E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000452 |
E.1.2 | Term | Achondroplasia |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of daily SC injections of BMN 111 in children with ACH |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the effect of BMN 111 on annualized growth velocity
-To evaluate the effect of BMN 111 on growth parameters
-To evaluate in the effect of BMN 111 on body proportions (upper arm to forearm length, upper leg to lower leg length, and upper to lower body segment ratios)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must have completed 24 months (± 14 days) of BMN 111 treatment in Study 111-202.
2. Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Also, subjects under the age of majority are willing and able to provide written assent (if required by local regulations or the IRB/EC) after the nature of the study has been explained and prior to performance of any research-related procedure. Subjects who reach the age of majority in their country while the study is ongoing will be asked to provide their own written consent again upon reaching the legal age of majority.
3. If sexually active, is willing to use a highly effective method of contraception while participating in the study
4. Females ≥ 10 years old or who have begun menses must have a negative pregnancy test at the Baseline Visit and be willing to have additional pregnancy tests during the study
5. Are willing and able to perform all study procedures as physically possible
6. Caregivers are willing to administer daily injections to the subjects and complete the required training
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E.4 | Principal exclusion criteria |
1. Requires any investigational agent prior to completion of study period
2. 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
3. Concurrent disease or condition that, in the view of the Investigator, would interfere with study participation or safety evaluations for any reason
4. Permanently discontinued BMN 111 during the 111-202 study
5. Subject is pregnant at the Baseline visit or planning to become pregnant (self or partner) at any time during the study
6. Current chronic therapy with any of the following restricted medications:
-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
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be evaluated by the incidence of AEs, SAEs, and clinically significant changes in vital signs, physical examination and ECHO results, imaging, and laboratory test results (urinalysis, chemistry, hematology). Additionally, imaging, hip monitoring, biomarker, and physical measurement data will be utilized for safety-related reviews and analysis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs, SAEs, vital signs, physical exam: Baseline, Day 1, every 26 weeks , until 5 years or NFAH reached, Early Term
ECHO: Baseline, Weeks 130, 260, until 5 years or NFAH reached
Anti-BMN 111 immunogenicity: Baseline, every 26 weeks until 5 years or NFAH reached, Early Term
Lab tests: Baseline, every 26 weeks until 5 years or NFAH reached, Early Term
Hip Monitoring: Baseline, every 26 weeks until 5 years or NFAH reached, Early Term
X-ray (PA of hand and wrist): Baseline, every 52 weeks until 5 years or NFAH reached, Early Term
AP lower extremity radiograph: Baseline, every 2 years starting at week 208 or NFAH reached, Early Term |
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E.5.2 | Secondary end point(s) |
Efficacy will be assessed by change from baseline in height growth velocity (annualized to cm/year), growth parameters, and in body proportions. These changes will be assessed by anthropometric measurements and measurement ratios. Growth parameters (anthropometric measurements) may include but are not limited to height, standing height, sitting height, weight, head circumference, upper and lower arm and leg length, and arm span. Body proportion measurements may include but are not limited to upper: lower body segment ratio, upper arm: forearm length ratio, upper leg: lower leg length ratio, and arm span: standing height ratio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, every 26 weeks until 5 years or NFAH reached, Early Term |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
France |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |