A Long-term Study to Evaluate Safety, Tolerability, and Efficacy of BMN 111 in Children with Achondroplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biomarin Pharmaceutical Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]

Trial duration

10 Feb 2017 → 19 Dec 2024

Decision date (initial)

2024-05-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioMarin Pharmaceutical, Inc.

External identifiers

EU CT number

2023-508754-26-00

EudraCT number

2015-004004-30

ClinicalTrials.gov

NCT02724228

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacodynamic, Others, Pharmacogenomic, Efficacy

Primary Objective:
To evaluate the long-term safety and tolerability of daily SC injections of BMN 111 in children with ACH

Secondary objectives 4

1. To evaluate the effect of BMN 111 on annualized growth velocity
2. To evaluate the effect of BMN 111 on growth parameters
3. 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)
4. To evaluate the effect of BMN 111 on final adult height

Conditions and MedDRA coding

Achondroplasia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 researchrelated procedure. Also, subjects under the age of 18 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 researchrelated procedure.
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 – not applicable in France

Exclusion criteria 6

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety will be evaluated by the incidence of AEs, serious adverse events (SAEs), laboratory test results (urinalysis, chemistry, hematology), changes in vital signs, physical examination, and echocardiogram (ECHO), X-rays/QCT results, and clinical hip assessment.

Secondary endpoints 2

1. Efficacy will be assessed by change from baseline in height growth velocity (annualized to cm/year), height, final adult height, 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.
2. 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. Final adult height defined as the height achieved at 16 years of age for females, and 18 years of age for males.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biomarin Pharmaceutical Inc.

Sponsor organisation

Biomarin Pharmaceutical Inc.

Address

105 Digital Drive

City

Novato

Postcode

94949-8703

Country

United States

Scientific contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

BioMarin Pharmaceutical Inc.

Public contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

BioMarin Pharmaceutical Inc.

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications