Título: Un estudio multicéntrico de fase 3, aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia y seguridad de la vosoritida en niños con hipocondroplasia

Especialidad: Traumatología

Código de protocolo: 111-303

Número EudraCT: 2024-511234-12-00

Promotor: BioMarin Pharmaceutical Inc.

Investigador principal: Dr. Josep María De Bergua Domingo

Más información:

Criterios de inclusión: Participants must be 3 to < 18 years of age at enrollment.
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.
At least a 6-month period of pre-treatment standing height assessments prior to randomization.
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).
Males and females are eligible to participate in this clinical study.
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.
If sexually active, participants must be willing to use a highly effective method of contraception while participating in the study.
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.
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.

Criterios de exclusión: Short stature condition other than HCH (eg, ACH, trisomy 21, pseudo-achondroplasia).
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 participants short stature, including conditions causing malnutrition (including but not limited to inflammatory bowel disease, cystic fibrosis, celiac disease and eating disorders) e. Autonomic neuropathy
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
Have an unstable condition likely to require surgical intervention during the study.
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.
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.

Centro: Vithas Vitoria