A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia
Sponsored by BioMarin Pharmaceutical
About this trial
Last updated 5 years ago
Study ID
Status
Type
Phase
Placebo
Accepting
Not accepting
Trial Timing
Ended 8 years ago
What is this trial about?
What are the participation requirements?
Inclusion Criteria
- Parent(s) or guardian(s) are willing and able to provide written, signed informed consent
- 5 to 14 years old at end of study
- ACH, documented by clinical grounds, confirmed by genetic testing
- At least 6-month of pretreatment growth assessment in Study 111-901 before study entry, and one standing height at least 6 months prior to screening for 111-202
- Negative pregnancy test at the Screening Visit for females ≥ 10 years old or who have begun menses
- If sexually active, willing to use a highly effective method of contraception while participating in the study
- Ambulatory, able to stand without assistance
- Willing and able to perform all study procedures as physically possible
- Parents/caregivers willing to administer daily injections to the subjects Additional inclusion Criteria Optional, Open-label Extension Phase:
- Appropriate written informed consent
Exclusion Criteria
- Hypochondroplasia or short stature condition other than ACH
- Have any of the following:
- Unstable condition requiring surgical intervention during the study
- Growth plates have fused
- Have a history of any of the following:
- Have an ECG showing any of the following:
- Documented Vitamin D deficiency
- Require any investigational agent prior to completion of study period
- Have received another investigational product or investigational medical device within 30 days before the Screening visit
- Use of any other investigational product or investigational medical device for the treatment of ACH or short stature
- Current chronic therapy with antihypertensive medications, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function
- Treatment with growth hormone, IGF-1 (Insulin-like growth factor), or anabolic steroids in the previous 6 months or long-term treatment (> 3 months) at any time
- Long-term treatment (> 1 month) with oral corticosteroids
- Concomitant medication that prolongs the QT/QTc-F interval within 14 days or 5 half-lives, whichever is longer, before the Screening visit
- Pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study
- Limb-lengthening or bone-related surgery < 18 months prior to study enrollment
- Had a fracture of the long bones or spine within 6 months prior to screening (except for fracture of digits or toes)
- AST (Aspartate Transaminase) or ALT (Alanine Transaminase) at least 3x upper limit of normal (ULN) or total bilirubin at least 2x ULN
- Evidence of severe sleep apnea requiring surgery or new initiation of CPAP (Continuous positive airway pressure).
- History of malignancy and chemotherapy/radiation or currently under work-up for suspected malignancy
- Known hypersensitivity to BMN 111 or its excipients
- Have a condition or circumstance that, in the view of the Investigator, places the subject at high risk for poor treatment compliance or for not completing the study
- Concurrent disease or condition that would interfere with study participation or safety
- Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant as determined by the PI.
- Have a history of hip surgery or severe hip dysplasia
- Have a 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.
- Are unable to lie flat when in prone position Additional Exclusion Criteria for Optional, Open-label Extension Phase:
- Use of restricted therapies during the initial 6 months of the study
- Permanently discontinued BMN 111 during the initial 6 months of the study