Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency (ASCEND)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2015 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT02004691
First received: November 26, 2013
Last updated: April 15, 2015
Last verified: April 2015
  Purpose

Primary Objective:

The primary objective of this phase 2/3 study is to evaluate the efficacy of different doses of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult patients with acid sphingomyelinase deficiency (ASMD) by assessing separately, changes in spleen volume as measured by abdominal magnetic resonance imaging (MRI) and infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide.

Secondary Objectives:

To confirm the safety of olipudase alfa administered intravenously once every 2 weeks for 52 weeks.

To characterize the effect of olipudase alfa after 52 weeks of study drug administration on a symptom-based composite score composed of 4 symptom domains (pain, fatigue, dyspnea, and abdominal complaints).

To characterize the effect of olipudase alfa on the splenomegaly-related symptom score after 52 weeks of study drug administration.

To characterize the effect of olipudase alfa on liver volume after 52 weeks of study drug administration.

To characterize the effect of olipudase alfa on platelet count after 52 weeks of study drug administration.


Condition Intervention Phase
Sphingomyelin Lipidosis
Drug: placebo (saline)
Drug: GZ402665
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Multicenter, Randomized, Double-blinded, Placebo-controlled, Repeat-dose, Dose-comparison Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage change in spleen volume [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Percentage change in diffusing capacity of the lung for carbon monoxide [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in symptom-based composite score composed of 4 symptom domains (pain, fatigue, dyspnea, and abdominal complaints) [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Change in splenomegaly-related symptom score [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Percentage change in liver volume [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Percentage change in platelet count [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Number of adverse events [ Time Frame: Baseline to approximately 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 35
Study Start Date: August 2015
Estimated Study Completion Date: March 2022
Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GZ402665 Dose 1
Olipudase alfa dose (1 mg/kg body weight) in saline administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period
Drug: GZ402665

Pharmaceutical form: Powder for concentrate for solution for infusion

Route of administration: intravenous infusion

Other Name: olipudase alfa
Experimental: GZ402665 Dose 2
Olipudase alfa dose (3 mg/kg body weight) in saline administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period
Drug: GZ402665

Pharmaceutical form: Powder for concentrate for solution for infusion

Route of administration: intravenous infusion

Other Name: olipudase alfa
Placebo Comparator: Placebo
Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period
Drug: placebo (saline)

Pharmaceutical form: solution

Route of administration: intravenous infusion


Detailed Description:

Up to two month screening + 52 weeks of primary analysis period + up to 4 years of extension treatment period + 30 to 37 days post study safety follow up.

The study will be divided into 2 consecutive major periods: 1) a randomized placebo-controlled, double-blinded primary analysis period (PAP) from day -60 to week 52, which will be followed by 2) an extension treatment period (ETP) that will last up to 4 years. Initially, the ETP will be double-blinded as patients in the placebo arm of the PAP are randomized to active treatment with a target dose of either 1 mg/kg or 3 mg/kg.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • Female patients of childbearing potential must have a negative serum pregnancy test for beta-human chorionic gonadotropin (β-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.

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 basal cell carcinoma), or any other extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
  • The patient has a platelet count <60,000/μL (based on the average of 2 samples obtained at least 12 hours but no longer than 24 hours apart).
  • 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 that are required at screening/baseline and at Week 52, 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.

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

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02004691

Contacts
Contact: Trial Transparency Team Contact-US@sanofi.com

Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT02004691     History of Changes
Other Study ID Numbers: DFI12712, 2015‐000371‐26, U1111-1142-5963
Study First Received: November 26, 2013
Last Updated: April 15, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Niemann-Pick Diseases
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Lymphatic Diseases
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Nervous System Diseases
Histiocytosis
Histiocytosis, Non-Langerhans-Cell
Lipid Metabolism, Inborn Errors
Lipidoses
Metabolism, Inborn Errors
Sphingolipidoses

ClinicalTrials.gov processed this record on May 26, 2015