A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
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| ClinicalTrials.gov Identifier: NCT03197766 |
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Recruitment Status :
Completed
First Posted : June 23, 2017
Results First Posted : March 2, 2022
Last Update Posted : March 2, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Achondroplasia | Drug: BMN 111 Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 121 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia |
| Actual Study Start Date : | December 12, 2016 |
| Actual Primary Completion Date : | October 30, 2019 |
| Actual Study Completion Date : | October 30, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Active BMN 111
Daily subcutaneous injection of 15 micrograms per kilogram BMN111
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Drug: BMN 111
Subcutaneous injection of 15 μg/kg of BMN 111 daily
Other Names:
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Placebo Comparator: Placebo
Daily subcutaneous injection of placebo
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Drug: Placebo
Subcutaneous injection of 15 μg/kg of placebo daily |
- Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 [ Time Frame: At Baseline and Week 52 ]
AGV at a Post-baseline Visit is defined as [(Height at Post-baseline Visit - Height at Baseline)/(Date of Post-baseline Visit - Date of Baseline Assessment)] x 365.25
AGV at Baseline is defined as [(Height at Baseline - last height measurement in Study 111-901 at least 6 months prior to Baseline)/(Date of Baseline Assessment - Date of last height measurement in Study 111-901 at least 6 months prior to Baseline)] x 365.25
- Change From Baseline in Height Z-score at Week 52 [ Time Frame: At baseline and Week 52 ]
Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention.
A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age.
A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age.
To conclude if the height Z score increases then this means the height deficit has decreased.
- Change From Baseline in Upper to Lower Segment Body Ratio at Week 52 [ Time Frame: At baseline and Week 52 ]Evaluate change from baseline in mean upper:lower segment body ratio in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks
- Summary of Subjects Experiencing Adverse Events (AEs) During Treatment [ Time Frame: Up to Week 56 ]
AEs with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included.
serious adverse event (SAE)
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| Ages Eligible for Study: | 5 Years to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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Have any of the following:
- Hypothyroidism or hyperthyroidism
- Insulin-requiring diabetes mellitus
- Autoimmune inflammatory disease
- Inflammatory bowel disease
- Autonomic neuropathy
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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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03197766
Show 24 study locations
| Study Director: | Medical Director, MD | BioMarin Pharmaceutical |
Documents provided by BioMarin Pharmaceutical:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | BioMarin Pharmaceutical |
| ClinicalTrials.gov Identifier: | NCT03197766 |
| Other Study ID Numbers: |
111-301 2015-003836-11 ( EudraCT Number ) |
| First Posted: | June 23, 2017 Key Record Dates |
| Results First Posted: | March 2, 2022 |
| Last Update Posted: | March 2, 2022 |
| Last Verified: | February 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Device Product: | No |
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Achondroplasia Dwarfism Bone Diseases Bone Diseases, Developmental ACH Natriuretic Peptide, C-Type |
Musculoskeletal Diseases Natriuretic Agents Physiological Effects of Drugs Skeletal Dysplasias Genetic Diseases, Inborn Osteochondrodysplasias |
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Achondroplasia Dwarfism Bone Diseases, Developmental Bone Diseases Musculoskeletal Diseases |
Osteochondrodysplasias Genetic Diseases, Inborn Natriuretic Peptide, C-Type Natriuretic Agents Physiological Effects of Drugs |