Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients with Acid Sphingomyelinase Deficiency

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]; Patients with acid sphingomyelinase deficiency (Niemann-Pick Type B disease); MedDRA version: 20.1Level: LLTClassification code 10041515Term: Sphingomyelin lipidosisSystem Organ Class: 100000004850

• Registration Number: EUCTR2015-000371-26-PT
• Lead Sponsor: Genzyme Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09-08
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

The patient is willing and able to provide signed written informed consent.
The patient is male or female aged 18 years or older.
The patient has documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; and a clinical diagnosis consistent with Niemann-Pick disease type B (NPD B).
The patient has diffuse capacity of the lung for carbon monoxide =70% of the predicted normal value.
The patient has a spleen volume =6 multiples of normal (MN) measured by MRI; patients who have had partial splenectomy will be allowed if the procedure was performed =1 year before screening/baseline and the residual spleen volume is =6 MN.
The patient has a mean splenomegaly-related symptom score of at least 5.
Female patients of childbearing potential must have a negative serum pregnancy test for beta-human chorionic gonadotropin (ß-HCG).
Female patients of childbearing potential and 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 for up to 15 days following their last dose of study drug.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

The patient has received an investigational drug within 30 days before study enrollment.
The patient has a medical condition, including significant intercurrent illness; significant cardiac disease (eg, clinically significant arrhythmia, moderate or severe pulmonary hypertension or valvular dysfunction, or <40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); cirrhosis (as determined by clinical evaluation or liver biopsy); malignancy diagnosed within the past 5 years (other than nonmelanoma
skin cancer), or any other serious medical condition that may
preclude participation in the study.
The patient has a platelet count <60,000/µL
The patient has an international normalized ratio (INR) >1.5.
The patient has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL (except for patients with Gilbert's syndrome).
The patient has had a major organ transplant (eg, bone marrow or liver).
The patient is scheduled during the study for in-patient hospitalization including elective surgery and excluding the liver biopsies required per protocol.
The patient, in the opinion of the investigator, is unable to adhere to the requirements of the study.
The patient is unwilling or unable to abstain from the use of alcohol for 1 day before and 3 days after each study drug infusion. Testing for blood alcohol levels will not be required.
The patient is unwilling or unable to avoid 10 days before and 3 days after the protocol scheduled liver biopsies the use of medications or herbal supplements that are potentially hepatotoxic (eg, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, anti-depressants, kava, echinacea) and/or may cause or prolong bleeding (eg, anti-coagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng).
The patient requires medications that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine, tricyclic antidepressants [eg, imipramine, or desipramine]).
The patient requires use of invasive ventilatory support.
The patient requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
The patient is breast-feeding.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified