen metabolism [Time Frame: One year]

Evaluate the effect of BMN 111 on change from baseline in AGV [Time Frame: One year]

Evaluate the effect of BMN 111 on bone morphology/quality by X-ray and dual X-ray absorptiometry (DXA) [Time Frame: One year]

Evaluate the effect of BMN 111 on Sleep study scores by polysomnography [Time Frame: One year]

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time Frame: One year]

Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [Time Frame: 52 weeks]

Characterize the area under the plasma concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [Time Frame: 52 Weeks]

Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8) [Time Frame: One year]

Characterize the elimination half-life of BMN 111 (t½) [Time Frame: 52 weeks]

Secondary ID(s)

2016-003826-18

111-206

Source(s) of Monetary Support

Please refer to primary and secondary sponsors