A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03197766
• Date of registration: 23/05/2017
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• Public title: A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
• Scientific title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
• Date of first enrolment: December 12, 2016
• Target sample size: 121
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03197766
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Germany, Japan, Spain, Turkey, United Kingdom, United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria

- Parent(s) or guardian(s) consent

- 5 to < 18 years old

- ACH, documented and confirmed by genetic testing

- At least a 6-month period of pretreatment growth assessment in Study 111-901 before
study entry

- If sexually active, willing to use a highly effective method of contraception

- Ambulatory and able to stand without assistance

Exclusion criteria:

- Hypochondroplasia or short stature condition other than ACH

- Have any of the following:

- Hypothyroidism or hyperthyroidism

- Insulin-requiring diabetes mellitus

- Autoimmune inflammatory disease

- Inflammatory bowel disease

- Autonomic neuropathy

- History of any of the following:

- Renal insufficiency defined as serum creatinine > 2 mg/dL

- Chronic anemia

- Baseline systolic blood pressure (BP) < 70 millimeters of mercury (mm Hg) or
recurrent symptomatic hypotension (defined as episodes of low BP generally
accompanied by symptoms ie, dizziness, fainting) or recurrent symptomatic
orthostatic hypotension

- Cardiac or vascular disease

- Have a clinically significant finding or arrhythmia on screening
electrocardiogram (ECG) that indicates abnormal cardiac function or
conduction or Fridericias corrected QTc-F > 450 msec

- Have an unstable condition likely to require surgical intervention during the study
(including progressive cervical medullary compression or severe untreated sleep apnea)

- Decreased growth velocity (< 1.5 cm/yr) over a period of 6 months or evidence of
growth plate closure (proximal tibia, distal femur)

- Treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic
steroids in the previous 6 months or treatment greater than 6 months at any time

- Greater than 1 month treatment with oral corticosteroids (low-dose ongoing inhaled
steroid for asthma, or intranasal steroids, are acceptable) in the previous 12 months

- Planned or expected to have limb-lengthening surgery during the study period. Subjects
with previous limb- lengthening surgery may enroll if surgery occurred at least 18
months prior to the study and healing is complete without sequelae.

- Planned or expected bone-related surgery (ie. surgery involving disruption of bone
cortex, excluding tooth extraction), during the study period. Subjects with previous
bone-related surgery may enroll if surgery occurred at least 6 months prior to the
study and healing is complete without sequelae.

- Had a fracture of the long bones or spine within 6 months prior to screening

- History of severe untreated sleep apnea

- New initiation of sleep apnea treatment (e.g. CPAP or sleep apnea-mitigating surgery)
in the previous 2 months prior to screening

- History of hip surgery or hip dysplasia atypical for achondroplastic subjects

- History of clinically significant hip injury in the 30 days prior to screening

- History of slipped capital femoral epiphysis or avascular necrosis of the femoral head

- Abnormal findings on baseline clinical hip exam or imaging assessments that are
determined to be clinically significant

- Concurrent disease or condition that would interfere with study participation or
safety evaluations, for any reason

- Condition or circumstance that places the subject at high risk for poor treatment
compliance or for not completing the study



Age minimum: 5 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Achondroplasia

Intervention(s)

Drug: Placebo

Drug: BMN 111

Primary Outcome(s)

Change from baseline in mean Annualized Growth Velocity [Time Frame: one year]

Secondary Outcome(s)

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

Potential changes in health-related quality of life as measured by the Quality of Life in Short-Statured Youth questionnaire [Time Frame: Screening, weeks 26 and 52]

Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-8) [Time Frame: 52 weeks]

Potential changes in daily activity performance as measured by Activities of Daily Living questionnaire [Time Frame: Screening, weeks 26 and 52]

Change from baseline in body proportion ratios of the extremities in subjects [Time Frame: one year]

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

Change from baseline in height Z-scores [Time Frame: one year]

Characterize maximum concentration (Cmax) of BMN 111 in plasma [Time Frame: 52 weeks]

Incidence of Adverse Events [Safety and Tolerability] [Time Frame: 54 weeks]

Change from baseline in upper to lower segment body ratio [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]

Effect of BMN 111 on bone morphology and quality [Time Frame: Screening, weeks 26 and 52]

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

Secondary ID(s)

2015-003836-11

111-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors