COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu
Trial record 1 of 1 for:    NCT02292654
Previous Study | Return to List | Next Study

Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency (ASCEND-Peds)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02292654
Recruitment Status : Completed
First Posted : November 17, 2014
Last Update Posted : January 10, 2020
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Brief Summary:

Primary Objective:

To evaluate the safety and tolerability of olipudase alfa 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 olipudase alfa administered intravenously in pediatric patients every 2 weeks for 52 weeks.

Condition or disease Intervention/treatment Phase
Sphingomyelin Lipidosis Drug: Olipudase alfa Phase 1 Phase 2

Detailed Description:
The maximum study duration per patient is approximately 18 months (screening period: up to 60 days; treatment period: 64 weeks; post-treatment period: up to 37 days, not applicable if patient enrolls in a long term extension treatment trial).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Multi-Center, Open-Label, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of Olipudase Alfa in Pediatric Patients Aged <18 Years With Acid Sphingomyelinase Deficiency
Actual Study Start Date : May 1, 2015
Actual Primary Completion Date : December 9, 2019
Actual Study Completion Date : December 9, 2019

Arm Intervention/treatment
Experimental: GZ402665
Olipudase alfa, dose (up to 3.0 mg/kg body weight) once every 2 weeks for 64 weeks
Drug: Olipudase alfa
Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous infusion
Other Name: GZ402665

Primary Outcome Measures :
  1. Number of adverse events [ Time Frame: From screening through Week 64 ]
  2. Clinically significant changes in laboratory parameters (complete blood count (CBC), clinical chemistry, and urinalysis) [ Time Frame: From screening through Week 64 ]
  3. Clinically significant changes in physical examinations (vital signs, electrocardiogram (ECG), doppler echocardiography, and liver ultrasound doppler) [ Time Frame: From screening through Week 64 ]

Secondary Outcome Measures :
  1. Maximum concentration (Cmax) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  2. Area under the curve until the last measurable concentration (AUClast) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  3. Area under the curve extrapolated to infinity (AUC) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  4. Half-life (t1/2) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  5. Clearance (CL) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  6. Volume of distribution (Vss) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  7. Change in sphingomyelin levels [ Time Frame: From Day 1 through Week 64 ]
  8. Change in sphingomyelin metabolite levels [ Time Frame: From Day 1 through Week 64 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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.

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 R496L, 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 × 10^3/µL (based on the average of 2 screening samples obtained up to 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 olipudase alfa 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 can decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants [eg, imipramine, or desipramine]).
  • The patient is breast-feeding.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02292654

Layout table for location information
United States, New York
Investigational Site Number 840001
New York, New York, United States, 10029
Investigational Site Number 076001
Porto Alegre, Brazil, 90035 003
Investigational Site Number 250002
Bron Cedex, France, 69677
Investigational Site Number 276001
Mainz, Germany, 55131
Investigational Site Number 380001
Udine, Italy, 33100
United Kingdom
Investigational Site Number 826001
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Genzyme, a Sanofi Company
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
Layout table for additonal information
Responsible Party: Genzyme, a Sanofi Company Identifier: NCT02292654    
Other Study ID Numbers: DFI13803
U1111-1160-6469 ( Other Identifier: UTN )
First Posted: November 17, 2014    Key Record Dates
Last Update Posted: January 10, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Niemann-Pick Disease, Type A
Niemann-Pick Diseases
Niemann-Pick Disease, Type C
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Metabolic Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases
Lysosomal Storage Diseases