AchondroplasiaPhase 3NCT03197766
A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
A Phase 3 study testing BMN 111 in people with Achondroplasia, run by BioMarin Pharmaceutical at 24 sites in 7 countries.
Trial summary
The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for the treatment of children with Achondroplasia. Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Achondroplasia
- What is being tested?
- BMN 111
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 121 participants
- Where
- 24 sitesin 7 countries
- Study dates
- 12 Dec 2016to 30 Oct 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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
Trial locations and contacts
24 sites in 7 countries.
24 sites in 7 countries
United States11 sites
Johns Hopkins University
Baltimore, Maryland, 21287
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Missouri
Columbia, Missouri, 65201
Emory University
Decatur, Georgia, 30033
Baylor College of Medicine
Houston, Texas, 77030
Medical College of Wisconsin, Children's Hospital
Milwaukee, Wisconsin, 53226
Children's Hospital & Research Center Oakland
Oakland, California, 94609
Seattle Children's Hospital
Seattle, Washington, 98105
Harbor - UCLA Medical Center
Torrance, California, 90509
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
Japan3 sites
Osaka University Hospital
Osaka
Saitama Children's Medical Center
Saitama
Tokushima University Hospital
Tokushima
Spain3 sites
Institut Catala de Traumatologica I Medicina de l'Esport
Barcelona, 08028
Hospital Sant Joan de Deu
Barcelona, 08950
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Australia2 sites
Murdoch Children's Research Institute
Parkville, Victoria, 3052
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Germany2 sites
Otto-von-Guericke Universitaet, Universitaetskinderklinik
Magdeburg, 39120
Universitätsklinikum Münster
Münster, 48149
United Kingdom2 sites
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
London, SE1 9RT
Sheffield Children's NHS Foundation Trust
Sheffield, S10 2TH
Turkey (Türkiye)1 site
Acibadem University School of Medicine
Istanbul, 34752
About this study
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
The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for the treatment of children with Achondroplasia.
Read the detailed description
This is a Phase 3 randomized, placebo-controlled, double-blind multicenter study with approximately 110 subjects, aged 5 to < 18 years old. Subjects with documented Achondroplasia confirmed by genetic testing will have been enrolled in Study 111-901 for at least a 6-month period immediately before entering into the 111-301 study. Eligible subjects will be randomly assigned to one of two treatment groups: placebo or BMN 111 at 15 μg/kg. The route of administration is subcutaneous injection and the frequency is daily.
- Conditions
- Achondroplasia
- Being tested
- BMN 111, Placebo
- Keywords
- 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
- Medical subject headings
- Achondroplasia, Dwarfism, Bone Diseases, Bone Diseases, Developmental, Musculoskeletal Diseases, Genetic Diseases, Inborn, Osteochondrodysplasias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMN 111Drug
Also called Vosoritide, Modified recombinant human C-type natriuretic peptide
Subcutaneous injection of 15 μg/kg of BMN 111 daily
PlaceboDrug
Subcutaneous injection of 15 μg/kg of placebo daily
| Study group | Role | What they receive |
|---|---|---|
| Active BMN 111 | Experimental | Daily subcutaneous injection of 15 micrograms per kilogram BMN111 Receives: Drug: BMN 111 |
| Placebo | Placebo comparator | Daily subcutaneous injection of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Annualized Growth Velocity (AGV) at 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
Measured: At Baseline and Week 52
Secondary outcomes (3)
Change From Baseline in Height Z-score at 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.
Measured: At baseline and Week 52
Change From Baseline in Upper to Lower Segment Body Ratio at 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
Measured: At baseline and Week 52
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment
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)
Measured: Up to Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2017
- Study start12 Dec 2016
- Primary completion30 Oct 2019
- Study completion30 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AchondroplasiaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03197766
- Sponsor's protocol ID
- 111-301
- Other IDs
- 2015-003836-11, 2015
- Status last verified
- Feb 2022
- First submitted
- 23 May 2017
- Last updated
- 2 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Palm K, Prada CE, Kubota T, Arundel P, Kotani Y, Leiva-Gea A, Bober MB, Hecht JT, Legare JM, Lawrinson S, Low A, Sabir I, Huntsman-Labed A, Day JRS. Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study. Med. 2025 May 9;6(5):100566. doi: 10.1016/j.medj.2024.11.019. Epub 2024 Dec 30.
PubMed 39740666Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Mohnike K, Prada CE, Kubota T, Arundel P, Leiva-Gea A, Rowell R, Low A, Sabir I, Huntsman-Labed A, Day J. Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life. Genet Med. 2024 Dec;26(12):101274. doi: 10.1016/j.gim.2024.101274. Epub 2024 Sep 18.
