Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of rhASM in Pediatric Patients <18 Years of Age with Acid Sphingomyelinase Deficiency
- Conditions
- MedDRA version: 17.1 Level: LLT Classification code 10041515 Term: Sphingomyelin lipidosis System Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]Patients with acid sphingomyelinase deficiency (Niemann-Pick disease)
- Registration Number
- EUCTR2014-003198-40-IT
- Lead Sponsor
- Genzyme Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
The patient and/or patient’s parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.
The patient is aged 0 to <18 years of age on the date of informed assent/consent.
The patient has documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes.
The patient has a spleen volume =5 multiples of normal (MN) measured by magnetic resonance imaging (MRI); patients who have had partial splenectomy will be allowed if the procedure was performed =1 year before screening and the residual spleen volume is =5 MN.
The patient’s height is -1 Z-score or lower.
A negative serum pregnancy test in female patients of childbearing potential.
Female patients of childbearing potential and sexually active male patients must be willing to practice true abstinence in line with their preferred and usual lifestyle, or use 2 acceptable effective methods of contraception.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
The patient has received an investigational drug within 30 days before study enrollment
The patient has any of the following medical conditions:
- An active, serious, intercurrent illness.
- Active hepatitis B or hepatitis C infection.
- Infection with human immunodeficiency virus (HIV).
- Cirrhosis (determined by clinical evaluation).
- Significant cardiac disease (eg, clinically significant arrhythmia, moderate or severe pulmonary hypertension or valvular dysfunction, or <40% left ventricular ejection fraction by echocardiogram).
- Malignancy diagnosed within the previous 5 years (except basal cell carcinoma).
- Any other extenuating circumstance that can significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
The patient has acute or rapidly progressive neurological abnormalities.
The patients is homozygous for SMPD1 gene mutations R495L, L302P, and fs330 or any combination of these 3 mutations.
The patient has a delay of gross motor skills.
The patient has had a major organ transplant (eg, bone marrow, liver).
The patient requires use of invasive ventilatory support.
The patient requires use of noninvasive ventilatory support while awake and for >12 hours a day.
The patient, in the investigator’s opinion, is unable to adhere to the requirements of the study.
The patient has a platelet count <60,000 /µL (based on the average of 2 screening samples obtained greater than 24 hours apart).
The patient has alanine aminotransferase or aspartate aminotransferase >250 IU/L or total bilirubin>1.5 mg/dL.
The patient has an international normalized ratio (INR) >1.5
The patient is unwilling or unable to abstain from ingesting alcohol the day before through 3 days after each infusion of rhASM during the treatment period. Measuring alcohol concentration in blood is not required.
The patient is scheduled during the study for in-patient hospitalization including elective surgery.
The patient requires medication(s) that may decrease rhASM activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants [eg, imipramine, or desipramine]).
The patient is breast-feeding.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method