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Trial record 2 of 3 for:    "Acid Sphingomyelinase Deficiency" | "Pharmaceutical Solutions"

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

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ClinicalTrials.gov Identifier: NCT02004691
Recruitment Status : Active, not recruiting
First Posted : December 9, 2013
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE November 26, 2013
First Posted Date  ICMJE December 9, 2013
Last Update Posted Date October 14, 2019
Actual Study Start Date  ICMJE December 18, 2015
Estimated Primary Completion Date October 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2018)
  • Percentage change in spleen volume (combined with change in SRS in the US only, and referred to as "combination spleen endpoint") [ Time Frame: Baseline to Week 52 ]
  • Percentage change in diffusing capacity of the lung for carbon monoxide [ Time Frame: Baseline to Week 52 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2013)
Percentage change in spleen volume [ Time Frame: Baseline to Week 52 ]
Change History Complete list of historical versions of study NCT02004691 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2018)
  • Percentage change in liver volume [ Time Frame: Baseline to Week 52 ]
  • Percentage change in platelet count [ Time Frame: Baseline to Week 52 ]
  • Change in fatigue severity as measured by item 3 of the Brief Fatigue Inventory scale [ Time Frame: Baseline to Week 52 ]
  • Change in pain severity as measured by item 3 of the Brief Pain Inventory scale [ Time Frame: Baseline to Week 52 ]
  • Change in dyspnea severity as measured by the Functional Assessment of Chronic Illness Therapy dyspnea tool [ Time Frame: Baseline to Week 52 ]
  • Change in SRS (except US, where it is part of the primary "combination spleen endpoint") [ Time Frame: Baseline to Week 52 ]
  • Number of adverse events [ Time Frame: Baseline to approximately 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2013)
  • Change in Liver Volume [ Time Frame: Baseline to Week 52 ]
  • Participants with Pulmonary imaging and function tests [ Time Frame: Baseline to Week 52 ]
  • Exercise capacity by cycle ergometry [ Time Frame: Baseline to Week 52 ]
  • Hematology [ Time Frame: Baseline to Week 52 ]
  • Physician Global Assessment [ Time Frame: Baseline to Week 52 ]
  • Efficacy biomarkers [ Time Frame: Baseline to Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
Official Title  ICMJE A Phase 2/3, Multicenter, Randomized, Double-blinded, Placebo-controlled, Repeat-dose Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
Brief Summary

Primary Objective:

The primary objective of this phase 2/3 study is to evaluate the efficacy 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 changes in: 1) spleen volume as measured by abdominal magnetic resonance imaging (MRI) (and, for the United States [US] only, in association with patient perception related to spleen volume as measured by splenomegaly related score [SRS]); and 2) infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide (DLCO).

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 on the patient perception related to spleen volume as measured by the SRS after 52 weeks of study drug administration. (For the US, the effect of olipudase alfa on the splenomegaly related score is part of the primary objective).
  • To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following endpoints assessed sequentially:
  • The effect of olipudase alfa on liver volume;
  • The effect of olipudase alfa on platelet count;
  • The effect of olipudase alfa on fatigue;
  • The effect of olipudase alfa on pain;
  • The effect of olipudase alfa on dyspnea.
Detailed Description The total duration per patient is at least 3 years and up to 5 years and 3 months. This includes up to approximately two month of screening, 52 weeks of primary analysis period, up to 4 years and 3 months of extension treatment period, an end-of- study visit within 2 weeks of the last treatment, and a safety follow-up 30 to 37 days after the last treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Sphingomyelin Lipidosis
Intervention  ICMJE
  • Drug: placebo (saline)

    Pharmaceutical form: solution administered once every two weeks during the 52 weeks of the primary analysis period for patients randomized to placebo.

    Route of administration: intravenous infusion

  • Drug: GZ402665

    Pharmaceutical form: Powder for concentrate for solution for infusion administered once every two weeks during the 52 weeks of the primary analysis period for patients randomized to olipudase alfa, and during the extension treatment period for all patients.

    Route of administration: intravenous infusion

    Other Name: olipudase alfa
Study Arms  ICMJE
  • Experimental: GZ402665
    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 for patients randomized to olipudase alfa, and during the extension treatment period for all patients.
    Intervention: Drug: GZ402665
  • Placebo Comparator: Placebo
    Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to placebo.
    Intervention: Drug: placebo (saline)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2016)
36
Original Estimated Enrollment  ICMJE
 (submitted: December 4, 2013)
15
Estimated Study Completion Date  ICMJE October 2023
Estimated Primary Completion Date October 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 SRS of at least 5.
  • 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 for up to 15 days following their last dose of study drug.

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 (e.g., clinically significant arrhythmia, moderate or severe pulmonary hypertension or clinically significant valve dysfunction, or <40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); malignancy diagnosed within the past 5 years (other than non-melanoma skin cancer), or any other serious medical condition that may preclude participation in the study.
  • The patient has a platelet count <60,000/μL based on the average of 2 samples.
  • 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.

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Bulgaria,   Chile,   France,   Germany,   Italy,   Japan,   Netherlands,   Portugal,   Spain,   Tunisia,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02004691
Other Study ID Numbers  ICMJE DFI12712
2015‐000371‐26 ( EudraCT Number )
U1111-1142-5963 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP