Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of rhASM in Pediatric Patients <18 Years of Age with Acid Sphingomyelinase Deficiency

Phase 1

Conditions: Patients with acid sphingomyelinase deficiency (Niemann-Pick disease)
MedDRA version: 18.0 Level: LLT Classification code 10041515 Term: Sphingomyelin lipidosis System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2014-003198-40-FR

Lead Sponsor: Genzyme Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

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

Exclusion Criteria

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
Timepoint(s) of evaluation of this end point: From screening through week 52;Main Objective: To evaluate the safety and tolerability of recombinant human acid sphingomyelinase (rhASM) administered intravenously in pediatric patients every 2 weeks for 52 weeks;Secondary Objective: To characterize the pharmacokinetic profile and evaluate the pharmacodynamics and exploratory efficacy of rhASM administered intravenously in pediatric patients every 2 weeks for 52 weeks.;<br> Primary end point(s): Number of adverse events<br> Clinically significant changes in laboratory parameters<br> Clinically significant changes in physical examinations<br>

Secondary Outcome Measures

Name	Time	Method

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