A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vosoritide in Children With Hypochondroplasia

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

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

17 Dec 2024 → 24 Apr 2026

Decision date (initial)

2024-09-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioMarin Pharmaceutical Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate the effect of vosoritide on annualized grow velocity (AGV) versus placebo

Secondary objectives 2

1. To evaluate the effect of vosoritide on standing height versus placebo
2. To evaluate the effect of vosoritide on height Z-score versus placebo

Conditions and MedDRA coding

Hypochondroplasia

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002033-PIP02-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participants must be ≥ 3 to < 18 years of age at enrollment.
2. A confirmed genetic diagnosis of HCH, demonstrating evidence of a pathogenic FGFR3 variant associated with HCH, as confirmed by prior genetic testing in Study 111-902.
3. At least a 6-month period of pre-treatment standing height assessments prior to randomization.
4. A height Z score of ≤ − 2.0 SDS in reference to the general population of the same age and sex, as calculated using the Center for Disease Control and Prevention (CDC) growth charts (https://www.cdc.gov/growthcharts/zscore.htm).
5. Males and females are eligible to participate in this clinical study.
6. Females ≥ 10 years old or who have begun menses must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
7. If sexually active, participants must be willing to use a highly effective method of contraception while participating in the study.
8. Participants must be capable of giving signed informed consent as described in Appendix 1 in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
9. Parent(s) or guardian(s) must be willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any study-related procedure. Participants under the age of 18 must be 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 study-related procedure.

Exclusion criteria 6

1. Short stature condition other than HCH (eg, ACH, trisomy 21, pseudo-achondroplasia).
2. Have any of the following documented conditions: a. Hypothyroidism or hyperthyroidism, growth hormone deficiency, hypercortisolism or hypopituitarism, or other endocrine cause of short stature b. Insulin-requiring diabetes mellitus c. Autoimmune inflammatory disease (including but not limited to systemic lupus erythematosus, juvenile dermatomyositis and scleroderma) d. Other chronic diseases that per investigator determination may be causative of a participant’s short stature, including conditions causing malnutrition (including but not limited to inflammatory bowel disease, cystic fibrosis, celiac disease and eating disorders) e. Autonomic neuropathy
3. Have any of the following documented conditions: a. Renal insufficiency defined as an estimated glomerular filtration rate (eGFR) of < 60 ml/min/ 1.73 m2 using the revised Schwartz Pediatric Bedside eGFR formula (Schwartz 2009). b. Chronic anemia (hemoglobin < 10 g/dl. Note: participants with hemoglobin below the indicated threshold may receive treatment for anemia and re-screen after 8 weeks. c. Recurrent symptomatic hypotension (defined as episodes of low blood pressure generally accompanied by symptoms ie, dizziness, fainting, postural tachycardia) or recurrent symptomatic orthostatic hypotension. d. History of clinically significant cardiac or vascular disease as judged by the Investigator, including but not limited to the following: i. Cardiac dysfunction ii. Hypertrophic cardiomyopathy iii. Pulmonary hypertension iv. Congenital heart disease v. Cerebrovascular disease vi. Aortic insufficiency or other clinically significant valvular dysfunction vii. Clinically significant atrial or ventricular arrhythmias
4. Have an unstable condition likely to require surgical intervention during the study.
5. Evidence of decreased growth velocity (AGV < 1.5 cm/year) as assessed over a period of at least 6 months and/or growth plate closure assessed using left hand antero posterior (AP) X-rays, by the Greulich and Pyle method (Greulich 1971) as per standard of care.
6. Vitamin D deficiency (concentration of blood 25-hydroxy-vitamin D < 12 ng/ml or < 30 nmol/L) at Screening. Note: participants with blood 25-hydroxy-vitamin D below the indicated threshold may receive supplementation and re-screen after 8 weeks.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in AGV at Week 52

Secondary endpoints 2

1. Change from baseline in standing height at Week 52 versus placebo
2. Change from baseline in height Z-score at Week 52 versus placebo

Investigational products

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

Test 2

Placebo 1

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 14

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 63 files

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

Application history

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