An Extension Study to Evaluate the Efficacy and Safety 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

3 Apr 2019 → ongoing

Decision date (initial)

2024-05-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioMarin Pharmaceutical Inc.

External identifiers

EU CT number

2023-508864-31-00

EudraCT number

2017-002404-28

ClinicalTrials.gov

NCT03424018

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Evaluate the long-term safety, tolerability, and efficacy for growth in children with ACH treated with BMN 111

Secondary objectives 8

1. Evaluate the pharmacokinetics of BMN 111
2. Evaluate immunogenicity of BMN 111 and assess impact on safety, PK, and efficacy measures
3. Evaluate body proportion ratios of the extremities
4. Evaluate effect of BMN 111 on bone morphology/quality by X-ray and DXA
5. Evaluate changes in health-related quality of life as measured the Quality of Life in Short Stature Youth (QoLISSY) and the PedsQL questionnaires
6. Evaluate changes in functional independence as measured by the Wee-FIM clinician-reported outcome
7. Evaluate change from baseline in bone metabolism biomarkers
8. 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 5

1. Must have completed Study 111-301
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/IEC) 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. 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
4. If sexually active, are willing to use contraception as specified in section 9.3.3 of the protocol
5. Are willing and able to perform all study procedures

Exclusion criteria 9

1. Permanently discontinued BMN 111 or placebo prior to completion of Study 111-301
2. Have a clinically significant finding or arrhythmia on Baseline electrocardiogram (ECG) that indicates abnormal cardiac function or conduction or QTc-F > 450 msec
3. Evidence of decreased growth velocity (AGV < 1.5 cm/year) as assessed over a period of at least 6 months or of growth plate closure (proximal tibia, distal femur) through bilateral lower extremity X-rays
4. Require any investigational agent prior to completion of study period
5. Current therapy with antihypertensive medications, angiotensin- converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, GnRH agonists, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function (Table 9.3.2.1)
6. Planned or expected to have limb-lengthening surgery during the study period
7. Pregnant or breastfeeding at the Baseline Visit or planning to become pregnant (self or partner) at any time during the study
8. Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason
9. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1)Key efficacy endpoints: a)Change from baseline in AGV b) Change from baseline in height Z-score c)Change from baseline in upper to lower body segment ratio
2. 2)Safety assessments: Incidence, severity, and relationship to study drug of all treatment-emergent adverse events (TEAEs).
3. 3)Procedures/ interventions/ surgeries, imaging assessments, clinical laboratory assessments, Child Behavior Checklist (CBCL), vital signs, electrocardiogram (ECG), and hip clinical assessment.

Secondary endpoints 6

1. Change from baseline in: 1)Upper Arm Length to Lower Arm (Forearm), Length Ratio
2. 2)Upper Leg Length (Thigh) to Knee to Heel Length Ratio
3. 3)Upper Leg Length (Thigh) to Tibial Length Ratio
4. 4)Arm Span to Standing Height Ratio
5. 5)Bone age, bone age Z-score, bone mineral density, (BMD), BMD Z-score, and bone mineral content (BMC)
6. 6)QoLISSY and PedsQL domain and total scores

Investigational products

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

Test 3

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 4

Locations

2 EU/EEA countries · 5 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 32 files

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

Application history

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