PubMed 39305160Qi Y, Chan ML, Mould DR, Larimore K, Fisheleva E, Cherukuri A, Day J, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Bober MB, Henshaw J. Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model. Clin Pharmacokinet. 2024 May;63(5):707-719. doi: 10.1007/s40262-024-01371-6. Epub 2024 Apr 23.
PubMed 38649657Chan ML, Qi Y, Larimore K, Cherukuri A, Seid L, Jayaram K, Jeha G, Fisheleva E, Day J, Huntsman-Labed A, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Horton WA, Henshaw J. Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Clin Pharmacokinet. 2022 Feb;61(2):263-280. doi: 10.1007/s40262-021-01059-1. Epub 2021 Aug 25.
PubMed 34431071
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03197766
- Acronym / sponsor ID
- 111-301
- Conditions
- Achondroplasia
- Keywords
- Achondroplasia, Dwarfism, Bone Diseases, Bone Diseases, Developmental, ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases, Natriuretic Agents
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 12 Dec 2016 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 30 Oct 2019 (actual)
- First posted
- 23 Jun 2017 (actual)
- Results
- Posted 2 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for the treatment of children with Achondroplasia.
Detailed description
This is a Phase 3 randomized, placebo-controlled, double-blind multicenter study with approximately 110 subjects, aged 5 to < 18 years old. Subjects with documented Achondroplasia confirmed by genetic testing will have been enrolled in Study 111-901 for at least a 6-month period immediately before entering into the 111-301 study. Eligible subjects will be randomly assigned to one of two treatment groups: placebo or BMN 111 at 15 μg/kg. The route of administration is subcutaneous injection and the frequency is daily.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active BMN 111 | Experimental | Drug: BMN 111Daily subcutaneous injection of 15 micrograms per kilogram BMN111 |
| Placebo | Placebo comparator | Drug: PlaceboDaily subcutaneous injection of placebo |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (28 listed)
- Hypochondroplasia or short stature condition other than ACH
- Have any of the following:
- History of any of the following:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMN 111Also: Vosoritide, Modified recombinant human C-type natriuretic peptideSubcutaneous injection of 15 μg/kg of BMN 111 daily | Drug | Active BMN 111 |
| PlaceboSubcutaneous injection of 15 μg/kg of placebo daily | Drug | Placebo |
Primary outcome
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
3 secondary outcomes
Change From Baseline in Height Z-score at Week 52
Time frame: At baseline and Week 52
Change From Baseline in Upper to Lower Segment Body Ratio at Week 52
Time frame: At baseline and Week 52
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment
Time frame: Up to Week 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39740666Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Palm K, Prada CE, Kubota T, Arundel P, Kotani Y, Leiva-Gea A, Bober MB, Hecht JT, Legare JM, Lawrinson S, Low A, Sabir I, Huntsman-Labed A, Day JRS. Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study. Med. 2025 May 9;6(5):100566. doi: 10.1016/j.medj.2024.11.019. Epub 2024 Dec 30.
- Derived from this study: PubMed 39305160Savarirayan R, Irving M, Wilcox WR, Bacino CA, Hoover-Fong JE, Harmatz P, Polgreen LE, Mohnike K, Prada CE, Kubota T, Arundel P, Leiva-Gea A, Rowell R, Low A, Sabir I, Huntsman-Labed A, Day J. Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life. Genet Med. 2024 Dec;26(12):101274. doi: 10.1016/j.gim.2024.101274. Epub 2024 Sep 18.
- Derived from this study: PubMed 38649657Qi Y, Chan ML, Mould DR, Larimore K, Fisheleva E, Cherukuri A, Day J, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Bober MB, Henshaw J. Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model. Clin Pharmacokinet. 2024 May;63(5):707-719. doi: 10.1007/s40262-024-01371-6. Epub 2024 Apr 23.
- Derived from this study: PubMed 34431071Chan ML, Qi Y, Larimore K, Cherukuri A, Seid L, Jayaram K, Jeha G, Fisheleva E, Day J, Huntsman-Labed A, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Horton WA, Henshaw J. Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Clin Pharmacokinet. 2022 Feb;61(2):263-280. doi: 10.1007/s40262-021-01059-1. Epub 2021 Aug 25.
- NIH Genetics Home Reference related topics: AchondroplasiaLink provided by the sponsor.
- NIH Genetic and Rare Diseases Information Center resources: AchondroplasiaLink provided by the sponsor.
- U.S. FDA ResourcesLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director, MD study director
BioMarin Pharmaceutical
24 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BMN 111 in people with Achondroplasia, run by BioMarin Pharmaceutical at 24 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Japan, Spain, Australia, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 (time frame: At Baseline and Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03197766, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.