We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov 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)

This study is currently recruiting participants.
Verified December 2017 by Sanofi ( Genzyme, a Sanofi Company )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02292654
First Posted: November 17, 2014
Last Update Posted: December 8, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
  Purpose

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 Intervention Phase
Sphingomyelin Lipidosis Drug: Olipudase alfa Phase 1 Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Sanofi ( Genzyme, a Sanofi Company ):

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: From screening through Week 64 ]
  • Clinically significant changes in laboratory parameters (complete blood count (CBC), clinical chemistry, and urinalysis) [ Time Frame: From screening through Week 64 ]
  • 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:
  • Maximum concentration (Cmax) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  • 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 ]
  • 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 ]
  • Half-life (t1/2) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  • Clearance (CL) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  • Volume of distribution (Vss) [ Time Frame: With the first infusion at 0.3, 1.0 and 3.0 mg/kg and at Week 52 ]
  • Change in sphingomyelin levels [ Time Frame: From Day 1 through Week 64 ]
  • Change in sphingomyelin metabolite levels [ Time Frame: From Day 1 through Week 64 ]

Estimated Enrollment: 20
Study Start Date: May 1, 2015
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).
  Eligibility

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.


Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02292654


Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, New York
Investigational Site Number 840001 Recruiting
New York, New York, United States, 10029
Brazil
Investigational Site Number 076001 Active, not recruiting
Porto Alegre, Brazil, 90035 003
France
Investigational Site Number 250002 Recruiting
Bron, France, 69000
Italy
Investigational Site Number 380001 Recruiting
Udine, Italy, 33100
United Kingdom
Investigational Site Number 826001 Recruiting
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT02292654     History of Changes
Other Study ID Numbers: DFI13803
U1111-1160-6469 ( Other Identifier: UTN )
First Submitted: November 7, 2014
First Posted: November 17, 2014
Last Update Posted: December 8, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Lipidoses
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
Sphingolipidoses
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
Histiocytosis
Lymphatic Diseases
Lysosomal Storage Diseases